Indole and azaindole inhibitors of pad enzymes

Abstract

The present invention provides compounds of Formula (I) useful as inhibitors of PAD4, compositions thereof, and methods of treating PAD4-related disorders, wherein each of Ring A, L, Q, R1, R2, R3, R4, R7, and R8 along with other variables are as defined herein. ##STR00001##

Claims

1. A compound of Formula (I): ##STR01302## or a pharmaceutically acceptable salt thereof, wherein: Q is selected from N and CH; Ring A is 4- to 15-membered heterocyclyl substituted with 1-4 R.sub.7; R.sub.1 is selected from CH.sub.3, CD.sub.3, and —CH.sub.2-5 membered heterocyclyl comprising carbon atoms and 1-3 heteroatoms selected from N, NC.sub.1-4alkyl, O, and S; R.sub.2 is selected from H, C.sub.1-3 alkyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r—C.sub.3-6 cycloalkyl substituted with 0-5 R.sub.e; R.sub.3 is selected from H, F, Cl, Br, —OR.sub.b, and C.sub.1-3 alkyl substituted with 0-5 R.sub.e; L is absent or selected from —NR.sub.d—, —O—, —C(═O)NR.sub.d—, and —S(O).sub.p—; R.sub.4 is selected from —(CH.sub.2).sub.r-aryl substituted with 1-7 R.sub.5, —(CH.sub.2).sub.r—C.sub.3-12 cycloalkyl (substituted with 1-2 OR.sub.b, C(═O)OR.sub.b, —C(═O)NR.sub.aR.sub.a, —NR.sub.aC(═O)R.sub.b), —(CH.sub.2).sub.r-heterocyclyl comprising carbon atoms and 1-3 heteroatoms selected from N, NR.sub.6, O, and S and substituted with 1-7 R.sub.5; R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, CN, ═O, nitro, C.sub.1-4alkyl substituted with 0-5 R.sub.e, C.sub.2-4alkenyl substituted with 0-5 R.sub.e, C.sub.2-4alkynyl substituted with 0-5 R.sub.e, —(CHR.sub.d).sub.rOR.sub.b, —(CHR.sub.d).sub.rS(O).sub.pR.sub.c, —(CHR.sub.d).sub.rS(O).sub.pNR.sub.aR.sub.a, —(CHR.sub.d).sub.rNR.sub.aS(O).sub.pR.sub.c, —(CHR.sub.d).sub.rNR.sub.aR.sub.a, —(CHR.sub.d).sub.rNR.sub.aC(═O)R.sub.b, —(CHR.sub.d).sub.rNR.sub.aC(═O)OR.sub.b, —(CHR.sub.d).sub.rNR.sub.aC(═O)NR.sub.aR.sub.a, —(CHR.sub.d).sub.rC(═O)R.sub.b, —(CHR.sub.d).sub.rC(═O)OR.sub.b, —(CHR.sub.d).sub.rC(═O)NR.sub.aR.sub.a, —(CHR.sub.d).sub.rOC(═O)R.sub.b, —(CHR.sub.d).sub.rOC(═O)OR.sub.b, —(CHR.sub.d).sub.rO(CH.sub.2).sub.rC(═O)NR.sub.aR.sub.a, C.sub.3-6cycloalkyl substituted with 0-4 R.sub.e, aryl substituted with 0-4 R.sub.e, and heterocyclyl substituted with 0-4 R.sub.e; R.sub.6 is selected from H, C.sub.1-3alkyl substituted with 0-4 R.sub.e, —S(O).sub.pR.sub.c, —(CH.sub.2)C(═O)R.sub.b, —(CH.sub.2).sub.rC(═O)OR.sub.b, —(CH.sub.2).sub.rC(═O)(CH.sub.2).sub.rNR.sub.aR.sub.a, —C(═O)(CH.sub.2).sub.rNR.sub.aC(═O)R.sub.b, —S(O).sub.pNR.sub.aR.sub.a, —(CH.sub.2).sub.r—C.sub.3-6cycloalkyl substituted with 0-4 R.sub.e, —(CH.sub.2).sub.r-aryl substituted with 0-4 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-4 R.sub.e; R.sub.7 is selected from H, F, Cl, CN, C.sub.1-3 alkyl, ═N—OR.sub.b, —(CH.sub.2)OR.sub.b, —(CH.sub.2).sub.rNR.sub.aR.sub.a, —NR.sub.aC(═NH)C.sub.1-3alkyl, —NR.sub.aC(═O)OR.sub.b, carbocyclyl, and heterocyclyl; alternatively, two R.sub.7 groups are taken together to form carbocyclyl or heterocyclyl; R.sub.8, at each occurrence, is independently selected from H, F, Cl, Br, and C.sub.1-4alkyl substituted with 0-5 R.sub.e; R.sub.a, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; or R.sub.a and R.sub.a together with the nitrogen atom to which they are both attached form a heterocyclic ring substituted with 0-5 R.sub.e; R.sub.b, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.c, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-6 carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.d, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, and OH, R.sub.e, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.f, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, —(CH.sub.2).sub.r—C.sub.3-6 cycloalkyl, —(CH.sub.2).sub.r-aryl, —(CH.sub.2).sub.r-heterocyclyl, Si(C.sub.1-4alkyl).sub.3, F, Cl, Br, CN, NO.sub.2, ═O, CO.sub.2H, —(CH.sub.2).sub.rOR.sub.f, S(O).sub.pR.sub.f, C(═O)NR.sub.fR.sub.f, S(O).sub.pNR.sub.fR.sub.f, and —(CH.sub.2).sub.rNR.sub.fR.sub.f; R.sub.f, at each occurrence, is independently selected from H, F, Cl, Br, CN, OH, C.sub.1-5 alkyl optionally substituted with OH, C.sub.2-5 alkenyl, C.sub.2-5 alkynyl, C.sub.3-6 cycloalkyl, and phenyl, or R.sub.f and R.sub.f together with the nitrogen atom to which they are both attached form a heterocyclic ring optionally substituted with C.sub.1-4alkyl; p, at each occurrence, is independently selected from zero, 1, and 2; r, at each occurrence, is independently selected from zero, 1, 2, 3, and 4; provided: (1) when L is absent, R.sub.4 is not ##STR01303## (2) when L is —NR.sub.d—, R.sub.4 is not ##STR01304## and (3) when L is —O—, R.sub.4 is not C.sub.3-6 cycloalkyl.

2. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein: ##STR01305## is selected from ##STR01306## R.sub.1 is selected from CH.sub.3 and CD.sub.3; R.sub.2 is selected from methyl, ethyl and —CH.sub.2-cyclopropyl substituted with 0-3 R.sub.e; R.sub.3 is selected from H, F, Cl, Br, and —OC.sub.1-4 alkyl; L is absent or selected from —NR.sub.d—, —O—, —C(═O)NH—, —S—, and —S(O).sub.2—; R.sub.4 is selected from ##STR01307## ##STR01308## ##STR01309## R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, CN, ═O, C.sub.1-4alkyl substituted with 0-5 R.sub.e, C.sub.2-4alkenyl, C.sub.2-4alkynyl, —(CHR.sub.d).sub.rOR.sub.b, —(CH.sub.2).sub.rS(O).sub.pR.sub.c, —(CH.sub.2).sub.rS(O).sub.pNR.sub.aR.sub.a, —(CH.sub.2).sub.rNR.sub.aS(O).sub.pR.sub.c, —(CH.sub.2).sub.rNR.sub.aR.sub.a, —(CH.sub.2).sub.rNR.sub.aC(═O)R.sub.b, —(CH.sub.2).sub.rNR.sub.aC(═O)OR.sub.b, —(CH.sub.2).sub.rNR.sub.aC(═O)NR.sub.aR.sub.a, —(CH.sub.2).sub.rC(═O)R.sub.b, —(CH.sub.2).sub.rC(═O)OR.sub.b, —(CHR.sub.d).sub.rC(═O)NR.sub.aR.sub.a, —(CH.sub.2).sub.rOC(═O)R.sub.b, —(CH.sub.2).sub.rOC(═O)OR.sub.b, —(CH.sub.2).sub.rO(CH.sub.2).sub.rC(═O)NR.sub.aR.sub.a, C.sub.3-6cycloalkyl substituted with 0-4 R.sub.e, aryl substituted with 0-4 R.sub.e, and heterocyclyl substituted with 0-4 R.sub.e; R.sub.6, at each occurrence, is independently selected from H, C.sub.1-3alkyl substituted with 0-4 R.sub.e, —S(O).sub.pR.sub.c, —C(═O)R.sub.b, —(CH.sub.2).sub.rC(═O)OR.sub.b, —(CH.sub.2).sub.rC(═O)(CH.sub.2).sub.rNR.sub.aR.sub.a, —C(═O)(CH.sub.2).sub.rNR.sub.aC(═O)R.sub.b, —S(O).sub.pNR.sub.aR.sub.a, —(CH.sub.2).sub.r-aryl substituted with 0-4 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-4 R.sub.e; R.sub.a, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; or R.sub.a and R.sub.a together with the nitrogen atom to which they are both attached form a heterocyclic ring substituted with 0-5 R.sub.e; R.sub.b, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.c, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-6 carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.d, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, and OH; R.sub.e, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.f, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, —(CH.sub.2).sub.r—C.sub.3-6 cycloalkyl, —(CH.sub.2).sub.r-aryl, —(CH.sub.2).sub.r-heterocyclyl, F, Cl, Br, CN, NO.sub.2, ═O, —NH.sub.2, —NHC.sub.1-4alkyl, —N(C.sub.1-4alkyl).sub.2, —C(═O)OH, —C(═O)OC.sub.1-4alkyl, —(CH.sub.2).sub.rOH, and —(CH.sub.2).sub.rOC.sub.1-4alkyl; R.sub.f, at each occurrence, is independently selected from H, F, Cl, Br, CN, OH, C.sub.1-5 alkyl optionally substituted with OH, C.sub.3-6 cycloalkyl, and phenyl; p, at each occurrence, is independently selected from zero, 1, and 2; and r, at each occurrence, is independently selected from zero, 1, 2, 3, and 4.

3. The compound according to claim 2 of Formula (II): ##STR01310## or a pharmaceutically acceptable salt thereof, wherein: ##STR01311## is selected from ##STR01312## R.sub.2 is selected from CH.sub.3, CH.sub.2CH.sub.3 and —CH.sub.2-cyclopropyl substituted with 0-2 F, Cl, and CH.sub.3; R.sub.3 is selected from H, F, and —OC.sub.1-4 alkyl; R.sub.4 is selected from ##STR01313## ##STR01314## R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, CN, ═O, C.sub.1-4alkyl substituted with 0-4 R.sub.e, —(CHR.sub.d).sub.rOR.sub.b, —(CH.sub.2).sub.r S(O).sub.pR.sub.c, —S(O).sub.pNR.sub.aR.sub.a, —(CH.sub.2).sub.rNR.sub.aS(O).sub.pR.sub.c, —(CH.sub.2).sub.rNR.sub.aR.sub.a, —(CH.sub.2).sub.rNR.sub.aC(═O)R.sub.b, —NR.sub.aC(═O)OR.sub.b, —NR.sub.aC(═O)NR.sub.aR.sub.a, —(CH.sub.2).sub.rC(═O)R.sub.b, —(CH.sub.2).sub.rC(═O)OR.sub.b, —(CHR.sub.d).sub.rC(═O)NR.sub.aR.sub.a, —(CH.sub.2).sub.rOC(═O)R.sub.b, —(CH.sub.2).sub.rOC(═O)OR.sub.b, —(CH.sub.2).sub.r O(CH.sub.2).sub.rC(═O)NR.sub.aR.sub.a, C.sub.3-6cycloalkyl substituted with 0-4 R.sub.e, aryl substituted with 0-4 R.sub.e, and heterocyclyl substituted with 0-4 R.sub.e; R.sub.6, at each occurrence, is independently selected from H, C.sub.1-3alkyl substituted with 0-4 R.sub.e, —S(O).sub.pR.sub.c, —C(═O)R.sub.b, —(CH.sub.2).sub.rC(═O)OR.sub.b, —(CH.sub.2).sub.rC(═O)NR.sub.aR.sub.a, —C(═O)(CH.sub.2).sub.rNR.sub.aC(═O)R.sub.b, —S(O).sub.pNR.sub.aR.sub.a, aryl substituted with 0-4 R.sub.e, and heterocyclyl substituted with 0-4 R.sub.e; R.sub.a, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; or R.sub.a and R.sub.a together with the nitrogen atom to which they are both attached form a heterocyclic ring substituted with 0-5 R.sub.e; R.sub.b, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.c, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-6 carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.d, at each occurrence, is independently selected from H and C.sub.1-6 alkyl substituted with 0-5 R.sub.e; R.sub.e, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.f, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, —(CH.sub.2).sub.r—C.sub.3-6 cycloalkyl, —(CH.sub.2).sub.r-aryl, —(CH.sub.2).sub.r-heterocyclyl, F, Cl, Br, CN, NO.sub.2, ═O, —NH.sub.2, —NHC.sub.1-4alkyl, —N(C.sub.1-4alkyl).sub.2, —C(═O)OH, —C(═O)OC.sub.1-4alkyl, —(CH.sub.2).sub.rOH, and —(CH.sub.2).sub.rOC.sub.1-4alkyl; R.sub.f, at each occurrence, is independently selected from H, F, Cl, Br, CN, OH, C.sub.1-5 alkyl optionally substituted with OH, C.sub.3-6 cycloalkyl, and phenyl; p, at each occurrence, is independently selected from zero, 1, and 2; and r, at each occurrence, is independently selected from zero, 1, 2, 3, and 4.

4. The compound according to claim 3 of Formula (III): ##STR01315## or a pharmaceutically acceptable salt thereof, wherein: ##STR01316## is selected from ##STR01317## R.sub.2 is —CH.sub.2-cyclopropyl; R.sub.3 is —OC.sub.1-4 alkyl; R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, CN, C.sub.1-4alkyl substituted with 0-4 R.sub.e, —(CHR.sub.d).sub.rOR.sub.b, —(CH.sub.2).sub.rS(O).sub.pR.sub.c, —S(O).sub.pNR.sub.aR.sub.a, —(CH.sub.2).sub.rNHS(O).sub.pR.sub.c, —(CH.sub.2).sub.rNR.sub.aR.sub.a, —(CH.sub.2).sub.rNHC(═O)R.sub.b, —NHC(═O)OR.sub.b, —(CHR.sub.d).sub.rC(═O)NR.sub.aR.sub.a, —(CH.sub.2).sub.rC(═O)OR.sub.b, —OC(═O)OR.sub.b, —O(CH.sub.2).sub.0-1C(═O)NR.sub.aR.sub.a, C.sub.3-6cycloalkyl substituted with 0-4 R.sub.e, aryl substituted with 0-4 R.sub.e, and heterocyclyl substituted with 0-4 R.sub.e; R.sub.a, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; or R.sub.a and R.sub.a together with the nitrogen atom to which they are both attached form a heterocyclic ring substituted with 0-5 R.sub.e; R.sub.b, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.c, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-6 carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.d, at each occurrence, is independently selected from H, C.sub.1-4 alkyl, and OH; R.sub.e, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.f, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, —(CH.sub.2).sub.r—C.sub.3-6 cycloalkyl, —(CH.sub.2).sub.r-aryl, —(CH.sub.2).sub.r-heterocyclyl, F, Cl, Br, CN, NO.sub.2, ═O, —NH.sub.2, —NHC.sub.1-4alkyl, —N(C.sub.1-4alkyl).sub.2, —C(═O)OH, —C(═O)OC.sub.1-4alkyl, —(CH.sub.2).sub.rOH, —(CH.sub.2).sub.rOC.sub.1-4alkyl, and SO.sub.2C.sub.1-4alkyl; R.sub.f, at each occurrence, is independently selected from H, F, Cl, Br, CN, OH, C.sub.1-5 alkyl optionally substituted with OH, C.sub.3-6 cycloalkyl, and phenyl; p, at each occurrence, is independently selected from zero, 1, and 2; and r, at each occurrence, is independently selected from zero, 1, 2, 3, and 4.

5. The compound according to claim 4, or a pharmaceutically acceptable salt thereof, wherein: R.sub.3 is —OCH.sub.3; R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, CN, C.sub.1-4alkyl, —(CH.sub.2).sub.0-1OR.sub.b, —S(O).sub.2NH.sub.2, —NHS(O).sub.2C.sub.1-3 alkyl, —NHS(O).sub.2C.sub.2-4alkenyl, —NHC(═O)R.sub.b, —C(═O)NH.sub.2 and heterocyclyl selected from ##STR01318## R.sub.b, at each occurrence, is independently selected from H and C.sub.1-6 alkyl substituted with 0-5 R.sub.e, R.sub.e, at each occurrence, is independently selected from C.sub.1-6 alkyl, F, Cl, Br, CN, NO.sub.2, ═O, —NH.sub.2, —NHC.sub.1-4alkyl, —N(C.sub.1-4alkyl).sub.2, —C(═O)OH, —C(═O)OC.sub.1-4alkyl, —(CH.sub.2).sub.rOH, —(CH.sub.2)OC.sub.1-4alkyl, and SO.sub.2C.sub.1-4alkyl; and r, at each occurrence, is independently selected from zero and 1.

6. The compound according to claim 3 or a pharmaceutically acceptable salt thereof, wherein: ##STR01319## is selected from and ##STR01320## R.sub.2 is —CH.sub.2-cyclopropyl; R.sub.3 is —OC.sub.1-4 alkyl; R.sub.4 is selected from ##STR01321## R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, CN, C.sub.1-4alkyl substituted with 0-4 R.sub.e, —(CH.sub.2).sub.rOR.sub.b, —S(O).sub.pR.sub.c, —S(O).sub.pNR.sub.aR.sub.a, —(CH.sub.2).sub.rNR.sub.aS(O).sub.pR.sub.c, —(CH.sub.2).sub.rNR.sub.aR.sub.a, —(CH.sub.2).sub.rNR.sub.aC(═O)R.sub.b, —NR.sub.aC(═O)OR.sub.b, —NR.sub.aC(═O)NR.sub.aR.sub.a, —(CH.sub.2).sub.rC(═O)R.sub.b, —(CH.sub.2).sub.rC(═O)OR.sub.b, —(CH.sub.2).sub.rC(═O)NR.sub.aR.sub.a, —(CH.sub.2OC(═O)R.sub.b, C.sub.3-6cycloalkyl substituted with 0-4 R.sub.e, aryl substituted with 0-4 R.sub.e, and heterocyclyl substituted with 0-4 R.sub.e; R.sub.a, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; or R.sub.a and R.sub.a together with the nitrogen atom to which they are both attached form a heterocyclic ring substituted with 0-5 R.sub.e; R.sub.b, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.c, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-6 carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.e, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.f, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, —(CH.sub.2).sub.r—C.sub.3-6 cycloalkyl, —(CH.sub.2).sub.r-aryl, F, Cl, Br, CN, NO.sub.2, ═O, —NH.sub.2, —NHC.sub.1-4alkyl, —N(C.sub.1-4alkyl).sub.2, —C(═O)OH, —C(═O)OC.sub.1-4alkyl, —(CH.sub.2).sub.rOH, and —(CH.sub.2).sub.rOC.sub.1-4alkyl; R.sub.f, at each occurrence, is independently selected from H, F, Cl, Br, CN, OH, C.sub.1-5 alkyl optionally substituted with OH, C.sub.3-6 cycloalkyl, and phenyl; p, at each occurrence, is independently selected from zero, 1, and 2; and r, at each occurrence, is independently selected from zero, 1, 2, 3, and 4.

7. The compound according to claim 6, or a pharmaceutically acceptable salt thereof, wherein: R.sub.3 is —OCH.sub.3; R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, C.sub.1-4alkyl, —OH, —OC.sub.1-3alkyl, —NHS(O).sub.2C.sub.2-4alkenyl, NHC(═O)OC.sub.1-4 alkyl, C(═O)NH.sub.2, C(═O)NHC.sub.1-4alkyl, and heterocyclyl selected from ##STR01322## and R.sub.e, at each occurrence, is independently selected from C.sub.1-6 alkyl, F, Cl, Br, CN, NO.sub.2, ═O, —NH.sub.2, —NHC.sub.1-4alkyl, —N(C.sub.1-4alkyl).sub.2, —C(═O)OH, —C(═O)OC.sub.1-4alkyl, —(CH.sub.2).sub.rOH, —(CH.sub.2)OC.sub.1-4alkyl, and SO.sub.2C.sub.1-4alkyl.

8. The compound according to claim 3 or a pharmaceutically acceptable salt thereof, wherein: ##STR01323## is selected from ##STR01324## R.sub.2 is —CH.sub.2-cyclopropyl; R.sub.3 is —OC.sub.1-4 alkyl; R.sub.4 is selected from ##STR01325## ##STR01326## R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, CN C.sub.1-4alkyl, —OR.sub.b, —S(O).sub.pR.sub.c—(CH.sub.2).sub.rNR.sub.aS(O).sub.pR.sub.c, —(CH.sub.2).sub.rNR.sub.aR.sub.a, —(CH.sub.2).sub.rNR.sub.aC(═O)R.sub.b, —NR.sub.aC(═O)OR.sub.b, —C(═O)OR.sub.b, C(═O)NR.sub.aR.sub.a, C.sub.3-6cycloalkyl substituted with 0-4 R.sub.e, aryl substituted with 0-4 R.sub.e, and heterocyclyl substituted with 0-4 R.sub.e; R.sub.6, at each occurrence, is independently selected from H, C.sub.1-3alkyl substituted with 0-4 R.sub.e, —S(O).sub.pR.sub.c, —C(═O)R.sub.b, —C(═O)OR.sub.b, —(CH.sub.2).sub.r—C(═O)NR.sub.aR.sub.a, —C(═O)CH.sub.2).sub.rNR.sub.aC(═O)R.sub.b, —S(O).sub.pNR.sub.aR.sub.a, aryl substituted with 0-4 R.sub.e, and heterocyclyl substituted with 0-4 R.sub.e; R.sub.a, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; or R.sub.a and R.sub.a together with the nitrogen atom to which they are both attached form a heterocyclic ring substituted with 0-5 R.sub.e; R.sub.b, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.c, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-6 carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.e, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.f, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, —(CH.sub.2).sub.r—C.sub.3-6 cycloalkyl, —(CH.sub.2).sub.r-aryl, F, Cl, Br, CN, NO.sub.2, ═O, —NH.sub.2, —NHC.sub.1-4alkyl, —N(C.sub.1-4alkyl).sub.2, —C(═O)OH, —C(═O)OC.sub.1-4alkyl, —(CH.sub.2).sub.rOH, and —(CH.sub.2).sub.rOC.sub.1-4alkyl; R.sub.f, at each occurrence, is independently selected from H, F, Cl, Br, CN, OH, C.sub.1-5 alkyl optionally substituted with OH, C.sub.3-6 cycloalkyl, and phenyl; p, at each occurrence, is independently selected from zero, 1, and 2; and r, at each occurrence, is independently selected from zero, 1, 2, 3, and 4.

9. The compound according to claim 8, or a pharmaceutically acceptable salt thereof, wherein: R.sub.4 is selected from ##STR01327## R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, C.sub.1-4alkyl, OH, and —C(═O)OH.

10. The compound according to claim 2 of Formula (IV): ##STR01328## or a pharmaceutically acceptable salt thereof, wherein: ##STR01329## is selected from ##STR01330## R.sub.2 is selected from CH.sub.3 and —CH.sub.2-cyclopropyl; R.sub.3 is selected from H, F, and —OC.sub.1-4 alkyl; R.sub.4 is selected from ##STR01331## R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, CN, C.sub.1-4alkyl, —(CH.sub.2).sub.rOR.sub.b, —NR.sub.aS(O).sub.pR.sub.c, —NR.sub.aR.sub.a, —NR.sub.aC(═O)R.sub.b, —NR.sub.aC(═O)OR.sub.b, —C(═O)OR.sub.b, —C(═O)NR.sub.aR.sub.a, —NR.sub.aC(═O)NR.sub.aR.sub.a, C.sub.3-6cycloalkyl substituted with 0-4 R.sub.e, aryl substituted with 0-4 R.sub.e, and heterocyclyl substituted with 0-4 R.sub.e; R.sub.6, at each occurrence, is independently selected from H and C.sub.1-3alkyl; R.sub.a, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.b, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.c, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-6 carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.d, at each occurrence, is independently selected from H and C.sub.1-3 alkyl; R.sub.e, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.f, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, —(CH.sub.2).sub.r—C.sub.3-6 cycloalkyl, —(CH.sub.2).sub.r-aryl, F, Cl, Br, CN, NO.sub.2, ═O, N(C.sub.1-4alkyl).sub.2, —C(═O)OH, —C(═O)OC.sub.1-4alkyl, —(CH.sub.2).sub.rOH, and —(CH.sub.2)OC.sub.1-4alkyl; R.sub.f, at each occurrence, is independently selected from H, F, Cl, Br, CN, OH, C.sub.1-5 alkyl optionally substituted with OH, C.sub.3-6 cycloalkyl, and phenyl; p, at each occurrence, is independently selected from zero, 1, and 2; and r, at each occurrence, is independently selected from zero, 1, 2, 3, and 4.

11. The compound according to claim 10, or a pharmaceutically acceptable salt thereof, wherein: R.sub.2 is CH.sub.2-cyclopropyl; R.sub.3 is —OCH.sub.3; R.sub.4 is ##STR01332## R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, C.sub.1-4alkyl, and —(CH.sub.2).sub.0-1OH; and R.sub.d is H.

12. The compound according to claim 2 or a pharmaceutically acceptable salt thereof, wherein: L is —C(═O)NH—; R.sub.2 is —CH.sub.2-cyclopropyl; R.sub.3 is —OC.sub.1-4 alkyl; R.sub.4 is selected from ##STR01333## R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, C.sub.1-4alkyl, —OH, and —CN; and R.sub.6, at each occurrence, is independently selected from H and C.sub.1-3alkyl.

13. The compound according to claim 2 or a pharmaceutically acceptable salt thereof, wherein: L is —O—; R.sub.2 is —CH.sub.2-cyclopropyl; R.sub.3 is —OC.sub.1-4alkyl; R.sub.4 is selected from ##STR01334## and R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, C.sub.1-4alkyl, —OH, and —CN.

14. The compound according to claim 2 of Formula (VI): ##STR01335## or a pharmaceutically acceptable salt thereof, wherein: ##STR01336## is selected from ##STR01337## R.sub.2 is —CH.sub.2-cyclopropyl; R.sub.4 is selected from ##STR01338## and R.sub.5 is selected from H, OH, CH.sub.2OH, and —C(CH.sub.3).sub.2OH.

15. The compound according to claim 2 of Formula (VII): ##STR01339## or a pharmaceutically acceptable salt thereof, wherein: ##STR01340## is selected from ##STR01341## R.sub.2 is —CH.sub.2-cyclopropyl; R.sub.4 is selected from ##STR01342## R.sub.5, at each occurrence, is independently selected from F, Cl, C.sub.1-4alkyl, —(CH.sub.2OR.sub.b, —S(O).sub.2NR.sub.aR.sub.a, —NR.sub.aS(O).sub.2R.sub.c, and —C(═O)NR.sub.aR.sub.a; R.sub.6, at each occurrence, is independently selected from H and C.sub.1-3alkyl; R.sub.a, at each occurrence, is independently selected from H and C.sub.1-4 alkyl substituted with 0-5 R.sub.e; R.sub.b, at each occurrence, is independently selected from H and C.sub.1-4 alkyl substituted with 0-5 R.sub.e, R.sub.c, at each occurrence, is independently C.sub.1-4 alkyl substituted with 0-5 R.sub.e; R.sub.e, at each occurrence, is independently selected from F, Cl, Br, —OH, and —OC.sub.1-4alkyl; r, at each occurrence, is independently selected from zero, 1, and 2.

16. A pharmaceutical composition comprising the compound according to claim 1 and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

17. The composition according to claim 16, in combination with an additional therapeutic agent.

18. A method of inhibiting PAD4 in a subject or in a biological sample comprising the step of contacting the PAD4 with a compound according to claim 1.

Description

DETAILED DESCRIPTION OF THE INVENTION

1. General Description of Certain Aspects of the Invention

(1) In some embodiments, such compounds include those of the formulae described herein, or a pharmaceutically acceptable salt thereof, wherein each variable is as defined herein and described in embodiments. Such compounds have the structure of Formula (I):

(2) ##STR00003##
or a pharmaceutically acceptable salt thereof, wherein: Q is selected from N and CH; Ring A is 4- to 15-membered heterocyclyl substituted with 1-4 R.sub.7; R.sub.1 is selected from CH.sub.3 and CD.sub.3; R.sub.2 is selected from H, C.sub.1-3 alkyl substituted with 0-2 C.sub.3-6 cycloalkyl substituted with 0-4 F, Cl, and C.sub.1-3 alkyl; R.sub.3 is selected from H, F, Cl, Br, —OR.sub.b, and C.sub.1-3 alkyl substituted with 0-5 R.sub.e; L is absent or selected from —NR.sub.d—, —O—, —C(═O)NR.sub.d—, and —S(O).sub.p—; R.sub.4 is selected from C.sub.1-6 alkyl substituted with 1-4 F, OH, and C.sub.3-6 cycloalkyl, —(CH.sub.2).sub.r-aryl substituted with 1-7 R.sub.5, —(CH.sub.2).sub.r—C.sub.3-12 cycloalkyl substituted with 1-7 R.sub.5, —(CH.sub.2).sub.r-heterocyclyl comprising carbon atoms and 1-3 heteroatoms selected from N, NR.sub.6, O, and S and substituted with 1-7 R.sub.5; R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, CN, ═O, nitro, C.sub.1-4alkyl substituted with 0-5 R.sub.e, C.sub.2-4alkenyl substituted with 0-5 R.sub.e, C.sub.2-4alkynyl substituted with 0-5 R.sub.e, —(CHR.sub.d).sub.rOR.sub.b, —(CHR.sub.d).sub.rS(O).sub.pR.sub.c, —(CHR.sub.d).sub.rS(O).sub.PNR.sub.aR.sub.a, —(CHR.sub.d).sub.rNR.sub.aS(O).sub.pR.sub.c, —(CHR.sub.d).sub.rNR.sub.aR.sub.a, —(CHR.sub.d).sub.rNR.sub.aC(═O)R.sub.b, —(CHR.sub.d).sub.rNR.sub.aC(═O)OR.sub.b, —(CHR.sub.d).sub.rC(═O)NR.sub.aR.sub.a, —(CHR.sub.d).sub.rC(═O)R.sub.b, —(CHR.sub.d).sub.rC(═O)OR.sub.b, —(CHR.sub.d).sub.rC(═O)NR.sub.aR.sub.a, —(CHR.sub.d).sub.rOC(═O)R.sub.b, —(CHR.sub.d).sub.rOC(═O)OR.sub.b, —(CHR.sub.d).sub.rO(CH.sub.2).sub.rC(═O)NR.sub.aR.sub.a, C.sub.3-6cycloalkyl substituted with 0-4 R.sub.e, aryl substituted with 0-4 R.sub.e, and heterocyclyl substituted with 0-4 R.sub.e; R.sub.6 is selected from H, C.sub.1-3alkyl substituted with 0-4 R.sub.e, —S(O).sub.pR.sub.c, —(CH.sub.2).sub.rC(═O)R.sub.b, —(CH.sub.2).sub.r C(═O)OR.sub.b, —(CH.sub.2).sub.rC(═O)(CH.sub.2).sub.rNR.sub.aR.sub.a, —C(═O)(CH.sub.2).sub.rNR.sub.aC(═O)R.sub.b, —S(O).sub.pNR.sub.aR.sub.a, —(CH.sub.2).sub.r—C.sub.3-6cycloalkyl substituted with 0-4 R.sub.e, —(CH.sub.2).sub.r-aryl substituted with 0-4 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-4 R.sub.e; R.sub.7 is selected from H, F, Cl, CN, C.sub.1-3 alkyl, ═N—OR.sub.b, —(CH.sub.2).sub.rOR.sub.b, —(CH.sub.2).sub.rNR.sub.aR.sub.a, —NR.sub.aC(═NH)C.sub.1-3alkyl, —NR.sub.aC(═O)OR.sub.b, carbocyclyle, and heterocyclyle; alternatively, two R.sub.7 groups are taken together to form carbocyclyl or heterocyclyl; R.sub.8, at each occurrence, is independently selected from H, F, Cl, Br, and C.sub.1-4alkyl substituted with 0-5 R.sub.e; R.sub.a, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; or R.sub.a and R.sub.a together with the nitrogen atom to which they are both attached form a heterocyclic ring substituted with 0-5 R.sub.e; R.sub.b, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6, alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.c, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-6 carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.d, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, and OH, R.sub.e, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.f, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, —(CH.sub.2).sub.rC.sub.3-6 cycloalkyl, —(CH.sub.2).sub.r-aryl, —(CH.sub.2).sub.r-heterocyclyl, Si(C.sub.1-4alkyl).sub.3, F, Cl, Br, CN, NO.sub.2, ═O, CO.sub.2H, —(CH.sub.2).sub.rOR.sub.f, S(O).sub.pR.sub.f, C(═O)NR.sub.fR.sub.f, S(O).sub.pNR.sub.fR.sub.f, and —(CH.sub.2).sub.rNR.sub.fR.sub.f; R.sub.f, at each occurrence, is independently selected from H, F, Cl, Br, CN, OH, C.sub.1-5 alkyl optionally substituted with OH, C.sub.2-5 alkenyl, C.sub.2-5 alkynyl, C.sub.3-6 cycloalkyl, and phenyl, or R.sub.f and R.sub.f together with the nitrogen atom to which they are both attached form a heterocyclic ring optionally substituted with C.sub.1-4alkyl; p, at each occurrence, is independently selected from zero, 1, and 2; r, at each occurrence, is independently selected from zero, 1, 2, 3, and 4; provided: (1) when L is absent, R.sub.4 is not

(3) ##STR00004## (2) when L is —NR.sub.d—, R.sub.4 is not

(4) ##STR00005##
and (3) when L is —O—, R.sub.4 is not C.sub.3-6 cycloalkyl.

2. Definitions

(5) Throughout the specification and the appended claims, a given chemical formula or name shall encompass all stereo and optical isomers and racemates thereof where such isomers exist. Unless otherwise indicated, all chiral (enantiomeric and diastereomeric) and racemic forms are within the scope of the invention. Many geometric isomers of C═C double bonds, C═N double bonds, ring systems, and the like can also be present in the compounds, and all such stable isomers are contemplated in the present invention. Cis- and trans- (or E- and Z-) geometric isomers of the compounds of the present invention are described and may be isolated as a mixture of isomers or as separated isomeric forms. The present compounds can be isolated in optically active or racemic forms. Optically active forms may be prepared by resolution of racemic forms or by synthesis from optically active starting materials. All processes used to prepare compounds of the present invention and intermediates made therein are considered to be part of the present invention. When enantiomeric or diastereomeric products are prepared, they may be separated by conventional methods, for example, by chromatography or fractional crystallization. Depending on the process conditions the end products of the present invention are obtained either in free (neutral) or salt form. Both the free form and the salts of these end products are within the scope of the invention. If so desired, one form of a compound may be converted into another form. A free base or acid may be converted into a salt; a salt may be converted into the free compound or another salt; a mixture of isomeric compounds of the present invention may be separated into the individual isomers. Compounds of the present invention, free form and salts thereof, may exist in multiple tautomeric forms, in which hydrogen atoms are transposed to other parts of the molecules and the chemical bonds between the atoms of the molecules are consequently rearranged. It should be understood that all tautomeric forms, insofar as they may exist, are included within the invention.

(6) As used herein, the term “alkyl” or “alkylene” is intended to include both branched and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms. For examples, “C.sub.1 to C.sub.12 alkyl” or “C.sub.1-12 alkyl” (or alkylene), is intended to include C.sub.1, C.sub.2, C.sub.3, C.sub.4, C.sub.5, C.sub.6, C.sub.7, C.sub.8, C.sub.9, C.sub.10, C.sub.11 and C.sub.12 alkyl groups; “C.sub.4 to C18 alkyl” or “C.sub.4-18 alkyl” (or alkylene), is intended to include C.sub.4, C.sub.5, C.sub.6, C.sub.7, C.sub.8, C.sub.9, C.sub.10, C.sub.11, C.sub.12, C.sub.13, C.sub.14, C.sub.15, C.sub.16, C.sub.17, and C18 alkyl groups. Additionally, for example, “C.sub.1 to C.sub.6 alkyl” or “C.sub.1-6 alkyl” denotes alkyl having 1 to 6 carbon atoms. Alkyl group can be unsubstituted or substituted with at least one hydrogen being replaced by another chemical group. Example alkyl groups include, but are not limited to, methyl (Me), ethyl (Et), propyl (e.g., n-propyl and isopropyl), butyl (e.g., n-butyl, isobutyl, t-butyl), and pentyl (e.g., n-pentyl, isopentyl, neopentyl). When “C.sub.0 alkyl” or “C.sub.0 alkylene” is used, it is intended to denote a direct bond.

(7) “Alkenyl” or “alkenylene” is intended to include hydrocarbon chains of either straight or branched configuration having the specified number of carbon atoms and one or more, preferably one to two, carbon-carbon double bonds that may occur in any stable point along the chain. For example, “C.sub.2 to C.sub.6 alkenyl” or “C.sub.2-6 alkenyl” (or alkenylene), is intended to include C.sub.2, C.sub.3, C.sub.4, C.sub.5, and C.sub.6 alkenyl groups. Examples of alkenyl include, but are not limited to, ethenyl, 1-propenyl, 2-propenyl, 2-butenyl, 3-butenyl, 2-pentenyl, 3, pentenyl, 4-pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-methyl-2-propenyl, and 4-methyl-3-pentenyl.

(8) “Alkynyl” or “alkynylene” is intended to include hydrocarbon chains of either straight or branched configuration having one or more, preferably one to three, carbon-carbon triple bonds that may occur in any stable point along the chain. For example, “C.sub.2 to C.sub.6 alkynyl” or “C.sub.2-6 alkynyl” (or alkynylene), is intended to include C.sub.2, C.sub.3, C.sub.4, C.sub.5, and C.sub.6 alkynyl groups; such as ethynyl, propynyl, butynyl, pentynyl, and hexynyl.

(9) The term “alkoxy” or “alkyloxy” refers to an —O-alkyl group. For example, “C.sub.1 to C.sub.6 alkoxy” or “C.sub.1-6 alkoxy” (or alkyloxy), is intended to include C.sub.1, C.sub.2, C.sub.3, C.sub.4, C.sub.5, and C.sub.6 alkoxy groups. Example alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy (e.g., n-propoxy and isopropoxy), and t-butoxy. Similarly, “alkylthio” or “thioalkoxy” represents an alkyl group as defined above with the indicated number of carbon atoms attached through a sulphur bridge; for example methyl-S— and ethyl-S—.

(10) “Halo” or “halogen” includes fluoro, chloro, bromo, and iodo. “Haloalkyl” is intended to include both branched and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms, substituted with 1 or more halogens. Examples of haloalkyl include, but are not limited to, fluoromethyl, difluoromethyl, trifluoromethyl, trichloromethyl, pentafluoroethyl, pentachloroethyl, 2,2,2-trifluoroethyl, heptafluoropropyl, and heptachloropropyl. Examples of haloalkyl also include “fluoroalkyl” that is intended to include both branched and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms, substituted with 1 or more fluorine atoms.

(11) The term “cycloalkyl” refers to cyclized alkyl groups, including mono-, bi- or poly-cyclic ring systems. For example, “C.sub.3 to C.sub.6 cycloalkyl” or “C.sub.3-6 cycloalkyl” is intended to include C.sub.3, C.sub.4, C.sub.5, and C.sub.6 cycloalkyl groups. Example cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and norbornyl. Branched cycloalkyl groups such as 1-methylcyclopropyl and 2-methylcyclopropyl are included in the definition of “cycloalkyl”. The term “cycloalkenyl” refers to cyclized alkenyl groups. C.sub.4-6 cycloalkenyl is intended to include C.sub.4, C.sub.5, and C.sub.6 cycloalkenyl groups. Example cycloalkenyl groups include, but are not limited to, cyclobutenyl, cyclopentenyl, and cyclohexenyl.

(12) As used herein, “carbocycle”, “carbocyclyl”, or “carbocyclic residue” is intended to mean any stable 3-, 4-, 5-, 6-, 7-, or 8-membered monocyclic or bicyclic or 7-, 8-, 9-, 10-, 11-, 12-, or 13-membered bicyclic or tricyclic hydrocarbon ring, any of which may be saturated, partially unsaturated, unsaturated or aromatic. Examples of such carbocycles include, but are not limited to, cyclopropyl, cyclobutyl, cyclobutenyl, cyclopentyl, cyclopentenyl, cyclohexyl, cycloheptenyl, cycloheptyl, cycloheptenyl, adamantyl, cyclooctyl, cyclooctenyl, cyclooctadienyl, [3.3.0]bicyclooctane, [4.3.0]bicyclononane, [4.4.0]bicyclodecane (decalin), [2.2.2]bicyclooctane, fluorenyl, phenyl, naphthyl, indanyl, adamantyl, anthracenyl, and tetrahydronaphthyl (tetralin). As shown above, bridged rings are also included in the definition of carbocycle (e.g., [2.2.2]bicyclooctane). Preferred carbocycles, unless otherwise specified, are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, indanyl, and tetrahydronaphthyl. When the term “carbocycle” is used, it is intended to include “aryl.” A bridged ring occurs when one or more, preferably one to three, carbon atoms link two non-adjacent carbon atoms. Preferred bridges are one or two carbon atoms. It is noted that a bridge always converts a monocyclic ring into a tricyclic ring. When a ring is bridged, the substituents recited for the ring may also be present on the bridge.

(13) As used herein, the term “bicyclic carbocycle” or “bicyclic carbocyclic group” is intended to mean a stable 9- or 10-membered carbocyclic ring system that contains two fused rings and consists of carbon atoms. Of the two fused rings, one ring is a benzo ring fused to a second ring; and the second ring is a 5- or 6-membered carbon ring which is saturated, partially unsaturated, or unsaturated. The bicyclic carbocyclic group may be attached to its pendant group at any carbon atom which results in a stable structure. The bicyclic carbocyclic group described herein may be substituted on any carbon if the resulting compound is stable. Examples of a bicyclic carbocyclic group are, but not limited to, naphthyl, 1,2-dihydronaphthyl, 1,2,3,4-tetrahydronaphthyl, and indanyl.

(14) “Aryl” groups refer to monocyclic or bicyclic aromatic hydrocarbons, including, for example, phenyl, and naphthyl. Aryl moieties are well known and described, for example, in Lewis, R. J., ed., Hawley's Condensed Chemical Dictionary, 15th Edition, John Wiley & Sons, Inc., New York (2007). “C.sub.6-10 aryl” refers to phenyl and naphthyl.

(15) As used herein, the term “heterocycle”, “heterocyclyl”, or “heterocyclic group” is intended to mean a stable 3-, 4-, 5-, 6-, or 7-membered monocyclic or bicyclic or 7-, 8-, 9-, 10-, 11-, 12-, 13-, or 14-membered polycyclic heterocyclic ring that is saturated, partially unsaturated, or fully unsaturated, and that contains carbon atoms and 1, 2, 3 or 4 heteroatoms independently selected from the group consisting of N, O and S; and including any polycyclic group in which any of the above-defined heterocyclic rings is fused to a benzene ring. The nitrogen and sulfur heteroatoms may optionally be oxidized (i.e., N.fwdarw.O and S(O).sub.p, wherein p is 0, 1 or 2). The nitrogen atom may be substituted or unsubstituted (i.e., N or NR wherein R is H or another substituent, if defined). The heterocyclic ring may be attached to its pendant group at any heteroatom or carbon atom that results in a stable structure. The heterocyclic rings described herein may be substituted on carbon or on a nitrogen atom if the resulting compound is stable. A nitrogen in the heterocycle may optionally be quaternized. It is preferred that when the total number of S and O atoms in the heterocycle exceeds 1, then these heteroatoms are not adjacent to one another. It is preferred that the total number of S and O atoms in the heterocycle is not more than 1. When the term “heterocycle” is used, it is intended to include heteroaryl.

(16) Examples of heterocycles include, but are not limited to, acridinyl, azetidinyl, azocinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzoxazolinyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazolinyl, carbazolyl, 4aH-carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, 2H,6H-1,5,2-dithiazinyl, dihydrofuro[2,3-b]tetrahydrofuran, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, imidazolopyridinyl, indolenyl, indolinyl, indolizinyl, indolyl, 3H-indolyl, isatinoyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl, isothiazolopyridinyl, isoxazolyl, isoxazolopyridinyl, methylenedioxyphenyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinyl, oxazolyl, oxazolopyridinyl, oxazolidinylperimidinyl, oxindolyl, pyrimidinyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, piperidonyl, 4-piperidonyl, piperonyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolopyridinyl, pyrazolyl, pyridazinyl, pyridooxazolyl, pyridoimidazolyl, pyridothiazolyl, pyridinyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, 2-pyrrolidonyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, tetrazolyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, thiazolyl, thienyl, thiazolopyridinyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thiophenyl, triazinyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, and xanthenyl. Also included are fused ring and spiro compounds containing, for example, the above heterocycles.

(17) Examples of 5- to 10-membered heterocycles include, but are not limited to, pyridinyl, furanyl, thienyl, pyrrolyl, pyrazolyl, pyrazinyl, piperazinyl, piperidinyl, imidazolyl, imidazolidinyl, indolyl, tetrazolyl, isoxazolyl, morpholinyl, oxazolyl, oxadiazolyl, oxazolidinyl, tetrahydrofuranyl, thiadiazinyl, thiadiazolyl, thiazolyl, triazinyl, triazolyl, benzimidazolyl, 1H-indazolyl, benzofuranyl, benzothiofuranyl, benztetrazolyl, benzotriazolyl, benzisoxazolyl, benzoxazolyl, oxindolyl, benzoxazolinyl, benzthiazolyl, benzisothiazolyl, isatinoyl, isoquinolinyl, octahydroisoquinolinyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, isoxazolopyridinyl, quinazolinyl, quinolinyl, isothiazolopyridinyl, thiazolopyridinyl, oxazolopyridinyl, imidazolopyridinyl, and pyrazolopyridinyl. Also included are fused ring and spiro compounds containing, for example, the above heterocycles.

(18) Bridged rings are also included in the definition of heterocycle. A bridged ring occurs when one or more, preferably one to three, atoms (i.e., C, O, N, or S) link two non-adjacent carbon or nitrogen atoms. Examples of bridged rings include, but are not limited to, one carbon atom, two carbon atoms, one nitrogen atom, two nitrogen atoms, and a carbon-nitrogen group. It is noted that a bridge always converts a monocyclic ring into a tricyclic ring. When a ring is bridged, the substituents recited for the ring may also be present on the bridge.

(19) As used herein, the term “bicyclic heterocycle” or “bicyclic heterocyclic group” is intended to mean a stable 9- or 10-membered heterocyclic ring system which contains two fused rings and consists of carbon atoms and 1, 2, 3, or 4 heteroatoms independently selected from the group consisting of N, O and S. Of the two fused rings, one ring is a 5- or 6-membered monocyclic aromatic ring comprising a 5-membered heteroaryl ring, a 6-membered heteroaryl ring or a benzo ring, each fused to a second ring. The second ring is a 5- or 6-membered monocyclic ring which is saturated, partially unsaturated, or unsaturated, and comprises a 5-membered heterocycle, a 6-membered heterocycle or a carbocycle (provided the first ring is not benzo when the second ring is a carbocycle).

(20) The bicyclic heterocyclic group may be attached to its pendant group at any heteroatom or carbon atom which results in a stable structure. The bicyclic heterocyclic group described herein may be substituted on carbon or on a nitrogen atom if the resulting compound is stable. It is preferred that when the total number of S and O atoms in the heterocycle exceeds 1, then these heteroatoms are not adjacent to one another. It is preferred that the total number of S and O atoms in the heterocycle is not more than 1.

(21) Examples of a bicyclic heterocyclic group are, but not limited to, quinolinyl, isoquinolinyl, phthalazinyl, quinazolinyl, indolyl, isoindolyl, indolinyl, 1H-indazolyl, benzimidazolyl, 1,2,3,4-tetrahydroquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl, 5,6,7,8-tetrahydro-quinolinyl, 2,3-dihydro-benzofuranyl, chromanyl, 1,2,3,4-tetrahydro-quinoxalinyl, and 1,2,3,4-tetrahydro-quinazolinyl.

(22) As used herein, the term “aromatic heterocyclic group” or “heteroaryl” is intended to mean stable monocyclic and polycyclic aromatic hydrocarbons that include at least one heteroatom ring member such as sulfur, oxygen, or nitrogen. Heteroaryl groups include, without limitation, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, furyl, quinolyl, isoquinolyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrroyl, oxazolyl, benzofuryl, benzothienyl, benzthiazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl, 1,2,4-thiadiazolyl, isothiazolyl, purinyl, carbazolyl, benzimidazolyl, indolinyl, benzodioxolanyl, and benzodioxane. Heteroaryl groups are substituted or unsubstituted. The nitrogen atom is substituted or unsubstituted (i.e., N or NR wherein R is H or another substituent, if defined). The nitrogen and sulfur heteroatoms may optionally be oxidized (i.e., N.fwdarw.O and S(O).sub.p, wherein p is 0, 1 or 2).

(23) Examples of 5- to 6-membered heteroaryls include, but are not limited to, pyridinyl, furanyl, thienyl, pyrrolyl, pyrazolyl, pyrazinyl, imidazolyl, imidazolidinyl, tetrazolyl, isoxazolyl, oxazolyl, oxadiazolyl, oxazolidinyl, thiadiazinyl, thiadiazolyl, thiazolyl, triazinyl, and triazolyl.

(24) The term “counter ion” is used to represent a negatively charged species such as chloride, bromide, hydroxide, acetate, and sulfate or a positively charged species such as sodium (Na.sup.+), potassium (K.sup.+), ammonium (R.sub.nNH.sub.m+ where n=0-4 and m=0-4) and the like.

(25) When a dotted ring is used within a ring structure, this indicates that the ring structure may be saturated, partially saturated or unsaturated.

(26) As used herein, the term “amine protecting group” means any group known in the art of organic synthesis for the protection of amine groups which is stable to an ester reducing agent, a disubstituted hydrazine, R4-M and R7-M, a nucleophile, a hydrazine reducing agent, an activator, a strong base, a hindered amine base and a cyclizing agent. Such amine protecting groups fitting these criteria include those listed in Wuts, P. G. M. et al., Protecting Groups in Organic Synthesis, 4th Edition, Wiley (2007) and The Peptides: Analysis, Synthesis, Biology, Vol. 3, Academic Press, New York (1981), the disclosure of which is hereby incorporated by reference. Examples of amine protecting groups include, but are not limited to, the following: (1) acyl types such as formyl, trifluoroacetyl, phthalyl, and p-toluenesulfonyl; (2) aromatic carbamate types such as benzyloxycarbonyl (Cbz) and substituted benzyloxycarbonyls, 1-(p-biphenyl)-1-methylethoxycarbonyl, and 9-fluorenylmethyloxycarbonyl (Fmoc); (3) aliphatic carbamate types such as tert-butyloxycarbonyl (Boc), ethoxycarbonyl, diisopropylmethoxycarbonyl, and allyloxycarbonyl; (4) cyclic alkyl carbamate types such as cyclopentyloxycarbonyl and adamantyloxycarbonyl; (5) alkyl types such as triphenylmethyl and benzyl; (6) trialkylsilane such as trimethylsilane; (7) thiol containing types such as phenylthiocarbonyl and dithiasuccinoyl; and (8) alkyl types such as triphenylmethyl, methyl, and benzyl; and substituted alkyl types such as 2,2,2-trichloroethyl, 2-phenylethyl, and t-butyl; and trialkylsilane types such as trimethylsilane.

(27) As referred to herein, the term “substituted” means that at least one hydrogen atom is replaced with a non-hydrogen group, provided that normal valencies are maintained and that the substitution results in a stable compound. Ring double bonds, as used herein, are double bonds that are formed between two adjacent ring atoms (e.g., C═C, C═N, or N═N).

(28) In cases wherein there are nitrogen atoms (e.g., amines) on compounds of the present invention, these may be converted to N-oxides by treatment with an oxidizing agent (e.g., mCPBA and/or hydrogen peroxides) to afford other compounds of this invention. Thus, shown and claimed nitrogen atoms are considered to cover both the shown nitrogen and its N-oxide (N.fwdarw.O) derivative.

(29) When any variable occurs more than one time in any constituent or formula for a compound, its definition at each occurrence is independent of its definition at every other occurrence. Thus, for example, if a group is shown to be substituted with 0-3 R, then said group may optionally be substituted with up to three R groups, and at each occurrence R is selected independently from the definition of R.

(30) When a bond to a substituent is shown to cross a bond connecting two atoms in a ring, then such substituent may be bonded to any atom on the ring. When a substituent is listed without indicating the atom in which such substituent is bonded to the rest of the compound of a given formula, then such substituent may be bonded via any atom in such substituent.

(31) Combinations of substituents and/or variables are permissible only if such combinations result in stable compounds.

(32) The phrase “pharmaceutically acceptable” is employed herein to refer to those compounds, materials, compositions, and/or dosage forms that are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, and/or other problem or complication, commensurate with a reasonable benefit/risk ratio.

(33) As used herein, “pharmaceutically acceptable salts” refer to derivatives of the disclosed compounds wherein the parent compound is modified by making acid or base salts thereof. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic groups such as amines; and alkali or organic salts of acidic groups such as carboxylic acids. The pharmaceutically acceptable salts include the conventional non-toxic salts or the quaternary ammonium salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. Examples of pharmaceutically acceptable, nontoxic acid addition salts are salts of an amino group formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid and perchloric acid or with organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid or malonic acid or by using other methods used in the art such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate salts, and the like.

(34) Salts derived from appropriate bases include alkali metal, alkaline earth metal, ammonium and N.sup.+(C.sub.1-4alkyl).sub.4 salts. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Further pharmaceutically acceptable salts include, when appropriate, nontoxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, loweralkyl sulfonate and aryl sulfonate.

(35) The pharmaceutically acceptable salts of the present invention can be synthesized from the parent compound that contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two; generally, nonaqueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. Lists of suitable salts are found in Allen, Jr., L. V., ed., Remington: The Science and Practice of Pharmacy, 22nd Edition, Pharmaceutical Press, London, UK (2012), the disclosure of which is hereby incorporated by reference.

(36) In addition, compounds of formula I may have prodrug forms. Any compound that will be converted in vivo to provide the bioactive agent (i.e., a compound of formula I) is a prodrug within the scope and spirit of the invention. Various forms of prodrugs are well known in the art. For examples of such prodrug derivatives, see: a) Bundgaard, H., ed., Design of Prodrugs, Elsevier (1985), and Widder, K. et al., eds., Methods in Enzymology, 112:309-396, Academic Press (1985); b) Bundgaard, H., Chapter 5, “Design and Application of Prodrugs”, Krosgaard-Larsen, P. et al., eds., A Textbook of Drug Design and Development, pp. 113-191, Harwood Academic Publishers (1991); c) Bundgaard, H., Adv. Drug Deliv. Rev., 8:1-38 (1992); d) Bundgaard, H. et al., J. Pharm. Sci., 77:285 (1988); e) Kakeya, N. et al., Chem. Pharm. Bull., 32:692 (1984); and f) Rautio, J., ed., Prodrugs and Targeted Delivery (Methods and Principles in Medicinal Chemistry), Vol. 47, Wiley-VCH (2011).

(37) Compounds containing a carboxy group can form physiologically hydrolyzable esters that serve as prodrugs by being hydrolyzed in the body to yield formula I compounds per se. Such prodrugs are preferably administered orally since hydrolysis in many instances occurs principally under the influence of the digestive enzymes. Parenteral administration may be used where the ester per se is active, or in those instances where hydrolysis occurs in the blood. Examples of physiologically hydrolyzable esters of compounds of formula I include C.sub.1-6alkyl, C.sub.1-6alkylbenzyl, 4-methoxybenzyl, indanyl, phthalyl, methoxymethyl, C.sub.1-6 alkanoyloxy-C.sub.1-6alkyl (e.g., acetoxymethyl, pivaloyloxymethyl or propionyloxymethyl), C.sub.1-6alkoxycarbonyloxy-C.sub.1-6alkyl (e.g., methoxycarbonyl-oxymethyl or ethoxycarbonyloxymethyl, glycyloxymethyl, phenylglycyloxymethyl, (5-methyl-2-oxo-1,3-dioxolen-4-yl)-methyl), and other well known physiologically hydrolyzable esters used, for example, in the penicillin and cephalosporin arts. Such esters may be prepared by conventional techniques known in the art.

(38) Preparation of prodrugs is well known in the art and described in, for example, King, F. D., ed., Medicinal Chemistry: Principles and Practice, The Royal Society of Chemistry, Cambridge, UK (2nd Edition, reproduced (2006)); Testa, B. et al., Hydrolysis in Drug and Prodrug Metabolism. Chemistry, Biochemistry and Ezymology, VCHA and Wiley-VCH, Zurich, Switzerland (2003); Wermuth, C. G., ed., The Practice of Medicinal Chemistry, 3rd Edition, Academic Press, San Diego, Calif. (2008).

(39) The present invention is intended to include all isotopes of atoms occurring in the present compounds. Isotopes include those atoms having the same atomic number but different mass numbers. By way of general example and without limitation, isotopes of hydrogen include deuterium (symbol D or 2H) and tritium (symbol T or 3H). For example, a methyl group may be represented by CH.sub.3 or CD.sub.3. Isotopes of carbon include .sup.13C and .sup.14C. Isotopically-labeled compounds of the invention can generally be prepared by conventional techniques known to those skilled in the art or by processes analogous to those described herein, using an appropriate isotopically-labeled reagent in place of the non-labeled reagent otherwise employed.

(40) The term “solvate” means a physical association of a compound of this invention with one or more solvent molecules, whether organic or inorganic. This physical association includes hydrogen bonding. In certain instances the solvate will be capable of isolation, for example when one or more solvent molecules are incorporated in the crystal lattice of the crystalline solid. The solvent molecules in the solvate may be present in a regular arrangement and/or a non-ordered arrangement. The solvate may comprise either a stoichiometric or nonstoichiometric amount of the solvent molecules. “Solvate” encompasses both solution-phase and isolable solvates. Exemplary solvates include, but are not limited to, hydrates, ethanolates, methanolates, and isopropanolates. Methods of solvation are generally known in the art.

(41) The terms “measurable affinity” and “measurably inhibit,” as used herein, means a measurable change in PAD4 activity between a sample comprising a compound of the present invention, or composition thereof, and PAD4, and an equivalent sample comprising PAD4 in the absence of said compound, or composition thereof.

(42) Abbreviations as used herein, are defined as follows: “1×” for once, “2×” for twice, “3×” for thrice, “° C.” for degrees Celsius, “eq” for equivalent or equivalents, “g” for gram or grams, “mg” for milligram or milligrams, “L” for liter or liters, “mL” for milliliter or milliliters, “μL” for microliter or microliters, “N” for normal, “M” for molar, “mmol” for millimole or millimoles, “min” for minute or min, “h” for hour or h, “rt” for room temperature, “RT” for retention time, “atm” for atmosphere, “psi” for pounds per square inch, “conc.” for concentrate, “aq” for “aqueous”, “sat” or “sat'd” for saturated, “MW” for molecular weight, “mp” for melting point, “MS” or “Mass Spec” for mass spectrometry, “ESI” for electrospray ionization mass spectroscopy, “HR” for high resolution, “HRMS” for high resolution mass spectrometry, “LCMS” for liquid chromatography mass spectrometry, “HPLC” for high pressure liquid chromatography, “RP HPLC” for reverse phase HPLC, “TLC” or “tic” for thin layer chromatography, “NMR” for nuclear magnetic resonance spectroscopy, “nOe” for nuclear Overhauser effect spectroscopy, “.sup.1H” for proton, “δ” for delta, “s” for singlet, “d” for doublet, “t” for triplet, “q” for quartet, “m” for multiplet, “br” for broad, “Hz” for hertz, and “α”, “β”, “R”, “S”, “E”, “Z” and “ee” are stereochemical designations familiar to one skilled in the art. As used herein, the term “pharmaceutically acceptable salt” refers to those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like, and are commensurate with a reasonable benefit/risk ratio. AcOH or HOAc acetic acid ACN acetonitrile Alk Alkyl AlMe.sub.3 Trimethylaluminum BBr.sub.3 boron tribromide Bn benzyl Boc tert-butyloxycarbonyl BOP reagent benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate Bu butyl i-Bu isobutyl t-Bu tert-butyl t-BuOH tert-butanol Cbz carbobenzyloxy CDCl.sub.3 deutero-chloroform CD.sub.3OD deutero-methanol CH.sub.2Cl.sub.2 dichloromethane CH.sub.3CN acetonitrile CHCl.sub.3 chloroform DCM dichloromethane DIEA, DIPEA or Hunig's base diisopropylethylamine DMF dimethyl formamide DMSO dimethyl sulfoxide Et ethyl Et.sub.3N or TEA triethylamine Et.sub.2O diethyl ether EtOAc ethyl acetate EtOH ethanol HCl hydrochloric acid HPLC high-performance liquid chromatography K.sub.2CO.sub.3 potassium carbonate K.sub.2HPO.sub.4 potassium hydrogenphosphate LCMS liquid chromatography mass spectrometry LiHMDS lithium bis(trimethylsilyl)amide LG leaving group Me methyl MeOH methanol MgSO.sub.4 magnesium sulfate MsOH or MSA methylsulfonic acid NaCl sodium chloride Na.sub.2CO.sub.3 sodium carbonate NaHCO.sub.3 sodium bicarbonate NaOH sodium hydroxide Na.sub.2SO.sub.4 sodium sulfate NH.sub.3 ammonia NH.sub.4Cl ammonium chloride NH.sub.4OAc ammonium acetate Pd(OAc).sub.2 palladium(II) acetate Pd(dppf)Cl.sub.2 [1,1′-Bis(diphenylphosphino)ferrocene]palladium(II) dichloride Pd(PPh.sub.3).sub.4 tetrakis(triphenylphosphine)palladium(0) PG protecting group Ph phenyl Pr propyl i-Pr isopropyl i-PrOH or IPA isopropanol Rt retention time SiO.sub.2 silica oxide SFC supercritical fluid chromatography TBAI Tetrabutylammonium iodide TEA triethylamine TFA trifluoroacetic acid TFAA Trifluoroacetic anhydride THF tetrahydrofuran TiCl.sub.4 titanium tetrachloride T3P 1-propanephosphonic acid cyclic anhydride

3. Description of Exemplary Compounds

(43) In a first aspect, the present invention provides a compound of Formula (I):

(44) ##STR00006##
or a pharmaceutically acceptable salt thereof, wherein: Q is selected from N and CH; Ring A is 4- to 15-membered heterocyclyl substituted with 1-4 R.sub.7; R.sub.1 is selected from CH.sub.3 and CD.sub.3; R.sub.2 is selected from H, C.sub.1-3 alkyl substituted with 0-5 R.sub.e, and C.sub.3-6 cycloalkyl substituted with 0-5 R.sub.e; R.sub.3 is selected from H, F, Cl, Br, —OR.sub.b, and C.sub.1-3 alkyl substituted with 0-5 R.sub.e; L is absent or selected from —NR.sub.d—, —O—, —C(═O)NR.sub.d—, and —S(O).sub.p—; R.sub.4 is selected from —(CH.sub.2).sub.r-aryl substituted with 1-5 R.sub.5, —(CH.sub.2).sub.r—C.sub.3-12 cycloalkyl substituted with 1-5 R.sub.5, —(CH.sub.2).sub.r-heterocyclyl comprising carbon atoms and 1-3 heteroatoms selected from N, NR.sub.6, O, and S and substituted with 1-5 R.sub.5; R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, CN, nitro, C.sub.1-4alkyl substituted with 0-5 R.sub.e, C.sub.2-4alkenyl substituted with 0-5 R.sub.e, C.sub.2-4alkynyl substituted with 0-5 R.sub.e, —(CHR.sub.d).sub.rOR.sub.b, —(CHR.sub.d).sub.rS(O).sub.pR.sub.c, —(CHR.sub.d).sub.rS(O).sub.pNR.sub.aR.sub.a, —(CHR.sub.d).sub.rNR.sub.aS(O).sub.pR.sub.c, —(CHR.sub.d).sub.rNR.sub.aR.sub.a, —(CHR.sub.d).sub.rNR.sub.aC(═O)R.sub.b, —(CHR.sub.d).sub.rNR.sub.aC(═O)OR.sub.b, —(CHR.sub.d).sub.rNR.sub.aC(═O)NR.sub.aR.sub.a, —(CHR.sub.d).sub.rC(═O)R.sub.b, —(CHR.sub.d).sub.rC(═O)OR.sub.b, —(CHR.sub.d).sub.rC(═O)NR.sub.aR.sub.a, —(CHR.sub.d).sub.rOC(═O)R.sub.b, C.sub.3-6cycloalkyl substituted with 0-4 R.sub.e, aryl substituted with 0-4 R.sub.e, and heterocyclyl substituted with 0-4 R.sub.e; R.sub.6 is selected from H, C.sub.1-3alkyl substituted with 0-4 R.sub.e, —S(O).sub.pR.sub.c, —C(═O)R.sub.b, —C(═O)OR.sub.b, —C(═O)(CH.sub.2).sub.rNR.sub.aR.sub.a, —S(O).sub.pNR.sub.aR.sub.a, —(CH.sub.2).sub.rC.sub.3-6cycloalkyl substituted with 0-4 R.sub.e, —(CH.sub.2).sub.r-aryl substituted with 0-4 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-4 R.sub.e; R.sub.7 is selected from H, F, Cl, CN, C.sub.1-3 alkyl, ═N—OR.sub.b, —(CH.sub.2).sub.rOR.sub.b, —(CH.sub.2).sub.rNR.sub.aR.sub.a, —NR.sub.aC(═NH)C.sub.1-3alkyl, —NR.sub.aC(═O)OR.sub.b, a carbocyle, and a heterocycle; alternatively, two R.sub.7 groups are taken together to form a carbocycle or heterocyle; R.sub.8, at each occurrence, is independently selected from H, F, Cl, Br, and C.sub.1-4alkyl substituted with 0-5 R.sub.e; R.sub.a, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; or R.sub.a and R.sub.a together with the nitrogen atom to which they are both attached form a heterocyclic ring substituted with 0-5 R.sub.e; R.sub.b, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.c, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-6carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.d, at each occurrence, is independently selected from H and C.sub.1-6 alkyl substituted with 0-5 R.sub.e, R.sub.e, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.f, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, —(CH.sub.2).sub.rC.sub.3-6 cycloalkyl, —(CH.sub.2).sub.r-aryl, Si(C.sub.1-4alkyl).sub.3, F, Cl, Br, CN, NO.sub.2, ═O, CO.sub.2H, —(CH.sub.2).sub.rOR.sub.f, S(O).sub.pR.sub.f, C(═O)NR.sub.fR.sub.f, S(O).sub.pNR.sub.fR.sub.f, and —(CH.sub.2).sub.rNR.sub.fR.sub.f; R.sub.f, at each occurrence, is independently selected from H, F, Cl, Br, CN, OH, C.sub.1-5 alkyl optionally substituted with OH, C.sub.2-5 alkenyl, C.sub.2-5 alkynyl, C.sub.3-6 cycloalkyl, and phenyl, or R.sub.f and R.sub.f together with the nitrogen atom to which they are both attached form a heterocyclic ring optionally substituted with C.sub.1-4alkyl; p, at each occurrence, is independently selected from zero, 1, and 2; r, at each occurrence, is independently selected from zero, 1, 2, 3, and 4; and provided: (1) when L is absent, R.sub.4 is not

(45) ##STR00007## (2) when L is —NR.sub.d—, R.sub.4 is not

(46) ##STR00008##
and (3) when L is —O—, R.sub.4 is not C.sub.3-6 cycloalkyl.

(47) In a second aspect, the present invention provides a compound or a pharmaceutically acceptable salt thereof, within the scope of the first aspect, wherein: Ring A is selected from

(48) ##STR00009## R.sub.1 is selected from CH.sub.3 and CD.sub.3; R.sub.2 is selected from methyl, ethyl, and —CH.sub.2-cyclopropyl substituted with 0-3 R.sub.e; R.sub.3 is selected from H, F, Cl, Br, and —OC.sub.1-4 alkyl; L is absent or selected from —NR.sub.d—, —O—, —C(═O)NH—, —S—, and —S(O).sub.2—; R.sub.4 is selected from

(49) ##STR00010## ##STR00011## ##STR00012## ##STR00013## ##STR00014## R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, CN, C.sub.1-4alkyl substituted with 0-5 R.sub.e, C.sub.2-4alkenyl, C.sub.2-4alkynyl, —(CHR.sub.d).sub.rOR.sub.b, —(CH.sub.2).sub.rS(O).sub.pR.sub.c, —(CH.sub.2).sub.rS(O).sub.pNR.sub.aR.sub.a, —(CH.sub.2).sub.rNR.sub.aS(O).sub.pR.sub.c, —(CH.sub.2)NR.sub.aR.sub.a, —(CH.sub.2).sub.rNR.sub.aC(═O)R.sub.b, —(CH.sub.2).sub.rNR.sub.aC(═O)OR.sub.b, —(CH.sub.2).sub.rNR.sub.aC(═O)NR.sub.aR.sub.a, —(CH.sub.2).sub.rC(═O)R.sub.b, —(CH.sub.2).sub.rC(═O)OR.sub.b, —(CH.sub.2).sub.rOC(═O)R.sub.b, —(CH.sub.2).sub.rC(═O)NR.sub.aR.sub.a, —(CH.sub.2).sub.rOC(═O)R.sub.b, C.sub.3-6cycloalkyl substituted with 0-4 R.sub.e, aryl substituted with 0-4 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-4 R.sub.e; R.sub.6, at each occurrence, is independently selected from H, C.sub.1-3alkyl substituted with 0-4 R.sub.e, —S(O).sub.pR.sub.c, —C(═O)R.sub.b, —C(═O)(CH.sub.2).sub.rNR.sub.aR.sub.a, —C(═O)OR.sub.b, —S(O).sub.pNR.sub.aR.sub.a, —(CH.sub.2).sub.r-aryl substituted with 0-4 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-4 R.sub.e; R.sub.a, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; or R.sub.a and R.sub.a together with the nitrogen atom to which they are both attached form a heterocyclic ring substituted with 0-5 R.sub.e; R.sub.b, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2)-heterocyclyl substituted with 0-5 R.sub.e; R.sub.e, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-6 carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.d, at each occurrence, is independently selected from H and C.sub.1-6 alkyl substituted with 0-5 R.sub.e; R.sub.e, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.f, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, —(CH.sub.2).sub.r—C.sub.3-6 cycloalkyl, —(CH.sub.2).sub.r-aryl, F, Cl, Br, CN, NO.sub.2, ═O, —NH.sub.2, —NHC.sub.1-4alkyl, —N(C.sub.1-4alkyl).sub.2, —C(═O)OH, —C(═O)OC.sub.1-4alkyl, —(CH.sub.2).sub.rOH, and —(CH.sub.2).sub.rOC.sub.1-4alkyl; R.sub.f, at each occurrence, is independently selected from H, F, Cl, Br, CN, OH, C.sub.1-5 alkyl optionally substituted with OH, C.sub.3-6 cycloalkyl, and phenyl; p, at each occurrence, is independently selected from zero, 1, and 2; and r, at each occurrence, is independently selected from zero, 1, 2, 3, and 4.

(50) In a third aspect, the present invention provides a compound of formula (II):

(51) ##STR00015##
or a pharmaceutically acceptable salt thereof, wherein: Ring A is selected from

(52) ##STR00016## R.sub.2 is selected from methyl and —CH.sub.2-cyclopropyl; R.sub.3 is selected from H, F, and —OC.sub.1-4 alkyl; R.sub.4 is selected from

(53) ##STR00017## ##STR00018## ##STR00019## R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, CN, C.sub.1-4alkyl substituted with 0-4 R.sub.e, —(CHR.sub.d).sub.rOR.sub.b, —S(O).sub.pR.sub.c, —S(O).sub.pNR.sub.aR.sub.a, —(CH.sub.2).sub.rNR.sub.aS(O).sub.pR.sub.c, —(CH.sub.2).sub.tNR.sub.aR.sub.a, —(CH.sub.2).sub.rNR.sub.aC(═O)R.sub.b, —NR.sub.aC(═O)OR.sub.b, —NR.sub.aC(═O)NR.sub.aR.sub.a, —(CH.sub.2).sub.rC(═O)R.sub.b, —(CH.sub.2).sub.rC(═O)OR.sub.b, —(CH.sub.2).sub.rC(═O)NR.sub.aR.sub.a, —(CH.sub.2).sub.rOC(═O)R.sub.b, C.sub.3-6cycloalkyl substituted with 0-4 R.sub.e, aryl substituted with 0-4 R.sub.e, and heterocyclyl substituted with 0-4 R.sub.e; R.sub.6, at each occurrence, is independently selected from H, C.sub.1-3alkyl substituted with 0-4 R.sub.e, —S(O).sub.pR.sub.c, —C(═O)R.sub.b, —(CH.sub.2).sub.rC(═O)NR.sub.aR.sub.a, —C(═O)(CH.sub.2).sub.rNR.sub.aC(═O)R.sub.b, —C(═O)OR.sub.b, —S(O).sub.pNR.sub.aR.sub.a, aryl substituted with 0-4 R.sub.e, and heterocyclyl substituted with 0-4 R.sub.e; R.sub.a, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; or R.sub.a and R.sub.a together with the nitrogen atom to which they are both attached form a heterocyclic ring substituted with 0-5 R.sub.e; R.sub.b, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.rC.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.c, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-6 carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.d, at each occurrence, is independently selected from H and C.sub.1-6 alkyl substituted with 0-5 R.sub.e; R.sub.e, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.f, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, —(CH.sub.2).sub.rC.sub.3-6 cycloalkyl, —(CH.sub.2).sub.r-aryl, F, Cl, Br, CN, NO.sub.2, ═O, —NH.sub.2, —NHC.sub.1-4alkyl, —N(C.sub.1-4alkyl).sub.2, —C(═O)OH, —C(═O)OC.sub.1-4alkyl, —(CH.sub.2).sub.rOH, and —(CH.sub.2).sub.rOC.sub.1-4alkyl; R.sub.f, at each occurrence, is independently selected from H, F, Cl, Br, CN, OH, C.sub.1-5 alkyl optionally substituted with OH, C.sub.3-6 cycloalkyl, and phenyl; p, at each occurrence, is independently selected from zero, 1, and 2; and r, at each occurrence, is independently selected from zero, 1, 2, 3, and 4.

(54) In a fourth aspect, the present invention provides a compound of formula (III):

(55) ##STR00020##
or a pharmaceutically acceptable salt thereof, wherein: Ring A is

(56) ##STR00021## R.sub.2 is —CH.sub.2-cyclopropyl; R.sub.3 is —OC.sub.1-4 alkyl; R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, CN, C.sub.1-4alkyl substituted with 0-4 R.sub.e, —(CHR.sub.d).sub.rOR.sub.b, —S(O).sub.pR.sub.c—(CH.sub.2).sub.rNR.sub.aR.sub.a, —(CH.sub.2).sub.rNHC(═O)R.sub.b, —NHC(═O)OR.sub.b, —(CH.sub.2).sub.rNHS(O).sub.pR.sub.c, —(CH.sub.2).sub.rC(═O)NR.sub.aR.sub.a, —(CH.sub.2).sub.rC(═O)OR.sub.b, C.sub.3-6cycloalkyl substituted with 0-4 R.sub.e, aryl substituted with 0-4 R.sub.e, and heterocyclyl substituted with 0-4 R.sub.e; R.sub.a, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; or R.sub.a and R.sub.a together with the nitrogen atom to which they are both attached form a heterocyclic ring substituted with 0-5 R.sub.e; R.sub.b, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.c, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-6 carbocyclyl substituted with 0-5 Re, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.d, at each occurrence, is independently selected from H and C.sub.1-6 alkyl; R.sub.e, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.f, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, —(CH.sub.2).sub.r—C.sub.3-6 cycloalkyl, —(CH.sub.2).sub.r-aryl, F, Cl, Br, CN, NO.sub.2, ═O, —NH.sub.2, —NHC.sub.1-4alkyl, —N(C.sub.1-4alkyl).sub.2, —C(═O)OH, —C(═O)OC.sub.1-4 alkyl, —(CH.sub.2).sub.rOH, —(CH.sub.2).sub.rOC.sub.1-4alkyl, and SO.sub.2C.sub.1-4alkyl; R.sub.f, at each occurrence, is independently selected from H, F, Cl, Br, CN, OH, C.sub.1-5 alkyl optionally substituted with OH, C.sub.3-6 cycloalkyl, and phenyl; p, at each occurrence, is independently selected from zero, 1, and 2; and r, at each occurrence, is independently selected from zero, 1, 2, 3, and 4.

(57) In a fifth aspect, the present invention provides a compound or a pharmaceutically acceptable salt thereof, within the scope of the fourth aspect, wherein: R.sub.3 is —OCH.sub.3; and R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, C.sub.1-4alkyl, —OH, —OC.sub.1-3alkyl, and —NHS(O).sub.2C.sub.2-4alkenyl.

(58) In a sixth aspect, the present invention provides a compound or a pharmaceutically acceptable salt thereof, within the scope of the third aspect, wherein: Ring A is

(59) ##STR00022##
R.sub.2 is —CH.sub.2-cyclopropyl; R.sub.3 is —OC.sub.1-4 alkyl; R.sub.4 is selected from

(60) ##STR00023## R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, CN, C.sub.1-4alkyl substituted with 0-4 R.sub.e, —(CH.sub.2).sub.rOR.sub.b, —S(O).sub.pR.sub.c, —S(O).sub.pNR.sub.aR.sub.a, —(CH.sub.2).sub.rNR.sub.aS(O).sub.pR.sub.c, —(CH.sub.2).sub.rNR.sub.aR.sub.a, —(CH.sub.2).sub.rNR.sub.aC(═O)R.sub.b, —NR.sub.aC(═O)OR.sub.b, —NR.sub.aC(═O)NR.sub.aR.sub.a, —(CH.sub.2).sub.rC(═O)R.sub.b, —(CH.sub.2).sub.rC(═O)OR.sub.b, —(CH.sub.2).sub.rC(═O)NR.sub.aR.sub.a, —(CH.sub.2).sub.rOC(═O)R.sub.b, C.sub.3-6cycloalkyl substituted with 0-4 R.sub.e, aryl substituted with 0-4 R.sub.e, and heterocyclyl substituted with 0-4 R.sub.e; R.sub.a, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6, alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; or R.sub.a and R.sub.a together with the nitrogen atom to which they are both attached form a heterocyclic ring substituted with 0-5 R.sub.e; R.sub.b, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.rC.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.c, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-6 carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.e, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.f, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, —(CH.sub.2).sub.rC.sub.3-6 cycloalkyl, —(CH.sub.2).sub.r-aryl, F, Cl, Br, CN, NO.sub.2, ═O, —NH.sub.2, —NHC.sub.1-4alkyl, —N(C.sub.1-4alkyl).sub.2, —C(═O)OH, —C(═O)OC.sub.1-4alkyl, —(CH.sub.2).sub.rOH, and —(CH.sub.2).sub.rOC.sub.1-4alkyl; R.sub.f, at each occurrence, is independently selected from H, F, Cl, Br, CN, OH, C.sub.1-5 alkyl optionally substituted with OH, C.sub.3-6 cycloalkyl, and phenyl; p, at each occurrence, is independently selected from zero, 1, and 2; and r, at each occurrence, is independently selected from zero, 1, 2, 3, and 4.

(61) In a seventh aspect, the present invention provides a compound or a pharmaceutically acceptable salt thereof, within the scope of the sixth aspect, wherein: R.sub.3 is —CH.sub.3; and R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, C.sub.1-4alkyl, —OH, —OC.sub.1-3alkyl, and —NHS(O).sub.2C.sub.2-4alkenyl.

(62) In an eighth aspect, the present invention provides a compound or a pharmaceutically acceptable salt thereof, within the scope of the third aspect, wherein: Ring A is

(63) ##STR00024## R.sub.2 is —CH.sub.2-cyclopropyl; R.sub.3 is —OC.sub.1-4 alkyl; R.sub.4 is selected from

(64) ##STR00025## ##STR00026## R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, CN C.sub.1-4alkyl, —OR.sub.b, —S(O).sub.pR.sub.c—(CH.sub.2).sub.rNR.sub.aR.sub.a, —(CH.sub.2).sub.rNR.sub.aC(═O)R.sub.b, —NR.sub.aC(═O)OR.sub.b, —(CH.sub.2).sub.rNR.sub.aS(O).sub.pR.sub.c, —C(═O)NR.sub.aR.sub.a, —C(═O)OR.sub.b, C.sub.3-6cycloalkyl substituted with 0-4 R.sub.e, aryl substituted with 0-4 R.sub.e, and heterocyclyl substituted with 0-4 R.sub.e; R.sub.6, at each occurrence, is independently selected from H, C.sub.1-3alkyl substituted with 0-4 R.sub.e, —S(O).sub.pR.sub.c, —C(═O)R.sub.b, —(CH.sub.2).sub.rC(═O)NR.sub.aR.sub.a, —C(═O)(CH.sub.2).sub.rNR.sub.aC(═O)R.sub.b, —C(═O)OR.sub.b, —S(O).sub.pNR.sub.aR.sub.a, aryl substituted with 0-4 R.sub.e, and heterocyclyl substituted with 0-4 R.sub.e; R.sub.a, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; or R.sub.a and R.sub.a together with the nitrogen atom to which they are both attached form a heterocyclic ring substituted with 0-5 R.sub.e; R.sub.b, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.rC.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.c, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-6 carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.e, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.f, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, —(CH.sub.2).sub.rC.sub.3-6 cycloalkyl, —(CH.sub.2).sub.r-aryl, F, Cl, Br, CN, NO.sub.2, ═O, —NH.sub.2, —NHC.sub.1-4alkyl, —N(C.sub.1-4alkyl).sub.2, —C(═O)OH, —C(═O)OC.sub.1-4alkyl, —(CH.sub.2).sub.rOH, and —(CH.sub.2).sub.rOC.sub.1-4alkyl; R.sub.f, at each occurrence, is independently selected from H, F, Cl, Br, CN, OH, C.sub.1-5 alkyl optionally substituted with OH, C.sub.3-6 cycloalkyl, and phenyl; p, at each occurrence, is independently selected from zero, 1, and 2; and r, at each occurrence, is independently selected from zero, 1, 2, 3, and 4.

(65) In a ninth aspect, the present invention provides a compound or a pharmaceutically acceptable salt thereof, within the scope of the eighth aspect, wherein: R.sub.4 is selected from

(66) ##STR00027## R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, C.sub.1-4alkyl, and OH.

(67) In a tenth aspect, the present invention provides a compound of formula (IV):

(68) ##STR00028##
or a pharmaceutically acceptable salt thereof, within the scope of the ninth aspect,

(69) wherein: Ring A is

(70) ##STR00029## R.sub.2 is selected from methyl and —CH.sub.2-cyclopropyl; R.sub.3 is selected from H, F, and —OC.sub.1-4 alkyl; R.sub.4 is selected from

(71) ##STR00030## R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, CN, C.sub.1-4alkyl, —(CH.sub.2).sub.rOR.sub.b, —NR.sub.aR.sub.a, —NR.sub.aC(═O)R.sub.b, —NR.sub.aC(═O)OR.sub.b, —C(═O)OR.sub.b, NR.sub.aS(O).sub.pR.sub.c, —C(═O)NR.sub.aR.sub.a, —NR.sub.aC(═O)NR.sub.aR.sub.a, C.sub.3-6cycloalkyl substituted with 0-4 R.sub.e, aryl substituted with 0-4 R.sub.e, and heterocyclyl substituted with 0-4 R.sub.e; R.sub.6, at each occurrence, is independently selected from H and C.sub.1-3alkyl; R.sub.a, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.b, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.c, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-6 carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.d, at each occurrence, is independently selected from H and C.sub.1-3 alkyl; R.sub.e, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.f, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, —(CH.sub.2).sub.rC.sub.3-6 cycloalkyl, —(CH.sub.2).sub.r-aryl, F, Cl, Br, CN, NO.sub.2, ═O, N(C.sub.1-4alkyl).sub.2, —C(═O)OH, —C(═O)OC.sub.1-4alkyl, —(CH.sub.2).sub.rOH, and —(CH.sub.2).sub.rOC.sub.1-4alkyl; R.sub.f, at each occurrence, is independently selected from H, F, Cl, Br, CN, OH, C.sub.1-5 alkyl optionally substituted with OH, C.sub.3-6 cycloalkyl, and phenyl; p, at each occurrence, is independently selected from zero, 1, and 2; and r, at each occurrence, is independently selected from zero, 1, 2, 3, and 4.

(72) In an eleventh aspect, the present invention provides a compound or a pharmaceutically acceptable salt thereof, within the scope of the tenth aspect, wherein: R.sub.2 is CH.sub.2-cyclopropyl; R.sub.3 is —OCH.sub.3; R.sub.4 is

(73) ##STR00031## R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, C.sub.1-4alkyl, and —(CH.sub.2).sub.0-1OH; and R.sub.d is H.

(74) In a twelfth aspect, the present invention provides a compound or a pharmaceutically acceptable salt thereof, within the scope of the second aspect, wherein: L is —C(═O)NH—; R.sub.2 is —CH.sub.2-cyclopropyl; R.sub.3 is —OC.sub.1-4 alkyl; R.sub.4 is selected from

(75) ##STR00032## R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, C.sub.1-4alkyl, —OH, and —CN; and R.sub.6, at each occurrence, is independently selected from H and C.sub.1-3alkyl.

(76) In a thirteenth aspect, the present invention provides a compound or a pharmaceutically acceptable salt thereof, within the scope of the second aspect, wherein: L is —O—; R.sub.2 is —CH.sub.2-cyclopropyl; R.sub.3 is —OC.sub.1-4 alkyl; R.sub.4 is selected from

(77) ##STR00033##
and R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, C.sub.1-4alkyl, —OH, and —CN.

(78) In a fourteenth aspect, the present invention provides a compound of Formula (I):

(79) ##STR00034##
or a pharmaceutically acceptable salt thereof, wherein: Q is selected from N and CH; Ring A is 4- to 15-membered heterocyclyl substituted with 1-4 R.sub.7; R.sub.1 is selected from CH.sub.3, CD.sub.3, and —CH.sub.2-5 membered heterocyclyl compring carbon atoms and 1-3 heteroatoms selected from N, NC.sub.1-4alkyl, O, and S; R.sub.2 is selected from H, C.sub.1-3 alkyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r—C.sub.3-6 cycloalkyl substituted with 0-5 R.sub.e; R.sub.3 is selected from H, F, Cl, Br, —OR.sub.b, and C.sub.1-3 alkyl substituted with 0-5 R.sub.e; L is absent or selected from —NR.sub.d—, —O—, —C(═O)NR.sub.d—, and —S(O).sub.p—; R.sub.4 is selected from —(CH.sub.2).sub.r-aryl substituted with 1-7 R.sub.5, —(CH.sub.2).sub.r—C.sub.3-12 cycloalkyl (substituted with 1-2 OR.sub.b, C(═O)OR.sub.b, —C(═O)NR.sub.aR.sub.a, —NR.sub.aC(═O)R.sub.b), —(CH.sub.2).sub.r-heterocyclyl comprising carbon atoms and 1-3 heteroatoms selected from N, NR.sub.6, O, and S and substituted with 1-7 R.sub.5; R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, CN, ═O, nitro, C.sub.1-4alkyl substituted with 0-5 R.sub.e, C.sub.2-4alkenyl substituted with 0-5 R.sub.e, C.sub.2-4alkynyl substituted with 0-5 R.sub.e, —(CHR.sub.d).sub.rOR.sub.b, —(CHR.sub.d).sub.rS(O).sub.pR.sub.c, —(CHR.sub.d).sub.rS(O).sub.pNR.sub.aR.sub.a, —(CHR.sub.d).sub.rNR.sub.aS(O).sub.pR.sub.c, (CHR.sub.d)NR.sub.aR.sub.a, —(CHR.sub.d).sub.rNR.sub.aC(═O)R.sub.b, —(CHR.sub.d).sub.rNR.sub.aC(═O)OR.sub.b, —(CHR.sub.d).sub.rC(═O)NR.sub.aR.sub.a, —(CHR.sub.d).sub.rC(═O)R.sub.b, —(CHR.sub.d).sub.rC(═O)OR.sub.b, —(CHR.sub.d).sub.rC(═O)NR.sub.aR.sub.a, —(CHR.sub.d).sub.rOC(═O)R.sub.b, —(CHR.sub.d).sub.rOC(═O)OR.sub.b, —(CHR.sub.d).sub.rO(CH.sub.2).sub.rC(═O)NR.sub.aR.sub.a, C.sub.3-6cycloalkyl substituted with 0-4 R.sub.e, aryl substituted with 0-4 R.sub.e, and heterocyclyl substituted with 0-4 R.sub.e; R.sub.6 is selected from H, C.sub.1-3alkyl substituted with 0-4 R.sub.e, —S(O).sub.pR.sub.c, —(CH.sub.2).sub.rC(═O)R.sub.b, —(CH.sub.2).sub.r C(═O)OR.sub.b, —(CH.sub.2).sub.rC(═O)(CH.sub.2).sub.rNR.sub.aR.sub.a, —C(═O)(CH.sub.2).sub.rNR.sub.aC(═O)R.sub.b, —S(O).sub.pNR.sub.aR.sub.a, —(CH.sub.2).sub.r—C.sub.3-6cycloalkyl substituted with 0-4 R.sub.e, —(CH.sub.2).sub.r-aryl substituted with 0-4 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-4 R.sub.e; R.sub.7 is selected from H, F, Cl, CN, C.sub.1-3 alkyl, ═N—OR.sub.b, —(CH.sub.2).sub.rOR.sub.b, —(CH.sub.2).sub.rNR.sub.aR.sub.a, —NR.sub.aC(═NH)C.sub.1-3alkyl, —NR.sub.aC(═O)OR.sub.b, carbocyclyl, and heterocyclyl; alternatively, two R.sub.7 groups are taken together to form carbocyclyl or heterocyclyl; R.sub.8, at each occurrence, is independently selected from H, F, Cl, Br, and C.sub.1-4alkyl substituted with 0-5 R.sub.e; R.sub.a, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; or R.sub.a and R.sub.a together with the nitrogen atom to which they are both attached form a heterocyclic ring substituted with 0-5 R.sub.e; R.sub.b, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.c, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-6 carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e: R.sub.d, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, and OH, R.sub.e, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.f, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, —(CH.sub.2).sub.rC.sub.3-6 cycloalkyl, —(CH.sub.2).sub.r-aryl, —(CH.sub.2).sub.r-heterocyclyl, Si(C.sub.1-4alkyl).sub.3, F, Cl, Br, CN, NO.sub.2, ═O, CO.sub.2H, —(CH.sub.2).sub.tOR.sub.f, S(O).sub.pR.sub.f, C(═O)NR.sub.fR.sub.f, S(O).sub.pNR.sub.fR.sub.f, and —(CH.sub.2).sub.rNR.sub.fR.sub.f; R.sub.f, at each occurrence, is independently selected from H, F, Cl, Br, CN, OH, C.sub.1-5 alkyl optionally substituted with OH, C.sub.2-5 alkenyl, C.sub.2-5 alkynyl, C.sub.3-6 cycloalkyl, and phenyl, or R.sub.f and R.sub.f together with the nitrogen atom to which they are both attached form a heterocyclic ring optionally substituted with C.sub.1-4alkyl; p, at each occurrence, is independently selected from zero, 1, and 2; r, at each occurrence, is independently selected from zero, 1, 2, 3, and 4; provided: (1) when L is absent, R.sub.4 is not

(80) ##STR00035## (2) when L is —NR.sub.d—, R.sub.4 is not

(81) ##STR00036##
and (3) when L is —O—, R.sub.4 is not C.sub.3-6 cycloalkyl.

(82) In a fifteenth aspect, the present invention provides a compound or a pharmaceutically acceptable salt thereof, within the scope of the fourteenth aspect, wherein:

(83) ##STR00037##
is selected from

(84) ##STR00038## R.sub.1 is selected from CH.sub.3 and CD.sub.3; R.sub.2 is selected from methyl, ethyl and —CH.sub.2-cyclopropyl substituted with 0-3 R.sub.e; R.sub.3 is selected from H, F, Cl, Br, and —OC.sub.1-4 alkyl; L is absent or selected from —NR.sub.d—, —O—, —C(═O)NH—, —S—, and —S(O).sub.2—; R.sub.a is selected from

(85) ##STR00039## ##STR00040## ##STR00041## ##STR00042## ##STR00043## ##STR00044## R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, CN, ═O, C.sub.1-4alkyl substituted with 0-5 R.sub.e, C.sub.2-4alkenyl, C.sub.2-4alkynyl, —(CHR.sub.d).sub.rOR.sub.b, —(CH.sub.2).sub.rS(O).sub.pR.sub.c, —(CH.sub.2).sub.rS(O).sub.pNR.sub.aR.sub.a, —(CH.sub.2).sub.rNR.sub.aS(O).sub.pR.sub.c, —(CH.sub.2)NR.sub.aR.sub.a, —(CH.sub.2).sub.rNR.sub.aC(═O)R.sub.b, —(CH.sub.2).sub.rNR.sub.aC(═O)OR.sub.b, —(CH.sub.2).sub.rNR.sub.aC(═O)NR.sub.aR.sub.a, —(CH.sub.2).sub.rC(═O)R.sub.b, —(CH.sub.2).sub.rC(═O)OR.sub.b, —(CHR.sub.d).sub.rC(═O)NR.sub.aR.sub.a, —(CH.sub.2).sub.rOC(═O)R.sub.b, —(CH.sub.2).sub.rOC(═O)OR.sub.b, —(CH.sub.2).sub.rO(CH.sub.2).sub.rC(═O)NR.sub.aR.sub.a, C.sub.3-6cycloalkyl substituted with 0-4 R.sub.e, aryl substituted with 0-4 R.sub.e, and heterocyclyl substituted with 0-4 R.sub.e; R.sub.6, at each occurrence, is independently selected from H, C.sub.1-3alkyl substituted with 0-4 R.sub.e, —S(O).sub.pR.sub.c, —C(═O)R.sub.b, —(CH.sub.2).sub.rC(═O)OR.sub.b, —(CH.sub.2).sub.rC(═O)(CH.sub.2).sub.rNR.sub.aR.sub.a, —C(═O)(CH.sub.2).sub.rNR.sub.aC(═O)R.sub.b, —S(O).sub.pNR.sub.aR.sub.a, —(CH.sub.2).sub.r-aryl substituted with 0-4 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-4 R.sub.e; R.sub.a, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.f, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; or R.sub.a and R.sub.a together with the nitrogen atom to which they are both attached form a heterocyclic ring substituted with 0-5 R.sub.e; R.sub.b, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.c, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-6 carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e: R.sub.d, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, and OH; R.sub.e, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.f, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, —(CH.sub.2).sub.rC.sub.3-6 cycloalkyl, —(CH.sub.2).sub.r-aryl, —(CH.sub.2).sub.r-heterocyclyl, F, Cl, Br, CN, NO.sub.2, ═O, —NH.sub.2, —NHC.sub.1-4alkyl, —N(C.sub.1-4alkyl).sub.2, —C(═O)OH, —C(═O)OC.sub.1-4alkyl, —(CH.sub.2).sub.rOH, and —(CH.sub.2).sub.rOC.sub.1-4alkyl; R.sub.f, at each occurrence, is independently selected from H, F, Cl, Br, CN, OH, C.sub.1-5 alkyl optionally substituted with OH, C.sub.3-6 cycloalkyl, and phenyl; p, at each occurrence, is independently selected from zero, 1, and 2; and r, at each occurrence, is independently selected from zero, 1, 2, 3, and 4.

(86) In a sixteenth aspect, the present invention provides a compound of Formula (II):

(87) ##STR00045##
or a pharmaceutically acceptable salt thereof, within the scope of the fifteenth aspect, wherein:

(88) ##STR00046##
is selected from

(89) ##STR00047## R.sub.2 is selected from CH.sub.3, CH.sub.2CH.sub.3 and —CH.sub.2-cyclopropyl substituted with 0-2 F, Cl, and CH.sub.3; R.sub.3 is selected from H, F, and —OC.sub.1-4 alkyl; R.sub.4 is selected from

(90) ##STR00048## ##STR00049## ##STR00050## ##STR00051## R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, CN, ═O, C.sub.1-4alkyl substituted with 0-4 R.sub.e, —(CHR.sub.d).sub.rOR.sub.b, —(CH.sub.2).sub.rS(O).sub.pR.sub.c, —S(O).sub.pNR.sub.aR.sub.a, —(CH.sub.2).sub.rNR.sub.aS(O).sub.pR.sub.c, —(CH.sub.2).sub.rNR.sub.aR.sub.a, —(CH.sub.2).sub.rNR.sub.aC(═O)R.sub.b, —NR.sub.aC(═O)OR.sub.b, —NR.sub.aC(═O)NR.sub.aR.sub.a, —(CH.sub.2).sub.rC(═O)R.sub.b, —(CH.sub.2).sub.rC(═O)OR.sub.b, —(CHR.sub.d).sub.rC(═O)NR.sub.aR.sub.a, —(CH.sub.2).sub.rOC(═O)R.sub.b, —(CH.sub.2).sub.rOC(═O)OR.sub.b, —(CH.sub.2)O(CH.sub.2).sub.rC(═O)NR.sub.aR.sub.a, C.sub.3-6cycloalkyl substituted with 0-4 R.sub.e, aryl substituted with 0-4 R.sub.e, and heterocyclyl substituted with 0-4 R.sub.e; R.sub.6, at each occurrence, is independently selected from H, C.sub.1-3alkyl substituted with 0-4 R.sub.e, —S(O).sub.pR.sub.c, —C(═O)R.sub.b, —(CH.sub.2).sub.rC(═O)OR.sub.b, —(CH.sub.2).sub.rC(═O)NR.sub.aR.sub.a, —C(═O)(CH.sub.2).sub.rNR.sub.aC(═O)R.sub.b, —S(O).sub.pNR.sub.aR.sub.a, aryl substituted with 0-4 R.sub.e, and heterocyclyl substituted with 0-4 R.sub.e; R.sub.a, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; or R.sub.a and R.sub.a together with the nitrogen atom to which they are both attached form a heterocyclic ring substituted with 0-5 R.sub.e; R.sub.b, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.rC.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.c, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-6 carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e: R.sub.d, at each occurrence, is independently selected from H and C.sub.1-6 alkyl substituted with 0-5 R.sub.e; R.sub.e, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.f, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, —(CH.sub.2).sub.rC.sub.3-6 cycloalkyl, —(CH.sub.2).sub.r-aryl, —(CH.sub.2).sub.r-heterocyclyl, F, Cl, Br, CN, NO.sub.2, ═O, —NH.sub.2, —NHC.sub.1-4alkyl, —N(C.sub.1-4alkyl).sub.2, —C(═O)OH, —C(═O)OC.sub.1-4alkyl, —(CH.sub.2).sub.rOH, and —(CH.sub.2).sub.rOC.sub.1-4alkyl; R.sub.f, at each occurrence, is independently selected from H, F, Cl, Br, CN, OH, C.sub.1-5 alkyl optionally substituted with OH, C.sub.3-6 cycloalkyl, and phenyl; p, at each occurrence, is independently selected from zero, 1, and 2; and r, at each occurrence, is independently selected from zero, 1, 2, 3, and 4.

(91) In a seventeenth aspect, the present invention provides a compound of Formula (III):

(92) ##STR00052##
or a pharmaceutically acceptable salt thereof, within the scope of the sixteenth aspect, wherein:

(93) ##STR00053##
is selected from

(94) ##STR00054## R.sub.2 is —CH.sub.2-cyclopropyl; R.sub.3 is —OC.sub.1-4 alkyl; R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, CN, C.sub.1-4alkyl substituted with 0-4 R.sub.e, —(CHR.sub.d).sub.rOR.sub.b, —(CH.sub.2).sub.rS(O).sub.pR.sub.c, —S(O).sub.pNR.sub.aR.sub.a, —(CH.sub.2).sub.rNHS(O).sub.pR.sub.c, —(CH.sub.2).sub.rNR.sub.aR.sub.a, —(CH.sub.2).sub.rNHC(═O)R.sub.b, —NHC(═O)OR.sub.b, —(CHR.sub.d).sub.rC(═O)NR.sub.aR.sub.a, —(CH.sub.2).sub.rC(═O)OR.sub.b, —OC(═O)OR.sub.b, —O(CH.sub.2).sub.0-1C(═O)NR.sub.aR.sub.a, C.sub.3-6cycloalkyl substituted with 0-4 R.sub.e, aryl substituted with 0-4 R.sub.e, and heterocyclyl substituted with 0-4 R.sub.e; R.sub.a, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; or R.sub.a and R.sub.a together with the nitrogen atom to which they are both attached form a heterocyclic ring substituted with 0-5 R.sub.e; R.sub.b, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.rC.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.c, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-6 carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.d, at each occurrence, is independently selected from H, C.sub.1-4 alkyl, and OH; R.sub.e, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.f, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, —(CH.sub.2).sub.rC.sub.3-6 cycloalkyl, —(CH.sub.2)-aryl, —(CH.sub.2).sub.r-heterocyclyl, F, Cl, Br, CN, NO.sub.2, ═O, —NH.sub.2, —NHC.sub.1-4alkyl, —N(C.sub.1-4alkyl).sub.2, —C(═O)OH, —C(═O)OC.sub.1-4alkyl, —(CH.sub.2).sub.rOH, —(CH.sub.2).sub.rOC.sub.1-4alkyl, and SO.sub.2C.sub.1-4alkyl; R.sub.f, at each occurrence, is independently selected from H, F, Cl, Br, CN, OH, C.sub.1-5 alkyl optionally substituted with OH, C.sub.3-6 cycloalkyl, and phenyl; p, at each occurrence, is independently selected from zero, 1, and 2; and r, at each occurrence, is independently selected from zero, 1, 2, 3, and 4.

(95) In an eighteenth aspect, the present invention provides a compound or a pharmaceutically acceptable salt thereof, within the scope of the seventeenth aspect, wherein: R.sub.3 is —OCH.sub.3; R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, CN, C.sub.1-4alkyl, —(CH.sub.2).sub.0-1OR.sub.b, —S(O).sub.2NH.sub.2, —NHS(O).sub.2C.sub.1-3 alkyl, —NHS(O).sub.2C.sub.2-4alkenyl, —NHC(═O)R.sub.b, —C(═O)NH.sub.2 and heterocyclyl selected from

(96) ##STR00055## R.sub.b, at each occurrence, is independently selected from H and C.sub.1-6 alkyl substituted with 0-5 R.sub.e, R.sub.e, at each occurrence, is independently selected from C.sub.1-6 alkyl, F, Cl, Br, CN, NO.sub.2, ═O, —NH.sub.2, —NHC.sub.1-4alkyl, —N(C.sub.1-4alkyl).sub.2, —C(═O)OH, —C(═O)OC.sub.1-4alkyl, —(CH.sub.2).sub.rOH, —(CH.sub.2).sub.rOC.sub.1-4alkyl, and SO.sub.2C.sub.1-4alkyl;

(97) In a nineteenth aspect, the present invention provides a compound or a pharmaceutically acceptable salt thereof, within the scope of the sixteenth aspect, wherein:

(98) ##STR00056##
is selected from

(99) ##STR00057## R.sub.2 is —CH.sub.2-cyclopropyl; R.sub.3 is —OC.sub.1-4 alkyl; R.sub.4 is selected from

(100) ##STR00058## R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, CN, C.sub.1-4alkyl substituted with 0-4 R.sub.e, —(CH.sub.2).sub.rOR.sub.b, —S(O).sub.pR.sub.c, —S(O).sub.pNR.sub.aR.sub.a, —(CH.sub.2).sub.rNR.sub.aS(O).sub.pR.sub.c, —(CH.sub.2).sub.rNR.sub.aR.sub.a, —(CH.sub.2).sub.rNR.sub.aC(═O)R.sub.b, —NR.sub.aC(═O)OR.sub.b, —NR.sub.aC(═O)NR.sub.aR.sub.a, —(CH.sub.2).sub.rC(═O)R.sub.b, —(CH.sub.2).sub.rC(═O)OR.sub.b, —(CH.sub.2).sub.rC(═O)NR.sub.aR.sub.a, —(CH.sub.2).sub.rOC(═O)R.sub.b, C.sub.3-6cycloalkyl substituted with 0-4 R.sub.e, aryl substituted with 0-4 R.sub.e, and heterocyclyl substituted with 0-4 R.sub.e; R.sub.a, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; or R.sub.a and R.sub.a together with the nitrogen atom to which they are both attached form a heterocyclic ring substituted with 0-5 R.sub.e; R.sub.b, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.c, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-6 carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.e, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.f, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, —(CH.sub.2).sub.r—C.sub.3-6 cycloalkyl, —(CH.sub.2).sub.r-aryl, F, Cl, Br, CN, NO.sub.2, ═O, —NH.sub.2, —NHC.sub.1-4alkyl, —N(C.sub.1-4alkyl).sub.2, —C(═O)OH, —C(═O)OC.sub.1-4alkyl, —(CH.sub.2).sub.rOH, and —(CH.sub.2).sub.rOC.sub.1-4alkyl, R.sub.f, at each occurrence, is independently selected from H, F, Cl, Br, CN, OH, C.sub.1-5 alkyl optionally substituted with OH, C.sub.3-6 cycloalkyl, and phenyl; p, at each occurrence, is independently selected from zero, 1, and 2; and r, at each occurrence, is independently selected from zero, 1, 2, 3, and 4.

(101) In a twentieth aspect, the present invention provides a compound or a pharmaceutically acceptable salt thereof, within the scope of the nineteenth aspect, wherein: R.sub.a is —OCH.sub.3; R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, C.sub.1-4alkyl, —OH, —OC.sub.1-3alkyl, —NHS(O).sub.2C.sub.2-4alkenyl, NHC(═O)OC.sub.1-4 alkyl, C(═O)NH.sub.2, C(═O)NHC.sub.1-4alkyl, and heterocyclyl selected from

(102) ##STR00059##
and R.sub.e, at each occurrence, is independently selected from C.sub.1-6 alkyl, F, Cl, Br, CN, NO.sub.2, ═O, —NH.sub.2, —NHC.sub.1-4alkyl, —N(C.sub.1-4alkyl).sub.2, —C(═O)OH, —C(═O)OC.sub.1-4alkyl, —(CH.sub.2).sub.rOH, —(CH.sub.2).sub.rOC.sub.1-4alkyl, and SO.sub.2C.sub.1-4alkyl;

(103) In a twenty first aspect, the present invention provides a compound or a pharmaceutically acceptable salt thereof, within the scope of the sixteenth aspect, wherein:

(104) ##STR00060##
is selected from

(105) ##STR00061## R.sub.2 is —CH.sub.2-cyclopropyl; R.sub.3 is —OC.sub.1-4 alkyl; R.sub.4 is selected from

(106) ##STR00062## ##STR00063## ##STR00064## R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, CN C.sub.1-4alkyl, —OR.sub.b, —S(O).sub.pR.sub.c—(CH.sub.2).sub.rNR.sub.aS(O).sub.pR.sub.c, —(CH.sub.2).sub.rNR.sub.aR.sub.a, —(CH.sub.2).sub.rNR.sub.aC(═O)R.sub.b, —NR.sub.aC(═O)OR.sub.b, —C(═O)OR.sub.b, C(═O)NR.sub.aR.sub.a, C.sub.3-6cycloalkyl substituted with 0-4 R.sub.e, aryl substituted with 0-4 R.sub.e, and heterocyclyl substituted with 0-4 R.sub.e; R.sub.6, at each occurrence, is independently selected from H, C.sub.1-3alkyl substituted with 0-4 R.sub.e, —S(O).sub.pR.sub.c, —C(═O)R.sub.b, —C(═O)OR.sub.b, —(CH.sub.2).sub.rC(═O)NR.sub.aR.sub.a, —C(═O)(CH.sub.2).sub.rNR.sub.aC(═O)R.sub.b, —S(O).sub.pNR.sub.aR.sub.a, aryl substituted with 0-4 R.sub.e, and heterocyclyl substituted with 0-4 R.sub.e, R.sub.a, at each occurrence, is independently selected from H, C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; or R.sub.a and R.sub.a together with the nitrogen atom to which they are both attached form a heterocyclic ring substituted with 0-5 R.sub.e; R.sub.b, at each occurrence, is independently selected from H, C.sub.1-5 alkyl substituted with 0-5 R.sub.e, C.sub.2-6 alkenyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.rC.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-10carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.c, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.e, C.sub.2-6alkenyl substituted with 0-5 R.sub.e, C.sub.2-6 alkynyl substituted with 0-5 R.sub.e, —(CH.sub.2).sub.r—C.sub.3-6 carbocyclyl substituted with 0-5 R.sub.e, and —(CH.sub.2).sub.r-heterocyclyl substituted with 0-5 R.sub.e; R.sub.e, at each occurrence, is independently selected from C.sub.1-6 alkyl substituted with 0-5 R.sub.f, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, —(CH.sub.2).sub.r—C.sub.3-6 cycloalkyl, —(CH.sub.2).sub.r-aryl, F, Cl, Br, CN, NO.sub.2, ═O, —NH.sub.2, —NHC.sub.1-4alkyl, —N(C.sub.1-4alkyl).sub.2, —C(═O)OH, —C(═O)OC.sub.1-4alkyl, —(CH.sub.2).sub.rOH, and —(CH.sub.2).sub.rOC.sub.1-4alkyl: R.sub.f, at each occurrence, is independently selected from H, F, Cl, Br, CN, OH, C.sub.1-5 alkyl optionally substituted with OH, C.sub.3-6 cycloalkyl, and phenyl; p, at each occurrence, is independently selected from zero, 1, and 2; and r, at each occurrence, is independently selected from zero, 1, 2, 3, and 4.

(107) In a twenty second aspect, the present invention provides a compound or a pharmaceutically acceptable salt thereof, within the scope of the twenty first aspect, wherein: R.sub.4 is selected from

(108) ##STR00065## R.sub.5, at each occurrence, is independently selected from H, F, Cl, Br, C.sub.1-4alkyl, OH, and —C(═O)OH.

(109) In a twenty third aspect, the present invention provides a compound of Formula (V):

(110) ##STR00066##
or a pharmaceutically acceptable salt thereof, wherein:

(111) ##STR00067##
is selected from

(112) ##STR00068## R.sub.2 is —CH.sub.2-cyclopropyl; R.sub.3 is —OCH.sub.3; and R.sub.4 is selected from

(113) ##STR00069##

(114) In a twenty fourth aspect, the present invention provides a compound of Formula (VI):

(115) ##STR00070##
or a pharmaceutically acceptable salt thereof, wherein:

(116) ##STR00071##
is selected from

(117) ##STR00072## R.sub.2 is —CH.sub.2-cyclopropyl; R.sub.4 is selected from

(118) ##STR00073##
and R.sub.5 is selected from H, OH, CH.sub.2OH, and —C(CH.sub.3).sub.2OH.

(119) In a twenty fifth aspect, the present invention provides a compound of Formula (VII):

(120) ##STR00074##
or a pharmaceutically acceptable salt thereof, wherein:

(121) ##STR00075##
is selected from

(122) ##STR00076## R.sub.2 is —CH.sub.2-cyclopropyl; R.sub.4 is selected from

(123) ##STR00077## R.sub.5, at each occurrence, is independently selected from F, Cl, C.sub.1-4alkyl, —(CH.sub.2).sub.rOR.sub.b, —S(O).sub.2NR.sub.aR.sub.a, —NR.sub.aS(O).sub.2R.sub.c, and —C(═O)NR.sub.aR.sub.a; R.sub.6, at each occurrence, is independently selected from H and C.sub.1-3alkyl; R.sub.a, at each occurrence, is independently selected from H and C.sub.1-4 alkyl substituted with 0-5 R.sub.e; R.sub.b, at each occurrence, is independently selected from H and C.sub.1-4 alkyl substituted with 0-5 R.sub.e; R.sub.c, at each occurrence, is independently C.sub.1-4 alkyl substituted with 0-5 R.sub.e; R.sub.e, at each occurrence, is independently selected from F, Cl, Br, —OH, and —OC.sub.1-4alkyl; and r, at each occurrence, is independently selected from zero, 1, and 2.

(124) In one embodiment, the present invention provides compounds with IC.sub.50 values≤4.000 μM, using the RFMS PAD4 functional assay disclosed herein, preferably, IC.sub.50 values≤1.000 μM, preferably, IC.sub.50 values≤0.500 μM, preferably, IC.sub.50 values≤0.100 μM, more preferably, IC.sub.50 values≤0.050 μM, more preferably, IC.sub.50 values≤0.03 μM, more preferably, IC.sub.50 values≤0.02 μM, even more preferably, IC.sub.50 values≤0.01 μM.

(125) As defined above and described herein, R.sub.1 is selected from CH.sub.3 and CD.sub.3. In some embodiments, R.sub.1 is CH.sub.3. In some embodiments, R.sub.1 is CD.sub.3.

(126) As defined above and described herein, R.sub.2 is hydrogen, C.sub.1-3 alkyl substituted with 0-5 R.sub.e, or C.sub.3-6 cycloalkyl substituted with 0-5 R.sub.e. In some embodiments, R.sub.2 is hydrogen. In some embodiments, R.sub.2 is C.sub.1-2 alkyl substituted with C.sub.3-6 cycloalkyl. In some embodiments, R.sub.2 is C.sub.3-6 cycloalkyl. In some embodiments, R.sub.2 is methyl. In some embodiments, R.sub.2 is ethyl. In some embodiments, R.sub.2 is cyclopropyl. In some embodiments, R.sub.2 is cyclobutyl. In some embodiments, R.sub.2 is cyclopentyl. In some embodiments, R.sub.2 is cyclohexyl. In some embodiments, R.sub.2 is cyclopropylmethyl. In some embodiments, R.sub.2 is cyclobutylmethyl. In some embodiments, R.sub.2 is cyclopentylmethyl. In some embodiments, R.sub.2 is cyclohexylmethyl. In some embodiments, R.sub.2 is cyclopropylethyl. In some embodiments, R.sub.2 is cyclobutylethyl. In some embodiments, R.sub.2 is cyclopentylethyl. In some embodiments, R.sub.2 is cyclohexylethyl. In some embodiments, R.sub.2 is —CH.sub.2-cyclopropyl or —CH.sub.2-cyclobutyl. In some embodiments, R.sub.2 is —CH.sub.2-cyclobutyl optionally substituted with methyl and —OH. In certain embodiments, R.sub.2 is selected from those functional groups depicted in the examples below.

(127) As defined above and described herein, Q is N or CH. In some embodiments, Q is N. In some embodiments, Q is CH. In certain embodiments, Q is selected from those functional groups depicted in the examples below.

(128) As defined above and described herein, R.sub.3 is selected from H, F, Cl, Br, —OR.sub.b, and C.sub.1-3 alkyl substituted with 0-5 R.sub.e. In some embodiments, R.sub.3 is H. In some embodiments, R.sub.3 is F, Cl, Br. In some embodiments, R.sub.3 is F, In some embodiments, R.sup.3 is C.sub.1-3 alkyl. In some embodiments, R.sub.3 is methyl. In some embodiments, R.sub.3 is ethyl. In some embodiments, R.sub.3 is propyl. In some embodiments, R.sub.3 is OR.sub.b. In some embodiments, R.sub.3 is —OCH.sub.3. In some embodiments, R.sub.3 is —OCH.sub.2CH.sub.3. In some embodiments, R.sub.3 is —OCH.sub.2CH.sub.2CH.sub.3. In certain embodiments, R.sub.3 is —OCH(F).sub.2. In certain embodiments, R.sub.3 is selected from those functional groups depicted in the examples below.

(129) As defined above and described herein, L is absent, —NR.sub.d—, —O—, —C(═O)NR.sub.d—, or —S(O).sub.p—; in some embodiments, L is absent. In some embodiments, L is —NR.sub.d—, R.sub.d is H or C.sub.1-3alkyl. In some embodiments, L is —O—. In some embodiments, L is —C(═O)NH—. In some embodiments, L is —S(O).sub.2—. In some embodiments, L is —S—. In certain embodiments, L is selected from those functional groups depicted in the examples below.

(130) As defined above and described herein, each R.sub.4 is

(131) ##STR00078## ##STR00079## ##STR00080##

(132) In some embodiments, R.sub.4 is

(133) ##STR00081##
In some embodiments, R.sub.4 is

(134) ##STR00082##
In some embodiments, R.sub.4 is

(135) ##STR00083##
In some embodiments, R.sub.4 is

(136) ##STR00084##

(137) In some embodiments, R.sub.4 is

(138) ##STR00085##

(139) In some embodiments, R.sub.4 is

(140) ##STR00086##
In some embodiments, R.sub.4 is

(141) ##STR00087##
In some embodiments, R.sub.4 is

(142) ##STR00088##

(143) In some embodiments, R.sub.4 is

(144) ##STR00089##

(145) In certain embodiments, R.sub.4 is

(146) ##STR00090##

(147) In certain embodiments, R.sub.4 is

(148) ##STR00091##

(149) In certain embodiments, R.sub.4 is

(150) ##STR00092##

(151) In certain embodiments, R.sub.4 is

(152) ##STR00093##

(153) In certain embodiments, R.sub.4 is

(154) ##STR00094##

(155) In certain embodiments, R.sub.4 is C.sub.1-5 alkyl substituted with 1-4 F, Cl, Br, OH, and C.sub.3-6 cycloalkyl.

(156) In certain embodiments, R.sub.4 is R.sub.4 is selected from

(157) ##STR00095##

(158) As defined above and described herein, R.sub.5 is H, F, Cl, Br, CN, C.sub.1-4alkyl substituted with 0-5 R.sub.e, C.sub.2-4alkenyl, C.sub.2-4alkynyl, nitro, —S(O).sub.pR.sub.c, —S(O).sub.pNR.sub.aR.sub.a, —NR.sub.aS(O).sub.pR.sub.c, —(CH.sub.2).sub.rOR.sub.b, —(CH.sub.2).sub.rNR.sub.aR.sub.a, —NR.sub.aC(═O)R.sub.b, NR.sub.aC(═O)OR.sub.b—NR.sub.aC(═O)NR.sub.aR.sub.a, —C(═O)R.sub.b, —C(═O)OR.sub.b, C(═O)NR.sub.aR.sub.a, —OC(═O)R.sub.b, C.sub.3-6cycloalkyl substituted with 0-4 R.sub.e, aryl substituted with 0-4 R.sub.e, and heterocyclyl substituted with 0-4 R.sub.e.

(159) In some embodiments, R.sub.5 is H, F, Cl, CN, C.sub.1-4alkyl, C.sub.1-4alkyl (substituted with OH, NH.sub.2, and COOH), SC.sub.1-4alkyl, S(O).sub.2C.sub.1-4alkyl, S(O).sub.2NH-cyclopropyl, —(CH.sub.2).sub.0-1NHS(O).sub.2C.sub.1-4alkyl, N(R.sub.d)S(O).sub.2C.sub.2-4alkenyl, —(CH.sub.2).sub.0-1H, OC.sub.1-4alkyl, —(CH.sub.2).sub.0-1NH.sub.2, —(CH.sub.2).sub.0-1NHC(═O)C.sub.1-4alkyl, —NR.sub.dC(═O)C.sub.2-4alkenyl, —NHC(═O)C.sub.2-4alkynyl, —(CH.sub.2).sub.0-1C(═O)OH, —C(═O)OC.sub.1-4alkyl, —NHC(═O)OC.sub.1-4alkyl, —NHC(═O)O(CH.sub.2).sub.2OC.sub.1-4alkyl, —NHC(═O)OCH.sub.2-cyclopropyl, —NHC(═O)NH.sub.2, C(═O)NHC.sub.1-4alkyl, CONH(CH.sub.2).sub.1-2C(═O)OH, —(CH.sub.2).sub.0-1C(═O)NH.sub.2, —(CH.sub.2).sub.0-1C(═O)NHC.sub.1-4alkyl, C(═O)NH-pyridine, —C(═O)NH(CH.sub.2).sub.2N(C.sub.1-4alkyl).sub.2, —C(═O)NH(CH.sub.2).sub.2OH, —C(═O)NH(CH.sub.2).sub.2S(O).sub.2C.sub.1-4alkyl, and —OC(═O)C.sub.1-4alkyl.

(160) In some embodiments, R.sub.5 is

(161) ##STR00096##
In some embodiments, R.sub.5 is

(162) ##STR00097##

(163) In some embodiments, R.sub.5 is F. In some embodiments, R.sub.5 is C.sub.1-4alkyl. In some embodiments, R.sub.5 is —OH or —OC.sub.1-3alkyl. In some embodiments, R.sub.5 is —NHS(O).sub.2C.sub.2-4alkenyl. In certain embodiments, R.sub.5 is selected from those functional groups depicted in the examples below.

(164) As defined above and described herein, R.sub.6 is H, C.sub.1-3alkyl substituted with 0-4 R.sub.e, —S(O).sub.pR.sub.c, —C(═O)R.sub.b, —(CH.sub.2).sub.rC(═O)NR.sub.aR.sub.a, —C(═O)(CH.sub.2).sub.rNR.sub.aC(═O)R.sub.b, —C(═O)OR.sub.b, —S(O).sub.pNR.sub.aR.sub.a, aryl substituted with 0-4 R.sub.e, or heterocyclyl substituted with 0-4 R.sub.e.

(165) In some embodiments, R.sub.6 is H. In some embodiments, R.sub.6 is methyl or isopropyl. In some embodiments, R.sub.6 is —(CH.sub.2).sub.2C(═O)NH.sub.2. In some embodiments, R.sub.6 is —(CH.sub.2).sub.2OH. In some embodiments, R.sub.6 is C(═O)C.sub.1-4alkyl. In certain embodiments, R.sub.6 is selected from those functional groups depicted in the examples below.

(166) As defined above and described herein, R.sub.7 is H, F, Cl, C.sub.1-3alkyl, —NR.sub.aR.sub.a, or —NR.sub.aC(═O)OR.sub.b. In some embodiments, R.sub.7 is NH.sub.2. In some embodiments, R.sub.7 is F.

(167) As defined above and described herein, R.sub.8 is H, F, Cl, Br, or C.sub.1-4alkyl substituted with 0-5 R.sub.c. In some embodiments, R.sub.8 is H. In some embodiments, R.sub.8 is C.sub.1-3alkyl.

(168) As defined above, Ring A is

(169) ##STR00098##

(170) In some embodiments, Ring A is

(171) ##STR00099##
In some embodiments, Ring A is

(172) ##STR00100##
In some embodiments, Ring A is

(173) ##STR00101##
In some embodiments, Ring A is

(174) ##STR00102##
In some embodiments, Ring A is

(175) ##STR00103##
In some embodiments, Ring A is

(176) ##STR00104##
In some embodiments, Ring A is

(177) ##STR00105##

(178) In some embodiments, Ring A is

(179) ##STR00106##
In some embodiments, Ring A is

(180) ##STR00107##
In some embodiments, Ring A is

(181) ##STR00108##
In some embodiments, Ring A is

(182) ##STR00109##
In some embodiments, Ring A is

(183) ##STR00110##
In some embodiments, Ring A is

(184) ##STR00111##
In some embodiments, Ring A is

(185) ##STR00112##
In some embodiments, Ring A is

(186) ##STR00113##
In some embodiments, Ring A is

(187) ##STR00114##
In some embodiments, Ring A is

(188) ##STR00115##
In some embodiments, Ring A is

(189) ##STR00116##
In some embodiments, Ring A is

(190) ##STR00117##
In some embodiments, Ring A is

(191) ##STR00118##

(192) In some embodiments, Ring A is

(193) ##STR00119##
In some embodiments, Ring A is

(194) ##STR00120##
In some embodiments, Ring A is

(195) ##STR00121##
In some embodiments, Ring A is

(196) ##STR00122##
In some embodiments, Ring A is

(197) ##STR00123##
In some embodiments, Ring A is

(198) ##STR00124##
In some embodiments, Ring A is

(199) ##STR00125##
In some embodiments, Ring A is

(200) ##STR00126##
In some embodiments, Ring A is

(201) ##STR00127##
In some embodiments, Ring A is

(202) ##STR00128##
In some embodiments, Ring A is

(203) ##STR00129##

(204) In some embodiments, Ring A is

(205) ##STR00130##
In some embodiments, Ring A is

(206) ##STR00131##
In some embodiments, Ring A is

(207) ##STR00132##
In some embodiments, Ring A is

(208) ##STR00133##
In some embodiments, Ring A is

(209) ##STR00134##
In some embodiments, Ring A is

(210) ##STR00135##
In some embodiments, Ring A is

(211) ##STR00136##
In some embodiments, Ring A is

(212) ##STR00137##
In some embodiments, Ring A is

(213) ##STR00138##
In some embodiments, Ring A is

(214) ##STR00139##

(215) In some embodiments, Ring A is

(216) ##STR00140##
In some embodiments, Ring A is

(217) ##STR00141##
In some embodiments, Ring A is

(218) ##STR00142##
In some embodiments, Ring A is

(219) ##STR00143##
In some embodiments, Ring A is

(220) ##STR00144##
In some embodiments, Ring A is

(221) ##STR00145##
In some embodiments, Ring A is

(222) ##STR00146##
In some embodiments, Ring A is

(223) ##STR00147##
In some embodiments, Ring A is

(224) ##STR00148##

(225) In some embodiments, Ring A is

(226) ##STR00149##
In some embodiments, Ring A is

(227) ##STR00150##
In some embodiments, Ring A is

(228) ##STR00151##
In some embodiments, Ring A is

(229) ##STR00152##
In some embodiments, Ring A is

(230) ##STR00153##
In some embodiments, Ring A is

(231) ##STR00154##
In some embodiments, Ring A is

(232) ##STR00155##
In some embodiments, Ring A is

(233) ##STR00156##
In some embodiments, Ring A is

(234) ##STR00157##

(235) In some embodiments, Ring A is

(236) ##STR00158##
In some embodiments, Ring A is

(237) ##STR00159##
In some embodiments, Ring A is

(238) ##STR00160##
In some embodiments, Ring A is

(239) ##STR00161##
In some embodiments, Ring A is

(240) ##STR00162##
In some embodiments, Ring A is

(241) ##STR00163##
In some embodiments, Ring A is

(242) ##STR00164##
In certain embodiments, R.sub.4 is selected from those functional groups depicted in the examples below.

(243) As defined above and described herein, r is 0-4. In some embodiments, r is 0. In some embodiments, r is 1. In some embodiments, r is 2. In some embodiments, r is 3. In some embodiments, r is 4. In some embodiments, Ring A is

(244) ##STR00165##
R.sub.1 is CH.sub.3, R.sub.2 is cyclopropylmethyl, Q is N or CH, R.sub.3 is H, F, or —OCH.sub.3, R.sub.4 is

(245) ##STR00166##
and R.sub.5 is H, F, Cl, CN, C.sub.1-4alkyl, C.sub.1-4alkyl substituted with OH, NH.sub.2, and COOH, SC.sub.1-4alkyl, S(O).sub.2C.sub.1-4alkyl, S(O).sub.2NH-cyclopropyl, —(CH.sub.2).sub.0-1NHS(O).sub.2C.sub.1-4alkyl, N(R.sub.d)S(O).sub.2C.sub.2-4alkenyl, —(CH.sub.2).sub.0-1OH, OC.sub.1-4alkyl, —(CH.sub.2).sub.0-1NH.sub.2, —(CH.sub.2).sub.0-1NHC(═O)C.sub.1-4alkyl, —NR.sub.dC(═O)C.sub.2-4alkenyl, —NHC(═O)C.sub.2-4alkynyl, —(CH.sub.2).sub.0-1C(═O)OH, —C(═O)OC.sub.1-4alkyl, —NHC(═O)OC.sub.1-4alkyl, —NHC(═O)O(CH.sub.2).sub.2OC.sub.1-4alkyl, —NHC(═O)OCH.sub.2-cyclopropyl, —NHC(═O)NH.sub.2, C(═O)NHC.sub.1-4alkyl, CONH(CH.sub.2).sub.1-2C(═O)OH, —(CH.sub.2).sub.0-1C(═O)NH.sub.2, —(CH.sub.2).sub.0-1C(═O)NHC.sub.1-4alkyl, C(═O)NH-pyridine, —C(═O)NH(CH.sub.2).sub.2N(C.sub.1-4alkyl).sub.2, —C(═O)NH(CH.sub.2).sub.2OH, —C(═O)NH(CH.sub.2).sub.2S(O).sub.2C.sub.1-4alkyl, and —OC(═O)C.sub.1-4alkyl,

(246) ##STR00167##

(247) In some embodiments, Ring A is

(248) ##STR00168##
R.sub.1 is CH.sub.3, R.sub.2 is cyclopropylmethyl, Q is N or CH, R.sub.3 is H, F, or —OCH.sub.3, R.sub.5 is

(249) ##STR00169##
and R.sub.5 is H, F, Cl, CN, C.sub.1-4alkyl, C.sub.1-4alkyl substituted with OH, NH.sub.2, and COOH, SC.sub.1-4alkyl, S(O).sub.2C.sub.1-4alkyl, S(O).sub.2NH-cyclopropyl, —(CH.sub.2).sub.0-1NHS(O).sub.2C.sub.1-4alkyl, N(R.sub.d)S(O).sub.2C.sub.2-4alkenyl, —(CH.sub.2).sub.0-1OH, OC.sub.1-4alkyl, —(CH.sub.2).sub.0-1NH.sub.2, —(CH.sub.2).sub.0-1NHC(═O)C.sub.1-4alkyl, —NR.sub.dC(═O)C.sub.2-4alkenyl, —NHC(═O)C.sub.2-4alkynyl, —(CH.sub.2).sub.0-1C(═O)OH, —C(═O)OC.sub.1-4alkyl, —NHC(═O)OC.sub.1-4alkyl, —NHC(═O)O(CH.sub.2).sub.2OC.sub.1-4alkyl, —NHC(═O)OCH.sub.2-cyclopropyl, —NHC(═O)NH.sub.2, C(═O)NHC.sub.1-4alkyl, CONH(CH.sub.2).sub.1-2C(═O)OH, —(CH.sub.2).sub.0-1C(═O)NH.sub.2, —(CH.sub.2).sub.0-1C(═O)NHC.sub.1-4alkyl, C(═O)NH-pyridine, —C(═O)NH(CH.sub.2).sub.2N(C.sub.1-4alkyl).sub.2, —C(═O)NH(CH.sub.2).sub.2OH, —C(═O)NH(CH.sub.2).sub.2S(O).sub.2C.sub.1-4alkyl, and —OC(═O)C.sub.1-4alkyl,

(250) ##STR00170##

(251) In some embodiments, Ring A is

(252) ##STR00171##
R.sub.1 is CH.sub.3, R2 is cyclopropylmethyl, Q is N or CH, R3 is H, F, or —OCH3, R4 is

(253) ##STR00172##

(254) In some embodiments, Ring A is

(255) ##STR00173##
R.sub.1 is CH.sub.3, R.sub.2 is cyclopropylmethyl, Q is N or CH, R.sub.3 is H, F, or —OCH.sub.3, R.sub.4 is

(256) ##STR00174##

(257) In some embodiments, Ring A is

(258) ##STR00175##
R.sub.1 is CH.sub.3, R.sub.2 is cyclopropylmethyl, Q is N or CH, R.sub.3 is H, F, or —OCH.sub.3, R.sub.4 is

(259) ##STR00176##

(260) In some embodiments, Ring A is

(261) ##STR00177##
R.sub.1 is CH.sub.3, R.sub.2 is cyclopropylmethyl, Q is N or CH, R.sub.3 is H, F, or —OCH.sub.3, R.sub.4 is

(262) ##STR00178##

(263) In some embodiments, Ring A is or

(264) ##STR00179##
R.sub.1 is CH.sub.3, R.sub.2 is cyclopropylmethyl, Q is N or CH, R.sub.3 is H, F, or —OCH.sub.3, R.sub.4 is

(265) ##STR00180##

(266) In some embodiments, Ring A is

(267) ##STR00181##
R.sub.1 is CH.sub.3, R.sub.2 is cyclopropylmethyl, Q is N or CH, R.sub.3 is H, F, or —OCH.sub.3, R.sub.4 is

(268) ##STR00182## ##STR00183##

(269) In some embodiments, Ring A is

(270) ##STR00184##
R.sub.1 is CH.sub.3, R.sub.2 is cyclopropylmethyl, Q is N or CH, R.sub.3 is H, F, or —OCH.sub.3, R.sub.4 is

(271) ##STR00185##
and R.sub.5 is H, F, C.sub.1-4alkyl, —OH, —OC.sub.1-3alkyl and —NHS(O).sub.2C.sub.2-4alkenyl.

(272) In some embodiments, the compound of formula (I) is selected from examples depicted below. In certain embodiments, the present invention provides any compound described above and herein, or a pharmaceutically acceptable salt thereof or a composition for use in therapy. In some embodiments, the present invention provides any compound described above and herein in isolated form. In some embodiments, the present invention provides the compounds according to any one of claims 1 to 16

4. Uses, Formulation and Administration

(273) Pharmaceutically Acceptable Compositions

(274) According to another embodiment, the invention provides a composition comprising a compound of this invention or a pharmaceutically acceptable derivative thereof and a pharmaceutically acceptable carrier, adjuvant, or vehicle. The amount of compound in compositions of this invention is such that is effective to measurably inhibit PAD4, in a biological sample or in a patient. In certain embodiments, the amount of compound in compositions of this invention is such that is effective to measurably inhibit PAD4, in a biological sample or in a patient. In certain embodiments, a composition of this invention is formulated for administration to a patient in need of such composition. In some embodiments, a composition of this invention is formulated for oral administration to a patient.

(275) The term “subject,” as used herein, is used interchangeably with the term “patient” and means an animal, preferably a mammal. In some embodiments, a subject or patient is a human. In other embodiments, a subject (or patient) is a veterinary subject (or patient). In some embodiments, a veterinary subject (or patient) is a canine, a feline, or an equine subject.

(276) The term “pharmaceutically acceptable carrier, adjuvant, or vehicle” refers to a non-toxic carrier, adjuvant, or vehicle that does not destroy the pharmacological activity of the compound with which it is formulated. Pharmaceutically acceptable carriers, adjuvants or vehicles that may be used in the compositions of this invention include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, serum proteins, such as human serum albumin, buffer substances such as phosphates, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts or electrolytes, such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinyl pyrrolidone, cellulose-based substances, polyethylene glycol, sodium carboxymethylcellulose, polyacrylates, waxes, polyethylene-polyoxypropylene-block polymers, polyethylene glycol and wool fat.

(277) Compositions of the present invention may be administered orally, parenterally, by inhalation spray, topically, rectally, nasally, buccally, vaginally or via an implanted reservoir. The term “parenteral” as used herein includes subcutaneous, intravenous, intramuscular, intra-articular, intra-synovial, intrasternal, intrathecal, intrahepatic, intralesional and intracranial injection or infusion techniques. Preferably, the compositions are administered orally, intraperitoneally or intravenously. Sterile injectable forms of the compositions of this invention may be aqueous or oleaginous suspension. These suspensions may be formulated according to techniques known in the art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent, for example as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium.

(278) For this purpose, any bland fixed oil may be employed including synthetic mono- or di-glycerides. Fatty acids, such as oleic acid and its glyceride derivatives are useful in the preparation of injectables, as are natural pharmaceutically-acceptable oils, such as olive oil or castor oil, especially in their polyoxyethylated versions. These oil solutions or suspensions may also contain a long-chain alcohol diluent or dispersant, such as carboxymethyl cellulose or similar dispersing agents that are commonly used in the formulation of pharmaceutically acceptable dosage forms including emulsions and suspensions. Other commonly used surfactants, such as Tweens, Spans and other emulsifying agents or bioavailability enhancers which are commonly used in the manufacture of pharmaceutically acceptable solid, liquid, or other dosage forms may also be used for the purposes of formulation.

(279) Pharmaceutically acceptable compositions of this invention may be orally administered in any orally acceptable dosage form including, but not limited to, capsules, tablets, aqueous suspensions or solutions. In the case of tablets for oral use, carriers commonly used include lactose and corn starch. Lubricating agents, such as magnesium stearate, are also typically added. For oral administration in a capsule form, useful diluents include lactose and dried cornstarch. When aqueous suspensions are required for oral use, the active ingredient is combined with emulsifying and suspending agents. If desired, certain sweetening, flavoring or coloring agents may also be added.

(280) Alternatively, pharmaceutically acceptable compositions of this invention may be administered in the form of suppositories for rectal administration. These can be prepared by mixing the agent with a suitable non-irritating excipient that is solid at room temperature but liquid at rectal temperature and therefore will melt in the rectum to release the drug. Such materials include cocoa butter, beeswax and polyethylene glycols.

(281) Pharmaceutically acceptable compositions of this invention may also be administered topically, especially when the target of treatment includes areas or organs readily accessible by topical application, including diseases of the eye, the skin, or the lower intestinal tract. Suitable topical formulations are readily prepared for each of these areas or organs.

(282) Topical application for the lower intestinal tract can be effected in a rectal suppository formulation (see above) or in a suitable enema formulation. Topically-transdermal patches may also be used.

(283) For topical applications, provided pharmaceutically acceptable compositions may be formulated in a suitable ointment containing the active component suspended or dissolved in one or more carriers. Carriers for topical administration of compounds of this invention include, but are not limited to, mineral oil, liquid petrolatum, white petrolatum, propylene glycol, polyoxyethylene, polyoxypropylene compound, emulsifying wax and water. Alternatively, provided pharmaceutically acceptable compositions can be formulated in a suitable lotion or cream containing the active components suspended or dissolved in one or more pharmaceutically acceptable carriers. Suitable carriers include, but are not limited to, mineral oil, sorbitan monostearate, polysorbate 60, cetyl esters wax, cetearyl alcohol, 2-octyldodecanol, benzyl alcohol and water.

(284) For ophthalmic use, provided pharmaceutically acceptable compositions may be formulated as micronized suspensions in isotonic, pH adjusted sterile saline, or, preferably, as solutions in isotonic, pH adjusted sterile saline, either with or without a preservative such as benzylalkonium chloride. Alternatively, for ophthalmic uses, the pharmaceutically acceptable compositions may be formulated in an ointment such as petrolatum.

(285) Pharmaceutically acceptable compositions of this invention may also be administered by nasal aerosol or inhalation. Such compositions are prepared according to techniques well-known in the art of pharmaceutical formulation and may be prepared as solutions in saline, employing benzyl alcohol or other suitable preservatives, absorption promoters to enhance bioavailability, fluorocarbons, and/or other conventional solubilizing or dispersing agents.

(286) Most preferably, pharmaceutically acceptable compositions of this invention are formulated for oral administration. Such formulations may be administered with or without food. In some embodiments, pharmaceutically acceptable compositions of this invention are administered without food. In other embodiments, pharmaceutically acceptable compositions of this invention are administered with food.

(287) Pharmaceutically acceptable compositions of this invention can be administered to humans and other animals orally, rectally, parenterally, intracisternally, intravaginally, intraperitoneally, topically (as by powders, ointments, or drops), bucally, as an oral or nasal spray, or the like, depending on the severity of the infection being treated. In certain embodiments, the compounds of the invention may be administered orally or parenterally at dosage levels of about 0.01 mg/kg to about 50 mg/kg and preferably from about 1 mg/kg to about 25 mg/kg, of subject body weight per day, one or more times a day, to obtain the desired therapeutic effect.

(288) Liquid dosage forms for oral administration include, but are not limited to, pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active compounds, the liquid dosage forms may contain inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. Besides inert diluents, the oral compositions can also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents.

(289) Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions may be formulated according to the known art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution, suspension or emulsion in a nontoxic parenterally acceptable diluent or solvent, for example, as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution, U.S.P. and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil can be employed including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid are used in the preparation of injectables.

(290) Injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable medium prior to use.

(291) In order to prolong the effect of a compound of the present invention, it is often desirable to slow the absorption of the compound from subcutaneous or intramuscular injection. This may be accomplished by the use of a liquid suspension of crystalline or amorphous material with poor water solubility. The rate of absorption of the compound then depends upon its rate of dissolution that, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of a parenterally administered compound form is accomplished by dissolving or suspending the compound in an oil vehicle. Injectable depot forms are made by forming microencapsule matrices of the compound in biodegradable polymers such as polylactide-polyglycolide. Depending upon the ratio of compound to polymer and the nature of the particular polymer employed, the rate of compound release can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Depot injectable formulations are also prepared by entrapping the compound in liposomes or microemulsions that are compatible with body tissues.

(292) Compositions for rectal or vaginal administration are preferably suppositories which can be prepared by mixing the compounds of this invention with suitable non-irritating excipients or carriers such as cocoa butter, polyethylene glycol or a suppository wax which are solid at ambient temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active compound.

(293) Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active compound is mixed with at least one inert, pharmaceutically acceptable excipient or carrier such as sodium citrate or dicalcium phosphate and/or a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol, and silicic acid, b) binders such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidinone, sucrose, and acacia, c) humectants such as glycerol, d) disintegrating agents such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate, e) solution retarding agents such as paraffin, f) absorption accelerators such as quaternary ammonium compounds, g) wetting agents such as, for example, cetyl alcohol and glycerol monostearate, h) absorbents such as kaolin and bentonite clay, and i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. In the case of capsules, tablets and pills, the dosage form may also comprise buffering agents.

(294) Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like. The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings and other coatings well known in the pharmaceutical formulating art. They may optionally contain opacifying agents and can also be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions that can be used include polymeric substances and waxes. Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polethylene glycols and the like.

(295) The active compounds can also be in micro-encapsulated form with one or more excipients as noted above. The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings, release controlling coatings and other coatings well known in the pharmaceutical formulating art. In such solid dosage forms the active compound may be admixed with at least one inert diluent such as sucrose, lactose or starch. Such dosage forms may also comprise, as is normal practice, additional substances other than inert diluents, e.g., tableting lubricants and other tableting aids such a magnesium stearate and microcrystalline cellulose. In the case of capsules, tablets and pills, the dosage forms may also comprise buffering agents. They may optionally contain opacifying agents and can also be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions that can be used include polymeric substances and waxes.

(296) Dosage forms for topical or transdermal administration of a compound of this invention include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants or patches. The active component is admixed under sterile conditions with a pharmaceutically acceptable carrier and any needed preservatives or buffers as may be required. Ophthalmic formulation, ear drops, and eye drops are also contemplated as being within the scope of this invention. Additionally, the present invention contemplates the use of transdermal patches, which have the added advantage of providing controlled delivery of a compound to the body. Such dosage forms can be made by dissolving or dispensing the compound in the proper medium. Absorption enhancers can also be used to increase the flux of the compound across the skin. The rate can be controlled by either providing a rate controlling membrane or by dispersing the compound in a polymer matrix or gel.

(297) The amount of compounds of the present invention that may be combined with the carrier materials to produce a composition in a single dosage form will vary depending upon the host treated, the particular mode of administration. Preferably, provided compositions should be formulated so that a dosage of between 0.01-100 mg/kg body weight/day of the inhibitor can be administered to a patient receiving these compositions.

(298) A compound of the current invention can be administered alone or in combination with one or more other therapeutic compounds, possible combination therapy taking the form of fixed combinations or the administration of a compound of the invention and one or more other therapeutic compounds being staggered or given independently of one another, or the combined administration of fixed combinations and one or more other therapeutic compounds. Exemplary of such other therapeutic agents include corticosteroids, rolipram, calphostin, cytokine-suppressive anti-inflammatory drugs (CSAIDs), Interleukin-10, glucocorticoids, salicylates, nitric oxide, and other immunosuppressants; nuclear translocation inhibitors, such as deoxyspergualin (DSG); non-steroidal antiinflammatory drugs (NSAIDs) such as ibuprofen, celecoxib and rofecoxib; steroids such as prednisone or dexamethasone; antiviral agents such as abacavir; antiproliferative agents such as methotrexate, leflunomide, FK506 (tacrolimus, Prograf); cytotoxic drugs such as azathiprine and cyclophosphamide; TNF-α inhibitors such as tenidap, anti-TNF antibodies or soluble TNF receptor, and rapamycin (sirolimus or Rapamune) or derivatives thereof. A compound of the current invention can besides or in addition be administered especially for tumor therapy in combination with chemotherapy, radiotherapy, immunotherapy, phototherapy, surgical intervention, or a combination of these. Long-term therapy is equally possible as is adjuvant therapy in the context of other treatment strategies, as described above. Other possible treatments are therapy to maintain the patient's status after tumor regression, or even chemopreventive therapy, for example in patients at risk.

(299) Those additional agents may be administered separately from an inventive compound-containing composition, as part of a multiple dosage regimen. Alternatively, those agents may be part of a single dosage form, mixed together with a compound of this invention in a single composition. If administered as part of a multiple dosage regime, the two active agents may be submitted simultaneously, sequentially or within a period of time from one another normally within five hours from one another.

(300) As used herein, the term “combination,” “combined,” and related terms refers to the simultaneous or sequential administration of therapeutic agents in accordance with this invention. For example, a compound of the present invention may be administered with another therapeutic agent simultaneously or sequentially in separate unit dosage forms or together in a single unit dosage form. Accordingly, the present invention provides a single unit dosage form comprising a compound of the current invention, an additional therapeutic agent, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

(301) The amount of both an inventive compound and additional therapeutic agent (in those compositions which comprise an additional therapeutic agent as described above) that may be combined with the carrier materials to produce a single dosage form will vary depending upon the host treated and the particular mode of administration. Preferably, compositions of this invention should be formulated so that a dosage of between 0.01-100 mg/kg body weight/day of an inventive compound can be administered.

(302) In those compositions which comprise an additional therapeutic agent, that additional therapeutic agent and the compound of this invention may act synergistically. Therefore, the amount of additional therapeutic agent in such compositions will be less than that required in a monotherapy utilizing only that therapeutic agent.

(303) The amount of additional therapeutic agent present in the compositions of this invention will be no more than the amount that would normally be administered in a composition comprising that therapeutic agent as the only active agent. Preferably the amount of additional therapeutic agent in the presently disclosed compositions will range from about 50% to 100% of the amount normally present in a composition comprising that agent as the only therapeutically active agent.

(304) It should also be understood that a specific dosage and treatment regimen for any particular patient will depend upon a variety of factors, including the activity of the specific compound employed, the age, body weight, general health, sex, diet, time of administration, rate of excretion, drug combination, and the judgment of the treating physician and the severity of the particular disease being treated. The amount of a compound of the present invention in the composition will also depend upon the particular compound in the composition.

5. Uses of Compounds and Pharmaceutically Acceptable Compositions

(305) Compounds and compositions described herein are generally useful for the inhibition of PAD4.

(306) The activity of a compound utilized in this invention as an inhibitor of PAD4, may be assayed in vitro, in vivo or in a cell line. In vitro assays include assays that determine the inhibition of PAD4. Detailed conditions for assaying a compound utilized in this invention as an inhibitor of PAD4 are set forth in the Examples below. In some embodiments, a provided compound inhibits PAD4 selectively as compared to PAD2.

(307) As used herein, the terms “treatment,” “treat,” and “treating” refer to reversing, alleviating, delaying the onset of, or inhibiting the progress of a disease or disorder, or one or more symptoms thereof, as described herein. In some embodiments, treatment may be administered after one or more symptoms have developed. In other embodiments, treatment may be administered in the absence of symptoms. For example, treatment may be administered to a susceptible individual prior to the onset of symptoms (e.g., in light of a history of symptoms and/or in light of genetic or other susceptibility factors). Treatment may also be continued after symptoms have resolved, for example to prevent or delay their recurrence.

(308) Provided compounds are inhibitors of PAD4 and are therefore useful for treating one or more disorders associated with activity of PAD4. Thus, in certain embodiments, the present invention provides a method for treating a PAD4-mediated disorder comprising the step of administering to a patient in need thereof a compound of the present invention, or pharmaceutically acceptable composition thereof.

(309) In one embodiment, a PAD4-mediated disorder is a disease, condition, or disorder mediated by inappropriate PAD4 activity. In some embodiments, a PAD4-mediated disorder is selected from the group consisting of rheumatoid arthritis, vasculitis, systemic lupus erythematosus, ulcerative colitis, cancer, cystic fibrosis, asthma, cutaneous lupus erythematosus, and psoriasis. In a further embodiment, the disorder mediated by inappropriate PAD4 activity is rheumatoid arthritis. In a further embodiment, the disorder mediated by inappropriate PAD4 activity is systemic lupus. In a further embodiment, the disorder mediated by inappropriate PAD4 activity is vasculitis. In a further embodiment, the disorder mediated by inappropriate PAD4 activity is cutaneous lupus erythematosus. In a further embodiment, the disorder mediated by inappropriate PAD4 activity is psoriasis.

(310) In one embodiment there is provided a method of treatment of rheumatoid arthritis, vasculitis, systemic lupus erythematosus, ulcerative colitis, cancer, cystic fibrosis, asthma, cutaneous lupus erythematosus, or psoriasis, which method comprises administering to a human subject in need thereof, a therapeutically effective amount of a provided compound or a pharmaceutically acceptable salt thereof.

(311) In one embodiment there is provided a method of treatment of rheumatoid arthritis, which method comprises administering to a human subject in need thereof, a therapeutically effective amount of a provided compound, or a pharmaceutically acceptable salt thereof. In one embodiment there is provided a method of treatment of systemic lupus, which method comprises administering to a human subject in need thereof, a therapeutically effective amount of a provided compound, or a pharmaceutically acceptable salt thereof. In one embodiment there is provided a method of treatment of vasculitis, which method comprises administering to a human subject in need thereof, a therapeutically effective amount of a provided compound, or a pharmaceutically acceptable salt thereof. In one embodiment there is provided a method of treatment of cutaneous lupus erythematosus, which method comprises administering to a human subject in need thereof, a therapeutically effective amount of a provided compound, or a pharmaceutically acceptable salt thereof. In one embodiment there is provided a method of treatment of psoriasis, which method comprises administering to a human subject in need thereof, a therapeutically effective amount of a provided compound, or a pharmaceutically acceptable salt thereof.

(312) In some embodiments, a PAD4-mediated disorder is selected from the group consisting of acid-induced lung injury, acne (PAPA), acute lymphocytic leukemia, acute, respiratory distress syndrome, Addison's disease, adrenal hyperplasia, adrenocortical insufficiency, ageing, AIDS, alcoholic hepatitis, alcoholic hepatitis, alcoholic liver disease, allergen induced asthma, allergic bronchopulmonary, aspergillosis, allergic conjunctivitis, alopecia, Alzheimer's disease, amyloidosis, amyotropic lateral sclerosis, and weight loss, angina pectoris, angioedema, anhidrotic ecodermal dysplasia-ID, ankylosing spondylitis, anterior segment, inflammation, antiphospholipid syndrome, aphthous stomatitis, appendicitis, arthritis, asthma, atherosclerosis, atopic dermatitis, autoimmune diseases, autoimmune hepatitis, bee sting-induced inflammation, Bechet's disease, Bechet's syndrome, Bells Palsey, berylliosis, Blau syndrome, bone pain, bronchiolitis, burns, bursitis, cancer, cardiac hypertrophy, carpal tunnel syndrome, catabolic disorders, cataracts, cerebral aneurysm, chemical irritant-induced inflammation, chorioretinitis, chronic heart failure, chronic lung disease of prematurity, chronic lymphocytic leukemia, chronic obstructive pulmonary disease, colitis, complex regional pain syndrome, connective tissue disease, corneal ulcer, crohn's disease, cryopyrin-associated periodic syndromes, cyrptococcosis, cystic fibrosis, deficiency of the interleukin-1-receptor antagonist (DIRA), dermatitis, dermatitis endotoxemia, dermatomyositis, diffuse intrinsic pontine glioma, endometriosis, endotoxemia, epicondylitis, erythroblastopenia, familial amyloidotic polyneuropathy, familial cold urticarial, familial Mediterranean fever, fetal growth retardation, glaucoma, glomerular disease, glomerular nephritis, gout, gouty arthritis, graft-versus-host disease, gut diseases, head injury, headache, hearing loss, heart disease, hemolytic anemia, Henoch-Scholein purpura, hepatitis, hereditary periodic fever syndrome, herpes zoster and simplex, HIV-1, Hodgkin's disease, Huntington's disease, hyaline membrane disease, hyperammonemia, hypercalcemia, hypercholesterolemia, hyperimmunoglobulinemia D with recurrent fever (HIDS), hypoplastic and other anemias, hypoplastic anemia, idiopathic thrombocytopenic purpura, incontinentia pigmenti, infectious mononucleosis, inflammatory bowel disease, inflammatory lung disease, inflammatory neuropathy, inflammatory pain, insect bite-induced inflammation, iritis, irritant-induced inflammation, ischemia/reperfusion, juvenile rheumatoid arthritis, keratitis, kidney disease, kidney injury caused by parasitic infections, kidney injury caused by parasitic infections, kidney transplant rejection prophylaxis, leptospiriosis, leukemia, Loeffler's syndrome, lung injury, lung injury, lupus, lupus, lupus nephritis, lymphoma, meningitis, mesothelioma, mixed connective tissue disease, Muckle-Wells syndrome (urticaria deafness amyloidosis), multiple sclerosis, muscle wasting, muscular dystrophy, myasthenia gravis, myocarditis, mycosis fungiodes, mycosis fungoides, myelodysplastic syndrome, myositis, nasal sinusitis, necrotizing enterocolitis, neonatal onset multisystem inflammatory disease (NOMID), nephrotic syndrome, neuritis, neuropathological diseases, non-allergen induced asthma, obesity, ocular allergy, optic neuritis, organ transplant, osteoarthritis, otitis media, Paget's disease, pain, pancreatitis, Parkinson's disease, pemphigus, pericarditis, periodic fever, periodontitis, peritoneal endometriosis, pertussis, pharyngitis and adenitis (PFAPA syndrome), plant irritant-induced inflammation, pneumonia, pneumonitis, pneumosysts infection, poison ivy/urushiol oil-induced inflammation, polyarteritis nodosa, polychondritis, polycystic kidney disease, polymyositis, psoriasis, psoriasis, psoriasis, psoriasis, psychosocial stress diseases, pulmonary disease, pulmonary hypertension, pulmonayr fibrosis, pyoderma gangrenosum, pyogenic sterile arthritis, renal disease, retinal disease, rheumatic carditis, rheumatic disease, rheumatoid arthritis, sarcoidosis, seborrhea, sepsis, severe pain, sickle cell, sickle cell anemia, silica-induced disease, Sjogren's syndrome, skin diseases, sleep apnea, solid tumors, spinal cord injury, Stevens-Johnson syndrome, stroke, subarachnoid hemorrhage, sunburn, temporal arteritis, tenosynovitis, thrombocytopenia, thyroiditis, tissue transplant, TNF receptor associated periodic syndrome (TRAPS), toxoplasmosis, transplant, traumatic brain injury, tuberculosis, type 1 diabetes, type 2 diabetes, ulcerative colitis, urticarial, uveitis, Wegener's granulomatosis, interstitial lung disease, psoriatic arthritis, juvenile idiopathic arthritis, Sjogren's syndrome, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, antiphospholipid antibody syndrome, sepsis, deep vein thrombosis, fibrosis, Alzheimer's, scleroderma and CREST syndrome.

(313) In one embodiment, the invention provides a provided compound, or a pharmaceutically acceptable salt thereof, for use in therapy. In another embodiment, the invention provides a provided compound, or a pharmaceutically acceptable salt thereof, for use in the treatment of a disorder mediated by inappropriate PAD4 activity. In another embodiment, the invention provides a provided compound, or a pharmaceutically acceptable salt thereof, for use in the treatment of rheumatoid arthritis, vasculitis, systemic lupus erythematosus, ulcerative colitis, cancer, cystic fibrosis, asthma, cutaneous lupus erythematosus, or psoriasis. In another embodiment, the invention provides a provided compound, or a pharmaceutically acceptable salt thereof, for use in the treatment of rheumatoid arthritis. In another embodiment, the invention provides a provided compound, or a pharmaceutically acceptable salt thereof, for use in the treatment of systemic lupus. In another embodiment, the invention provides a provided compound, or a pharmaceutically acceptable salt thereof, for use in the treatment of vasculitis. In another embodiment, the invention provides a provided compound, or a pharmaceutically acceptable salt thereof, for use in the treatment of cutaneous lupus erythematosus. In another embodiment, the invention provides a provided compound, or a pharmaceutically acceptable salt thereof, for use in the treatment of psoriasis. In another embodiment, the invention provides the use of a provided compound, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in the treatment of a disorder mediated by inappropriate PAD4 activity. In another embodiment, the invention provides the use of a provided compound, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in the treatment of rheumatoid arthritis, vasculitis, systemic lupus erythematosus, ulcerative colitis, cancer, cystic fibrosis, asthma, cutaneous lupus erythematosus, or psoriasis. In another embodiment, the invention provides the use of a provided compound, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in the treatment of rheumatoid arthritis. In another embodiment, the invention provides the use of a provided compound, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in the treatment of systemic lupus. In another embodiment, the invention provides the use of a provided compound, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in the treatment of vasculitis. In another embodiment, the invention provides the use of a provided compound, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in the treatment of cutaneous lupus erythematosus. In another embodiment, the invention provides the use of a provided compound, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in the treatment of psoriasis. In a further embodiment, the invention provides a pharmaceutical composition for the treatment or prophylaxis of a disorder mediated by inappropriate PAD4 activity comprising a provided compound, or a pharmaceutically acceptable salt thereof. In a further embodiment, the invention provides a pharmaceutical composition for the treatment or prophylaxis of rheumatoid arthritis, vasculitis, systemic lupus erythematosus, ulcerative colitis, cancer, cystic fibrosis, asthma, cutaneous lupus erythematosus, or psoriasis, comprising a provided compound, or a pharmaceutically acceptable salt thereof. In a further embodiment, the invention provides a pharmaceutical composition for the treatment or prophylaxis of rheumatoid arthritis comprising a provided compound, or a pharmaceutically acceptable salt thereof. In a further embodiment, the invention provides a pharmaceutical composition for the treatment or prophylaxis of systemic lupus comprising a provided compound, or a pharmaceutically acceptable salt thereof. In a further embodiment, the invention provides a pharmaceutical composition for the treatment or prophylaxis of vasculitis comprising a provided compound, or a pharmaceutically acceptable salt thereof. In a further embodiment, the invention provides a pharmaceutical composition for the treatment or prophylaxis of cutaneous lupus erythematosus comprising a provided compound, or a pharmaceutically acceptable salt thereof. In a further embodiment, the invention provides a pharmaceutical composition for the treatment or prophylaxis of psoriasis comprising a provided compound, or a pharmaceutically acceptable salt thereof

(314) All features of each of the aspects of the invention apply to all other aspects mutatis mutandis.

(315) In order that the invention described herein may be more fully understood, the following examples are set forth. It should be understood that these examples are for illustrative purposes only and are not to be construed as limiting this invention in any manner.

EXEMPLIFICATION

(316) As depicted in the Examples below, in certain exemplary embodiments, compounds are prepared according to the following general procedures. It will be appreciated that, although the general methods depict the synthesis of certain compounds of the present invention, the following general methods, and other methods known to one of ordinary skill in the art, can be applied to all compounds and subclasses and species of each of these compounds, as described herein.

(317) Certain compounds of the present invention were prepared according to Schemes described below.

(318) ##STR00186##
For compounds that involve heteroatom couplings, see Scheme 2.

(319) ##STR00187##
For the synthesis of sulfones, see Scheme 3.

(320) ##STR00188##
For the synthesis of carboxamides, see Scheme 4.

(321) ##STR00189##
For the synthesis of compounds involving photoredox chemistry, see Scheme 5.

(322) ##STR00190##
Description of Analytical LCMS Methods:

(323) Method 1: Column: Waters XBridge C18, 2.1 mm×50 mm, 1.7 μm particles; Mobile Phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate; Temperature: 50° C.; Gradient: 0% B to 100% B over 3 min, then a 0.5 min hold at 100% B; Flow: 1 mL/min; Detection: MS and UV (220 nm).

(324) Method 2: Column: Waters XBridge C18, 2.1 mm×50 mm, 1.7 μm particles; Mobile Phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid; Mobile Phase B: 95:5 acetonitrile:water with 0.1% trifluoroacetic acid; Temperature: 50° C.; Gradient: 0% B to 100% B over 3 min, then a 0.5 min hold at 100% B; Flow: 1 mL/min; Detection: MS and UV (220 nm).

(325) Method 3: Waters Acquity UPLC BEH C18, 2.1×50 mm, 1.7 μm particles; Mobile Phase A: water with 0.05% TFA; Mobile Phase B: ACN with 0.05% TFA; Gradient: 2-98% B over 1 minute, then a 0.5 minute hold at 98% B; Flow: 0.8 mL/min; Detection: UV at 254 nm.

(326) The structures drawn in the current application generically as A below (FIG. 1) are meant as a representation of the fully chiral structure B, with the chiral azabicycloheptane moiety named as ((1R,4R,7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl).

(327) ##STR00191##

Intermediate 1

2-(6-chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylic acid

(328) ##STR00192##

(329) The methyl 2-(6-chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (4 g, 9.41 mmol) [for this starting material see: WO 2017/0100594)] was dissolved in THF (45 mL), MeOH (15 mL) and 2M LiOH aq (9.41 mL). This was stirred at 70° C. for 90 min. To add to this, the reaction was repeated as follows: The methyl 2-(6-chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (2.9 g, 6.83 mmol) was dissolved in THF (24 mL), MeOH (8 mL) and 2M LiOH aq (6.83 ml). The saponification was found to be over as per LCMS. This crude was combined with the earlier reaction crude. The mixture was slowly treated with 2N HCl until the pH reached ˜6. At this stage a tan colored solid precipitated out as 2-(6-chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylic acid (6.9 g): .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 12.83 (br s, 1H), 8.20 (d, J=8.3 Hz, 1H), 7.96 (s, 1H), 7.41 (s, 1H), 7.28 (d, J=8.2 Hz, 1H), 7.17 (s, 1H), 4.44 (br d, J=6.9 Hz, 2H), 4.15 (s, 3H), 4.02 (s, 3H), 1.18-1.04 (m, 1H), 0.36-0.27 (m, 2H), 0.13 (q, J=4.7 Hz, 2H), LCMS (M+H)+=411.3, retention time=1.01 min (Method 3).

Intermediate 2

tert-butyl ((1R,4R,7R)-2-(2-(6-chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carbonyl)-2-azabicyclo[2.2.1]heptan-7-yl)carbamate

(330) ##STR00193##

(331) To a mixture of 5-(6-chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylic acid (5.8 g, 14.12 mmol), tert-butyl ((7R)-2-azabicyclo[2.2.1]heptan-7-yl)carbamate (3.30 g, 15.53 mmol), and Hunig's Base (7.40 ml, 42.4 mmol) was added DMF (35 mL). The mixture became a solid, and therefore, additional DMF (100 ml) was added (became a slurry). Next, this was treated with HATU (6.44 g, 16.94 mmol) in portions to ensure that the HATU was dissolved before adding the next portion. The reaction eventually went into a yellow colored solution. After 2 h of stirring at rt, the reaction was found to be complete. The reaction mixture was diluted with EtOAc and washed with 10% LiCl aq (2×) followed by brine. The combined aq layer was extracted with EtOAc. The combined organic layer was dried (MgSO4), filtered, and concentrated to a dark yellow brown oil. This brown oil was purified by flash chromatography (EtOAc/Hexane), and the product fractions were combined and concentrated to give tert-butyl ((1R,4R,7R)-2-(2-(6-chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carbonyl)-2-azabicyclo[2.2.1]heptan-7-yl)carbamate (11 g): .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 8.19 (d, J=8.2 Hz, 1H), 7.51-7.36 (m, 1H), 7.27 (d, J=8.2 Hz, 1H), 7.13 (s, 1H), 7.01-6.95 (m, 1H), 4.44 (br d, J=7.1 Hz, 2H), 4.12 (s, 3H), 4.00 (s, 3H), 3.74-3.45 (m, 2H), 3.32 (s, 1H), 3.11-3.03 (m, 1H), 2.48-2.37 (m, 1H), 2.00-1.89 (m, 1H), 1.80 (br s, 2H), 1.52-1.44 (m, 1H), 1.44-1.28 (m, 9H), 1.15-1.05 (m, J=4.6 Hz, 1H), 0.30 (br d, J=7.7 Hz, 2H), 0.13 (br d, J=4.8 Hz, 2H), LCMS (M+H)+=605.3, retention time=1.05 min (Method 3).

Intermediate 3

tert-butyl ((1R,4R,7R)-2-(2-(6-chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carbonyl)-2-azabicyclo[2.2.1]heptan-7-yl)carbamate

(332) ##STR00194##

(333) A portion of the above tert-butyl ((1R,4R,7R)-2-(2-(6-chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carbonyl)-2-azabicyclo[2.2.1]heptan-7-yl)carbamate (9 g) was dissolved in DCM (100 mL) and treated with TFA (25 mL). After 2 h, additional TFA (15 mL) was added. After 1 h, the reaction was concentrated and then it was dissolved in EtOAc. It was made basic with a very slow addition of solid NaHCO.sub.3. After the effervescence subsided, it was allowed to stir for 30 min more. The organic layer was separated and washed with brine. Combined aq layer was extracted with EtOAc. Combined organic layer was dried (MgSO4), filtered and concentrated to yield ((1R,4R,7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(6-chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-5-yl)methanone (7 g) as a yellow foamy solid: .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 8.20 (d, J=8.2 Hz, 1H), 7.55-7.39 (m, 1H), 7.28 (d, J=8.2 Hz, 1H), 7.15 (s, 1H), 7.02-6.95 (m, 1H), 4.44 (br d, J=6.9 Hz, 2H), 4.13 (s, 3H), 4.07-4.04 (m, 1H), 4.00 (s, 3H), 3.79-3.40 (m, 2H), 3.19-3.10 (m, 1H), 2.48-2.43 (m, 1H), 1.97-1.81 (m, 3H), 1.62-1.53 (m, 1H), 1.14-1.02 (m, 1H), 0.35-0.28 (m, 2H), 0.12 (br s, 2H); LCMS (M+H)+=505.3, retention time=0.86 min (Method 3).

Example 1

6-(2-(5-((1R,4R,7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-1-methyl-1H-benzo[d]imidazol-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-3,4-dihydroquinolin-2(1H)-one

(334) ##STR00195##

(335) A 2 dr pressure vial was charged with ((1R,4R,7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(6-chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-methyl-1H-benzo[d]imidazol-5-yl)methanone (25 mg, 0.053 mmol), 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroquinolin-2(1H)-one (17.25 mg, 0.063 mmol), 3M potassium phosphate tribasic aq (0.053 mL, 0.158 mmol) and 1,1′-Bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (4.30 mg, 5.26 μmol) in THF (1 mL). The vial was capped and the reaction mixture was made anaerobic by a pump/backfill with nitrogen cycle (5×). The reaction was set to stir at 70° C. for 7 h. The mixture was concentrated and dried in vacuo. It was dissolved in DMF and purified via preparative LC/MS with the following conditions: Column: XBridge C18, 200 mm×19 mm, 5-μm particles; Mobile Phase A: 5:95 acetonitrile:water with 10-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10-mM ammonium acetate; Gradient: a 0-minute hold at 15% B, 15-55% B over 20 minutes, then a 4-minute hold at 100% B; Flow Rate: 20 mL/min; Column Temperature: 25 C. Fraction collection was triggered by MS and UV signals. Fractions containing the desired product were combined and dried via centrifugal evaporation. The purified material was then diluted with DMF, treated with Si-Pyridine and shaken for a minimum of 2 h. The resulting mixture was filtered and dried via centrifugal evaporation to give 6-(2-(5-((1R,4R,7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-1-methyl-1H-benzo[d]imidazol-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-3,4-dihydroquinolin-2(1H)-one (12 mg): .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 10.08 (s, 1H), 8.15 (d, J=8.2 Hz, 1H), 8.02-7.97 (m, 2H), 7.89-7.78 (m, 1H), 7.76-7.69 (m, 2H), 7.45 (br d, J=8.6 Hz, 1H), 7.10 (s, 1H), 7.01 (d, J=8.2 Hz, 1H), 4.64 (br d, J=7.0 Hz, 2H), 3.99 (s, 3H), 3.74 (br s, 1H), 3.63-3.48 (m, 1H), 3.35-3.27 (m, 1H), 3.17-3.04 (m, 1H), 3.01 (br t, J=7.5 Hz, 2H), 2.56-2.52 (m, 3H), 2.23 (br s, 1H), 2.06-1.91 (m, 2H), 1.72 (br t, J=9.3 Hz, 1H), 1.49-1.39 (m, 1H), 1.23 (br d, J=8.4 Hz, 1H), 0.32 (br d, J=7.8 Hz, 2H), 0.23 (br s, 2H); LC/MS (M+H)=585.9; Retention Time=1.43 min (Method 1).

Example 2

((1R,4R,7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-((6-fluoropyridin-3-yl)oxy)-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-5-yl)methanone

(336) ##STR00196##

(337) A 1 dram vial was charged with tert-butyl ((1R,4R,7R)-2-(2-(6-bromo-1-(cyclopropylmethyl)-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carbonyl)-2-azabicyclo[2.2.1]heptan-7-yl)carbamate (0.037 g, 0.040 mmol), 2-fluoro-5-hydroxypyridine (5.42 mg, 0.048 mmol), cesium carbonate (0.020 g, 0.060 mmol) and Rockphos Pd G3 (3.35 mg, 3.99 μmol) in dioxane (1 mL). The vial was capped and the reaction mixture was made anaerobic by a pump/backfill with nitrogen cycle (5×). The reaction was set to stir at 90° C. overnight. After cooling, the mixture was diluted with EtOAc, dried (MgSO4), filtered, and concentrated. The resulting residue was dissolved in dichloromethane (1 mL) and treated with TFA (0.5 ml, 6.49 mmol). Mixture was stirred at rt for 90 min before it was concentrated. The residue was dissolved in DMF, filtered and purified via preparative LC/MS with the following conditions: Column: XBridge C18, 19×200 mm, 5-μm particles; Mobile Phase A: 5:95 acetonitrile:water with 10-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10-mM ammonium acetate; Gradient: 26-66% B over 20 minutes, then a 4-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation. The purified material was then diluted with DMF, treated with Si-Pyridine and shaken for a minimum of 2 h. The resulting mixture was filtered and concentrated via centrifugal evaporation to give ((1R,4R,7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-((6-fluoropyridin-3-yl)oxy)-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-5-yl)methanone (4.1 mg): .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 8.03 (br s, 1H), 7.72 (br d, J=8.5 Hz, 1H), 7.68 (br t, J=6.0 Hz, 1H), 7.44 (br s, 1H), 7.34 (s, 1H), 7.21 (br dd, J=8.7, 2.9 Hz, 1H), 7.06 (s, 1H), 6.95-6.90 (m, 2H), 4.37 (br d, J=6.4 Hz, 2H), 4.10 (s, 3H), 3.98 (s, 3H), 3.75 (br s, 1H), 3.66-3.48 (m, 1H), 3.17 (s, 1H), 3.08-2.99 (m, 1H), 2.21 (br s, 1H), 2.04-1.91 (m, 2H), 1.74 (br t, J=9.5 Hz, 1H), 1.48-1.40 (m, 1H), 1.23 (s, 2H), 1.04-0.94 (m, 1H), 0.26 (br d, J=7.9 Hz, 2H), −0.02 (br s, 2H); LC/MS (M+H)=581.3; Retention Time=1.75 min (Method 1).

Example 3

((1R,4R,7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(pyridin-4-ylthio)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-5-yl)methanone

(338) ##STR00197##

(339) A mixture of tert-butyl ((1R,4R,7R)-2-(2-(6-chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carbonyl)-2-azabicyclo[2.2.1]heptan-7-yl)carbamate (47 mg, 0.078 mmol), Pd2(dba)3 (14.22 mg, 0.016 mmol), (2R)-1-[(1R)-1-[bis (1,1-dimethylethyl)phosphino]ethyl]-2-(dicyclohexylphosphino)ferrocene (8.61 mg, 0.016 mmol) in DME (1.5 mL) was treated with potassium tert-butoxide (10.46 mg, 0.093 mmol). The vial was sealed and the reaction mixture was made anaerobic by a pump/backfill with nitrogen cycle (5×). The reaction was set to stir at rt for 10 min. The vial cap was opened under a nitrogen flush and treated with 4-mercaptopyridine (10.36 mg, 0.093 mmol). The vial was capped and made anaerobic by pump/backfill w/N2 (3×). The reaction mixture was stirred at 110° C. overnight. As per LCMS, desired product was observed along with some starting material. In order to gain more product, the reaction was repeated and the details follow: A mixture of tert-butyl ((1R,4R,7R)-2-(2-(6-chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carbonyl)-2-azabicyclo[2.2.1]heptan-7-yl)carbamate (110 mg, 0.182 mmol) (2R)-1-[(1R)-1-[bis (1,1-dimethylethyl)phosphino]ethyl]-2-(dicyclohexylphosphino)ferrocene (20.16 mg, 0.036 mmol), Pd2(dba)3 (33.3 mg, 0.036 mmol) in dioxane (2 mL) under a nitrogen flush was treated with potassium tert-butoxide (24.48 mg, 0.218 mmol). The vial was sealed and the reaction mixture was made anaerobic by a pump/backfill with nitrogen cycle (5×). The reaction was set to stir at rt for 10 min. The vial cap was opened under a nitrogen flush and treated with 4-mercaptopyridine (24.25 mg, 0.218 mmol). The vial was capped and made anaerobic by pump/backfill w/N2 (3×). The reaction mixture was stirred at 110° for 20 h. After cooling, the reaction was quenched with satd. NH4Cl aq. It was diluted with EtOAc and then washed with water followed by brine. The combined aq layer was extracted with EtOAc. The combined organic layer was dried (MgSO4). Crude products from the two experiments were combined and purified by flash chromatography (12 g ISCO cartridge was used with EtOAc-Hexanes). The product fractions were combined and concentrated (crude weight=0.1 g). The resulting residue was dissolved in DCM (1 mL) and treated with TFA (0.5 ml, 6.49 mmol). After 1 h, the solution was concentrated and the residue was dissolved the residue in DMF, filtered and purified via preparative LC/MS with the following conditions: Column: XBridge C18, 200 mm×19 mm, 5-μm particles; Mobile Phase A: 5:95 acetonitrile:water with 10-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10-mM ammonium acetate; Gradient: a 0-minute hold at 24% B, 24-64% B over 20 minutes, then a 4-minute hold at 100% B; Flow Rate: 20 mL/min; Column Temperature: 25 C. Fraction collection was triggered by MS and UV signals. Fractions containing the desired product were combined and dried via centrifugal evaporation. The purified material was then diluted with DMF, treated with Si-Pyridine and shaken for a minimum of 2 h. The resulting mixture was filtered and dried via centrifugal evaporation to give ((1R,4R,7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(pyridin-4-ylthio)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-5-yl)methanone (10.1 mg): .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 8.49 (br s, 2H), 8.21 (br d, J=7.9 Hz, 1H), 7.41-7.35 (m, 4H), 7.15 (s, 1H), 6.98-6.93 (m, 1H), 4.37 (br d, J=6.1 Hz, 2H), 4.14 (s, 3H), 4.00 (br s, 3H), 3.71 (br s, 2H), 3.57-3.47 (m, 1H), 3.10 (br d, J=11.0 Hz, 1H), 2.91 (s, 1H), 2.75 (s, 1H), 1.92 (br s, 4H), 1.48 (br t, J=8.4 Hz, 1H), 1.08-1.00 (m, 1H), 0.27 (br d, J=7.6 Hz, 2H), 0.00 (br s, 2H); LC/MS (M+H)=580.4; Retention Time=1.58 min (Method 1).

Example 4

((1R,4R,7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(pyridin-4-ylsulfonyl)-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-5-yl)methanone

(340) ##STR00198##

(341) A mixture of tert-butyl ((1R,4R,7R)-2-(2-(6-bromo-1-(cyclopropylmethyl)-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carbonyl)-2-azabicyclo[2.2.1]heptan-7-yl)carbamate (120 mg, 0.185 mmol), (2R)-1-[(1R)-1-[bis (1,1-dimethylethyl)phosphino]ethyl]-2-(dicyclohexylphosphino)ferrocene (20.52 mg, 0.037 mmol), Pd2(dba)3 (33.9 mg, 0.037 mmol) in dioxane (2 mL) under a nitrogen flush was treated with potassium tert-butoxide (24.91 mg, 0.222 mmol). The vial was sealed and the reaction mixture was made anaerobic by a pump/backfill with nitrogen cycle (5×). The reaction was stirred at rt for 10 min. The vial cap was opened under a nitrogen flush and treated with 4-mercaptopyridine (30.8 mg, 0.278 mmol). The vial was capped and made anaerobic by pump/backfill w/N2 (3×). The reaction mixture was stirred at 110° C. overnight. The reaction was quenched with satd. NH4Cl aq. It was diluted with EtOAc and then washed with water followed by brine. The combined aq layer was extracted with EtOAc. The combined organic layer was dried (MgSO4), filtered, and concentrated. The resulting residue was purified by flash chromatographed (EtOAc/Hexane) to yield tert-butyl ((1R,4R,7R)-2-(2-(1-(cyclopropylmethyl)-6-(pyridin-4-ylthio)-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carbonyl)-2-azabicyclo[2.2.1]heptan-7-yl)carbamate (38 mg, 0.056 mmol, 30.3% yield) as a brownish oil which was dissolved in acetone (1.5 mL) and was treated with water (1.500 ml) followed by oxone (103 mg, 0.168 mmol). This was stirred overnight. The reaction was diluted with EtOAc and then washed with 1.5M K2HPO4 aq followed by brine. The combined aq layer was extracted with EtOAc. The combined organic layer was dried (MgSO4), filtered and concentrated. The resulting residue was dissolved in CH2Cl2 (1 mL) and treated with TFA (0.5 ml, 6.49 mmol). After stirring for 1 h, the deprotection was found complete. Concentrated and dried in vacuo briefly. The residue was dissolved in DMF and purified via preparative LC/MS with the following conditions: Column: XBridge C18, 200 mm×19 mm, 5-μm particles; Mobile Phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid; Mobile Phase B: 95:5 acetonitrile:water with 0.1% trifluoroacetic acid; Gradient: a 0-minute hold at 12% B, 12-52% B over 20 minutes, then a 4-minute hold at 100% B; Flow Rate: 20 mL/min; Column Temperature: 25 C. Fraction collection was triggered by MS and UV signals. Fractions containing the desired product were combined and dried via centrifugal evaporation. The purified material was then diluted with DMF, treated with Si-Pyridine and shaken for a minimum of 2 h. The resulting mixture was filtered and dried via centrifugal evaporation to give ((1R,4R,7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(pyridin-4-ylsulfonyl)-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-5-yl)methanone (12.6 mg, 0.020 mmol, 10.8% yield): .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 8.80 (br d, J=5.5 Hz, 2H), 8.38 (br s, 1H), 7.90 (br d, J=5.2 Hz, 2H), 7.87 (br d, J=8.5 Hz, 1H), 7.62 (br d, J=8.5 Hz, 1H), 7.35 (s, 1H), 7.49-7.34 (m, 1H), 7.15 (s, 1H), 6.96-6.88 (m, 1H), 4.48 (br d, J=7.0 Hz, 2H), 4.02 (s, 3H), 3.93 (br s, 3H), 3.74-3.50 (m, 1H), 3.44-3.39 (m, 1H), 3.15-3.07 (m, 1H), 2.61 (br s, 1H), 1.96-1.77 (m, 3H), 1.65-1.52 (m, 1H), 1.01-0.94 (m, J=5.8 Hz, 1H), 0.26 (br d, J=7.6 Hz, 2H), 0.00 (br s, 2H); LC/MS (M+H)=611.37; Retention Time=1.45 min (Method 1).

Example 5

((1R,4R,7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-((4-hydroxyphenyl)amino)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-5-yl)methanone

(342) ##STR00199##

(343) A vial was charged with tert-butyl ((1R,4R,7R)-2-(2-(6-chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carbonyl)-2-azabicyclo[2.2.1]heptan-7-yl)carbamate (25 mg, 0.041 mmol), 4-aminophenol (6.76 mg, 0.062 mmol), cesium carbonate (40.4 mg, 0.124 mmol) and 2.sup.nd generation X-Phos precatalyst (3.25 mg, 4.13 μmol) in dioxane (1 mL) and tBuOH (0.25 mL). The vial was capped and the reaction mixture was made anaerobic by a pump/backfill with nitrogen cycle (5×). The reaction was stirred at 70° C. overnight. After cooling, the mixture was diluted with EtOAc and dried (MgSO4), filtered and concentrated. The resulting residue was dissolved in CH.sub.2Cl2 (1 mL) and treated with TFA (0.5 ml, 6.49 mmol). This mixture was stirred at rt for 2 hrs before it was concentrated. The resulting residue was dissolved in DMF and was purified via preparative LC/MS with the following conditions: Column: XBridge C18, 200 mm×19 mm, 5-μm particles; Mobile Phase A: 5:95 acetonitrile:water with 10-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10-mM ammonium acetate; Gradient: a 0-minute hold at 17% B, 17-57% B over 20 minutes, then a 4-minute hold at 100% B; Flow Rate: 20 mL/min; Column Temperature: 25 C. Fraction collection was triggered by MS and UV signals. Fractions containing the desired product were combined and dried via centrifugal evaporation. The purified material was then diluted with DMF, treated with Si-Pyridine and shaken for a minimum of 2 h. The resulting mixture was filtered and dried via centrifugal evaporation to give ((1R,4R,7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-((4-hydroxyphenyl)amino)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-5-yl)methanone (13.8 mg, 0.024 mmol, 57.8% yield): .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 8.83 (s, 1H), 7.75 (d, J=8.5 Hz, 1H), 7.56 (br d, J=8.9 Hz, 2H), 7.40-7.27 (m, 1H), 6.89-6.79 (m, 2H), 6.68 (br d, J=8.9 Hz, 2H), 6.59 (d, J=8.5 Hz, 1H), 4.39 (br d, J=6.7 Hz, 2H), 4.08 (s, 3H), 3.93 (s, 3H), 3.73 (br s, 1H), 3.65-3.42 (m, 1H), 3.16-2.95 (m, 2H), 2.22-2.07 (m, 1H), 2.00-1.87 (m, 2H), 1.77-1.60 (m, 1H), 1.44-1.28 (m, 1H), 1.11 (br s, 1H), 0.25 (br d, J=7.9 Hz, 2H), 0.13 (br d, J=4.0 Hz, 2H); LC/MS (M+H)=578.26; Retention Time=1.41 min (Method 1).

Intermediate 4

2-(5-((1R,4R,7R)-7-((tert-butoxycarbonyl)amino)-2-azabicyclo[2.2.1]heptane-2-carbonyl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-2-yl)-1-(cyclopropylmethyl)-1H-indole-6-carboxylic acid

(344) ##STR00200##

(345) To a solution of tert-butyl ((1R,4R,7R)-2-(2-(6-bromo-1-(cyclopropylmethyl)-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carbonyl)-2-azabicyclo[2.2.1]heptan-7-yl)carbamate (0.36 g, 0.555 mmol), DPPF (0.062 g, 0.111 mmol) and TEA (0.232 mL, 1.665 mmol) in DMF (2 mL) and MeOH (0.500 mL) was bubbled CO (g) for 5 min following which the reaction solution was treated with palladium (II) acetate (0.037 g, 0.056 mmol). CO (g) was bubbled for another min. The vial was sealed and a balloon containing carbon monoxide was connected to the vial via a needle. This was then stirred at 90° C.

(346) After stirring overnight, the reaction was found to be incomplete. Additional amounts of DPPF (0.062 g, 0.111 mmol), MeOH (0.500 mL) and palladium (II) acetate (0.037 g, 0.056 mmol) were added to the reaction and the solution was saturated with CO (g) by bubbling for 5 min. The vial was sealed and a CO (g) balloon was attached. The mixture was stirred at 90° C. for another 18 h. After cooling, the mixture was diluted with EtOAc and filtered through Celite. The mixture was then washed with 10% LiCl (aq) (2×) followed by brine. The combined aq. layer was extracted with EtOAc. The combined organic layer was dried (MgSO4), filtered and concentrated. The resulting residue was purified via flash chromatographed (EtOAc/Hexane) to give the methyl ester as a brown oil, which was then dissolved in THF (2 mL) and MeOH (0.5 mL). This solution was treated with 2M LiOH aq (0.555 mL, 1.110 mmol). The reaction was stirred at 70° C. for 2 h. The temperature was then raised to 80° C. After 1 h, the reaction was still not complete and 2M LiOH aq (0.278 mL, 0.555 mmol) was added and stirring was continued at 80° C. After 7 h the saponification was complete. After cooling, the mixture was diluted with EtOAc and 2M HCl was added (pH=5). The organic layer was separated and then washed with brine. It was dried (MgSO4), filtered, and concentrated to give the intermediate 2-(5-((1R,4R,7R)-7-((tert-butoxycarbonyl)amino)-2-azabicyclo[2.2.1]heptane-2-carbonyl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-2-yl)-1-(cyclopropylmethyl)-1H-indole-6-carboxylic acid: LC/MS (M+H)=614.3; Retention Time=0.87 min (Method 3).

Example 6

2-(5-((1R,4R,7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-2-yl)-1-(cyclopropylmethyl)-N-(pyridin-4-yl)-1H-indole-6-carboxamide

(347) ##STR00201##

(348) A mixture of 2-(5-((1R,4R,7R)-7-((tert-butoxycarbonyl)amino)-2-azabicyclo[2.2.1]heptane-2-carbonyl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-2-yl)-1-(cyclopropylmethyl)-1H-indole-6-carboxylic acid (30 mg, 0.049 mmol—from the above procedure), 4-aminopyridine (4.38 μl, 0.059 mmol) and Hunig's Base (0.026 ml, 0.147 mmol) in DMF (1 mL) at rt was treated with HATU (22.30 mg, 0.059 mmol). The reaction was stirred overnight at rt. The reaction mixture was then diluted with EtOAc and washed with 10% LiCl (aq) followed by brine. The combined aq layer was extracted with EtOAc. The combined organic layer was dried (MgSO4), filtered, and concentrated. The resulting residue was dissolved in CH2Cl2 (1 mL) and treated with TFA (0.5 ml, 6.49 mmol). After stirring 1 h, the reaction was evaporated. This residue was dissolved in DMF and purified via preparative LC/MS with the following conditions: Column: XBridge C18, 19×200 mm, 5-μm particles; Mobile Phase A: 5:95 acetonitrile:water with 10-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10-mM ammonium acetate; Gradient: 14-54% B over 20 minutes, then a 4-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation. The purified material was then diluted with DMF, treated with Si-Pyridine and shaken for a minimum of 2 h. The resulting mixture was filtered and dried via centrifugal evaporation to give 2-(5-((1R,4R,7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-2-yl)-1-(cyclopropylmethyl)-N-(pyridin-4-yl)-1H-indole-6-carboxamide (5.9 mg, 10.01 μmol, 20.47% yield): .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 8.45 (br t, J=5.4 Hz, 1H), 8.16-8.13 (m, 1H), 7.71-7.67 (m, 1H), 7.65-7.60 (m, 1H), 7.44-7.31 (m, 1H), 7.02 (s, 1H), 6.95-6.88 (m, 1H), 4.41 (br d, J=6.7 Hz, 2H), 4.13 (br d, J=8.3 Hz, 1H), 4.06 (s, 3H), 3.95 (s, 3H), 3.78-3.66 (m, 3H), 3.61 (q, J=7.7 Hz, 1H), 3.49 (br dd, J=8.3, 5.4 Hz, 1H), 3.34-3.22 (m, 1H), 3.04 (br d, J=11.5 Hz, 1H), 2.52 (br s, 2H), 2.24-2.12 (m, 1H), 2.02-1.88 (m, 3H), 1.78-1.68 (m, 1H), 1.62 (dq, J=12.9, 6.5 Hz, 1H), 1.42 (br s, 1H), 1.20 (br s, 1H), 1.06 (br s, 1H), 0.28 (br d, J=7.8 Hz, 2H), 0.00 (br s, 2H); LC/MS (M+H)=590.36; Retention Time=1.25 min (Method 3).

Example 7

6-(2-(5-((1R,4R,7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-3,4-dihydroquinolin-2(1H)-one

(349) ##STR00202##

(350) A 2 dr vial was charged with ((1R,4R,7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(6-chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-5-yl)methanone (125 mg, 0.248 mmol), 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroquinolin-2(1H)-one (81 mg, 0.297 mmol), potassium phosphate tribasic, 3M in water (0.248 mL, 0.743 mmol) and 1,1′-Bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (20.21 mg, 0.025 mmol) in THF (2 mL). The vial was capped and the reaction mixture was made anaerobic by a pump/backfill with nitrogen cycle (5×). The reaction was stirred at 70° C. for overnight. After cooling, the mixture was concentrated and dried in vacuo. It was dissolved in DMF and purified via prep HPLC. Prep HPLC conditions: Start % B=20, Final % B=70, Gradient Time=15 min, Flow Rate=30 ml/min, Wavelength=254, Solvent Pair=MeCN-H20-TFA; Solvent A=0.1% TFA in water; Solvent B=0.1% TFA in MeCN; Column 2=1: Luna 5 u C18 30×100 mm AXIA Product eluted at 7.92 min. The desired fractions were combined and it was diluted with EtOAc and then washed with 1.5M K2HPO4 (aq) followed by brine. The combined aq layer was extracted with EtOAc. The combined organic layer was dried (MgSO4), filtered and concentrated. The residue was dissolved in DCM-MeOH and treated with 25 mgs of Py-resin. This was shaken for over 2 h before it was filtered and concentrated. The residue was dissolved into a mixture of water-acetonitrile, frozen and lyophilized to give 6-(2-(5-((1R,4R,7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-3,4-dihydroquinolin-2(1H)-one (55 mg, 0.086 mmol, 34.6% yield) as a white fluffy solid: .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 10.08 (s, 1H), 8.15 (d, J=8.2 Hz, 1H), 8.02-7.97 (m, 2H), 7.89-7.78 (m, 1H), 7.76-7.69 (m, 2H), 7.45 (br d, J=8.6 Hz, 1H), 7.10 (s, 1H), 7.01 (d, J=8.2 Hz, 1H), 4.64 (br d, J=7.0 Hz, 2H), 3.99 (s, 3H), 3.74 (br s, 1H), 3.63-3.48 (m, 1H), 3.35-3.27 (m, 1H), 3.17-3.04 (m, 1H), 3.01 (br t, 0.1=7.5 Hz, 2H), 2.56-2.52 (m, 3H), 2.23 (br s, 1H), 2.06-1.91 (m, 2H), 1.72 (br t, J=9.3 Hz, 1H), 1.49-1.39 (m, 1H), 1.23 (br d, J=8.4 Hz, 1H), 0.32 (br d, J=7.8 Hz, 2H), 0.23 (br s, 2H) LCMS=(M+H)+=616.3; retention time=0.7 min (Method 3).

Example 8

((1R,4R,7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(oxetan-3-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-5-yl)methanone

(351) ##STR00203##

(352) The tert-butyl ((1R,4R,7R)-2-(2-(6-chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carbonyl)-2-azabicyclo[2.2.1]heptan-7-yl)carbamate (30 mg, 0.050 mmol) was dissolved in dioxane (0.5 mL) prior to the addition of 3-bromooxetane (6.79 mg, 0.050 mmol), (Ir[DF(CF3)PPY]2(DTBPY))PF6 (1.112 mg, 0.992 μmol), sodium carbonate (0.011 mL, 0.198 mmol), 4,4′-di-tert-butyl-2,2′-bipyridine (0.798 mg, 2.97 μmol), tris(trimethylsilyl)silane (0.023 mL, 0.074 mmol), nickel (11) chloride ethylene glycol dimethyl ether complex (0.545 mg, 2.479 μmol) and a nitrogen purge followed. This was stirred overnight in front of two Kessil lamps with fan cooling of the reaction vial. After cooling EtOAc was added and this was filtered and concentrated. The resulting residue was dissolved in DCM (1 mL) prior to the addition of T-FA (2 mL). After 30 min, the mixture was concentrated. The resulting residue was purified via preparative LC/MS with the following conditions: Column: XBridge C18, 200 mm×19 mm, 5-μm particles; Mobile Phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid; Mobile Phase B: 95:5 acetonitrile:water with 0.1% trifluoroacetic acid; Gradient: a 0-minute hold at 10% B, 10-50% B over 20 minutes, then a 4-minute hold at 100% B; Flow Rate: 20 mL/min; Column Temperature: 25 C. Fraction collection was triggered by MS and UV signals. Fractions containing the desired product were combined and dried via centrifugal evaporation. The purified material was then diluted with DMF, treated with Si-Pyridine and shaken for a minimum of 2 h. The resulting mixture was filtered and dried via centrifugal evaporation to give ((1R,4R,7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(oxetan-3-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-5-yl)methanone (5.8 mg, 0.01 mmol, 22.2%): .sup.1H NMR (500 MHz, DMSO-d.sub.6, rotamers) S 8.07-8.00 (m, 1H), 7.44 (m, 0.33H), 7.36-7.31 (m, 0.71H), 7.14-7.08 (m, 1H), 7.03-6.99 (m, 1H), 6.95-6.85 (m, 1H), 4.94-4.89 (m, 2H), 4.88-4.83 (m, 2H), 4.52-4.42 (m, 3H), 4.14 (m, 0.25H), 4.07 (s, 3H), 3.94 (s, 3H), 3.79-3.72 (m, 0.53H), 3.52-3.38 (m, 1H), 3.18-3.11 (m, 0.49H), 3.07-2.95 (m, 1H), 2.22 (m, 0.76H), 2.14 (m, 0.41H), 1.99-1.78 (m, 2H), 1.77-1.62 (m, 1H), 1.48-1.30 (m, 11H), 1.13-1.01 (m, 1H), 0.32-0.20 (m, 2H), 0.17-0.06 (m, 2H); LCMS (M+H)+=527.4; Retention Time: 1.37 min (Method 1).

(353) The Examples in the tables below were prepared in the same manner as that outlined for Examples 1-8 above.

(354) TABLE-US-00001 TABLE 1 HPLC Obs. Method RT Cmpd # Structure Name MS Ion IDs (min) 9. 04 (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(pyridin-4-yl)- lH-pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 548 1 1.6 10. 05 (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(2- methoxypyridin-4-yl)-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl- 1H-1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 578.3 1 1.76 11. 06 N-[3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6- yl)phenyl]methanesulfonamide 640.2 2 1.41 12. 07 methyl N-[5-(2-{5-[(1R,4R,7R)-7- amino-2-azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H-1,3 benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridin-2-yl]carbamate 621.2 1 1.57 13. 08 (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(1-methyl-1H- pyrazol-5-yl)-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl- 1H-1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 551 2 1.47 14. 09 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicydo[2.2.1]heplane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3-dihydro-1H-1,3- benzodiazol-2-one 603.1 1 1.31 15. 0 (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(2- methoxypyridin-4-yl)-1H-indol-2-yl]- 7-methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicydo[2.2.1]heptan-7-amine 577.2 2 1.4 16. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-lH-indol-6-yl)-1- methyl-1,2-dihydropyridin-2-one 577.1 1 1.34 17. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(5- methoxypyridin-3-yl)-1H-indol-2-yl]- 7-methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 577.3 1 1.57 18. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(1-methyl-1H- pyrazol-5-yl)-1H-indol-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 550.4 1 1.42 19. methyl N-[5-(2-{5-[(1R,4R,7R)-7- amino-2-azabicyclo[2.2.1]heptane-2- carbonyl]-7-mcthoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6- yl)pyridin-2-yl]carbamate 620.2 2 1.26 20. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(3,5-dimethyl- 1,2-oxazol-4-yl)-1H-indol-2-yl]-7- methoxy-1-methyl-1H-l,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 565.4 2 1.46 21. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(3-methyl-1H- pyrazol-yl)-1H-indol-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 550.4 1 1.32 22. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(pyridin-3-yl)- lH-indol-2-yl]-7-methoxy-1-methyl- 1H-1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 547.4 1 1.49 23. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(1-methyl-1H- pyrazol-4-yl)-1H-indol-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.l]heptan-7-amine 550.2 1 1.77 24. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(1H-pyrazol-4- yl)-1H-indol-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5- carbonyl}-2-azabicyclo[2.2.1]heptan-7- amine 536.3 1 1.22 25. 0 (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(pyridin-3- yloxy)-1H-indol-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5- carbonyl}-2-azabicyclo[2.2.1]heptan-7- amine 563 1 1.53 26. 2-methoxyethyl N-[5-(2-{5- [(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6- yl)pyridin-2-yl]carbamate 664.4 1 1.59 27. 2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-N-(pyridin-4-yl)- 1H-indol-6-amine 562.3 1 1.15 28 3-[4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 1H-pyrazol-1-yl]propanamide 607.1 1 1.18 29. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(1H-pyrazol-3- yl)-1H-indol-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5- carbonyl}-2-azabicyclo[2.2.1]heptan-7- amine 536.3 1 1.39 30. 2-{[4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H,1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6- yl)phenyl]foramido}acetic acid 647.1 1 1.15 31. 3-{[4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H,1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6- yl)phenyl]foramido}propanpoic acid 661.2 1 1.19 32. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)-N- (pyridin-4-yl)benzamide 666 2 1.2 33. 2-{5-[(1R,4R,7R)-7-amino-2- azabicycio[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-N-(pyrimidin-5- yl)-lH-indol-6-amine 563.3 2 1.07 34. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-[(pyridin-4- yl)amino]-1H-pyrrolo[2,3-b]pyridin-2- yl]-7-methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 1 35. 0 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6- yl)benzamide 589.4 1 1.42 36. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(3,5-dimethyl- 1H-pyrazol-4-yl)-1H-indol-2-yl]-7- methoxy-1-methyl-1H-l,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 564.4 1 1.36 37. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(3-methyl-1H- pyrazol-4-yl)-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl- 1H-1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 551.3 1 1.32 38. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(3,5-dimethyl- 1,2-oxazol-4-yl)-1H-pyrrolo[2,3- b]pyridin-yl]-7-methoxy-1-methyl- 1H-1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 566.3 1 1.62 39. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(5- methoxypyridin-3-yl)-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl- 1H-1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.l]heptan-7-amine 577.9 1 1.55 40. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1-methyl-1,2- dihydropyridin-2-one 578.1 2 1.16 41. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(3,5-dimethyl- 1H-pyrazol-4-yl)-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl- 1H-1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 565.2 1 1.38 42. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(1H-pyrrol-3- yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl)-2- azabicyclo[2.2.l]heptan-7-amine 536.1 2 1.25 43. 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl)-1- (cyclopropylmethyl)-1H-indol-6- yl)pyrimidine-2-carbonitrile 573.4 1 1.64 44. 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyrimidine-2- carbonitrile 574.1 1 1.61 45. 0 5-[(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6- yl)amino]pyrimidine-2-carbonitrile 588.4 2 1.36

(355) TABLE-US-00002 TABLE 2 Obs. HPLC MS Method RT Cmpd # Structure Name Ion IDs (min) 46. 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2,3,4- tetrahydropyrimidine-2,4-dione 581.4 1 1.12 47. N-[4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6- yl)phenyl]but-2-ynamide 627.2 1 1.66 48. N-[4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6- yl)phenyl]prop-2-enamide 615.2 2 1.44 49. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-[(2,6- dimethylpyridin-4-yl)amino]-1H- pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 591.4 1 1.2 50. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(2- methylpyridin-4-yl)-1H-pyrrolo(2,3- b]pyridin-2-yl]-7-methoxy-1-methyl- 1H-1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 562.2 1 1.53 51. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(6- methoxypyridin-3-yl)-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl- 1H-1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 578 1 1.96 52. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-[(2- methylpyridin-4-yl)amino]-1H- pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 577 1 1.4 53. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)benzamide 590.3 2 1.2 54. (1R,4R,7R)-2-{2-[6-(6-aminopyridin- 3-yl)-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 563.4 2 1.01 55. 0 (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-[2- (methylamino)pyrimidin-5-yl]-1H- pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 578.3 1 1.48 56. 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridine-2- carboxamide 591.1 1 1.41 57. (1R,4R,7R)-2-{2-[1- (cyclopropylmethy))-6-(2-fluoro-3- methylpyridin-4-yl)-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl- 1H-1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 580.4 2 1.56 58. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-chlorobenzamide 624.3 1 1.42 59. (1R,4R,7R)-2-(2-{6-[(3- chloropyridin-4-yl)amino]-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-2-yl}-7-methoxy-1-methyl- 1H-1,3-benzodiazole-5-carbonyl)-2- azabicyclo[2.2.1]heptan-7-amine 597.3 1 1.67 60. 2-{3-[(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)amino]-1H-pyrazol-1- yl}ethan-1-ol 596.2 1 1.22 61. methyl 4-[(2-{5-[(1R,4R,7R)-7- amino-2-azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)amino]pyridine-3- carboxylate 621.4 2 1.15 62. 4-[(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)amino]benzonitrile 587.4 1 1.75 63. (1R,4R,7R)-2-(2-{6-((3-chloro-2- methylpyridin-4-yl)amino]-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-2-yl}-7-methoxy-1-methyl- 1H-1,3-benzodiazole-5-carbonyl)-2- azabicyclo[2.2.1]heplan-7-amine 611.1 1 1.76 64. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-[(3,5- dimethylpyridin-4-yl)amino]-1H- pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 591.1 2 0.99 65. 0 (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-[(2,3- dimethylpyridin-4-yl)amino]-1H- pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 591.5 2 1.1 66. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-[(3- methylpyridin-4-yl)amino]-1H- pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-l,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 577.2 1 1.25 67. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-[(3- fluoropyridin-4-yl)amino]-1H- pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 581.3 2 0.97 68. N-(2-{5-[(3R)-3-aminopiperidine-1- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-methylpyridin-4- amine 565.2 2 1.1 69. N-(2-{5-[(3R)-3-aminopiperidine-1- carbonyl)-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3-dimethylpyridin-4- amine 579.2 2 1.14 70. N-(2-{5-[(3R)-3-aminopiperidine-1- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridin-4-amine 551.1 1 1.13 71. N-(2-{5-[(3R)-3-aminopiperidine-1- carbonyl]-7-methoxy-1-methyl-1H- l,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-methylpyridin-4- amine 565.4 2 0.96 72. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-[(6- methylpyridin-3-yl)amino]-1H- pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 577.4 1 1.54 73. 4-[(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)amino]pyridine-2- carbonitrile 588.2 1 1.54 74. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6- [methyl(pyridin-4-yl)amino]-1H- pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 577.4 2 1 75. 0 {4-[(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)amino]pyridin-3- yl}methanol 593.2 2 1.21 76. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-[(2- methoxypyrimidin-4-yl)amino]-1H- pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 594.2 1 1.6 77. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-{[2-(propan-2- yl)pyrimidin-4-yl]ammo}-1H- pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl)-2- azabicyclo[2.2.1]heptan-7-amine 606.2 1 1.84 78. N4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyrimidine-4,6-diamine 579.5 1 1.2 79. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-[(2- methylpyrimidin-4-yl)amino]-1H- pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 578.2 1 1.54 80. 6-[(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)amino]pyrimidin-4-ol 580.1 1 1.29 81. 5-[(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)amino]pyridine-2- carbonitrile 588.2 2 1.46 82. N5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridine-2,5-diamine 578.4 1 1.22 83. N1-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)benzene-1,4-diamine 577.4 2 0.93 84. N1-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)benzene-1,3-diamine 577.3 1 1.44 85. 0 4-[(2-(5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)amino]benzamide 605.4 1 1.34 86. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(1-methyl- 1,2,3,6-tetrahydropyridin-4-yl)-1H- pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 566.6 1 1.17 87. (1R,4R,7R)-2-{2-[1- (cyclopropytmethyl)-6-[4-(5-methyl- 1,3,4-oxadiazol-2-yl)phenyl]-1H- pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 629.2 2 1.55 88. (1R,4R,7R)-2-(2-{6-[4-(5-amino- 1,3,4-thiadiazol-2-yl)phenyl)-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-2-yl}-7-methoxy-1-methyl- 1H-1,3-benzodiazole-5-carbonyl)-2- azabicyclo[2.2.1]heptan-7-amine 646.2 1 1.72 89. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenol 563.4 1 1.56 90. 3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- bcnzodiazol-2-yl)-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenol 563.2 2 1.46 91. [3-{2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]methanol 576.9 2 1.42 92. 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridine-2-carbonitrile 573.2 2 1.52 93. [4-(2-(5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]methanol 577.5 2 1.35 94. methyl 5-(2-{5-[(1R,4R,7R)-7-amino- 2-azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl)-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pvridine-2-carboxylate 606.2 1 1.65 95. 0 (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(2,5-dihydro- 1H-pyrrol-3-yl)-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl- 1H-1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 538.4 1 1.03 96. N-[3-(2-(5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]ethene-1- sulfonamide 652.5 2 1.57 97. 3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-N-[2- (dimethylamino)ethyl]benzamide 661.5 1 1.28 98. 4-[(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)amino]pyridin-2-ol 579.4 1 1.15 99. 3-[(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)amino]phenol 578.4 2 1.26 100. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-[(2,5- dimethylpyridin-4-yl)amino]-1H- pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 591.5 1 1.26 101. 3-[(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-lH-indol-6- yl)amino]phenol 577.4 1 1.53 102. 2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heplane-2-carbonyl]- 7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-N-(2,5- dimethylpyridin-4-yl)-1H-indol-6- amine 590.5 1 1.17 103. (1R,4R,7R)-2-{2-[6-(3-aminophenyl)- 1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 562.4 2 1.07

(356) TABLE-US-00003 TABLE 3 HPLC RT Cmpd # Structure Name Obs. MS Ion Method IDs (min) 104. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-N-(2- hydroxyethyl)benzamide 634.1 1 1.46 105. 00 {4-[(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)amino]pyridin-2- yl}methanol 593.2 2 1.13 106. 01 [5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridin-2-yl]methanol 578.5 1 1.35 107. 02 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-fluorophenol 581.4 2 1.4 108. 03 (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(4- methoxyphenyl)-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl- 1H-1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 577.2 1 1.96 109. 04 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-N,N- dimethylbenzamide 618.5 2 1.38 110. 05 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-methoxyphenol 593.4 2 1.39 111. 06 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-chlorophenol 597.4 2 1.49 112. 07 (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-[1-(propan-2- yl)-1H-pyrazol-4-yl]-1H- pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 579.4 1 1.65 113. 08 (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-[1-(2- methylpropyl)-1H-pyrazol-3-yl]-1H- pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 593.5 1 1.83 114. 09 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-N,N- dimethylpyridine-2-carboxamide 619.2 1 1.39 115. 0 methyl 5-[(2-{5-[(1R,4R,7R)-7- amino-2-azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)amino]pyridine-2- carboxylate 621.2 2 1.26 116. 1-[3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]-3- methylidenepyrrolidin-2-one 642.2 2 1.54 117. N-[3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-methylphenyl]-N- methylprop-2-enamide 644.2 1 1.93 118. N-[3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-methylphenyl]-3- methylbut-2-enamide 658.2 2 1.53 119. N-[3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6- yl)phenyl]prop-2-enamide 615.2 1 1.9 120. N-[3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-fluorophenyl]-N- methylethene-1-sulfonamide 683.9 1 2.01 121. 1-[3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6- yl)phenyl]-3-methylidenepyrrolidin- 2-one 641.2 1 1.97 122. N-[3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6- yl)phenyl]-N-methylprop-2-enamide 629.2 1 1.9 123. 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 2,3-dihydro-1H-isoindol-1-one 601.1 1 1.53 124. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-[6- (methylsulfanyl)pyridin-3-yl]-1H- indol-2-yl]-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 593.3 2 1.62 125. 0 3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6- yl)benzoic acid 590.2 2 1.5 126. ethyl 5-(2-{5-[(1R,4R,7R)-7-amino- 2-azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1H-indole-2- carboxylate 329.7 2 1.81 127. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(6- methanesulfonylpyridin-3-yl)-1H- pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2,2,1]heptan-7-amine 626.4 1 1.61 128. 2-methoxyethyl N-[5-(2-{5- [(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridin-2- yl]carbamate 333.2 1 1.75 129. 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3-dihydro-1H- isoindol-1-one 602.2 2 1.41 130. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(1,3,5- trimethyl-1H-pyrazol-4-yl)-1H- pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 579.4 1 1.75 131. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(1,3- dimethyl-1H-pyrazol-4-yl)-1H- pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 565.4 1 1.52 132. (1R,4R,7R)-2-{2-[6-(1-cyclopropyl- 1H-pyrazol-4-yl)-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl- 1H-1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 577.4 2 1.51 133. (1R,4R,7R)-2-(2-{6-[4- (aminomethyl)phenyl]-1- (cyclopropylmethy)-1H-pyrrolo[2,3- b]pyridin-2-yl}-7-methoxy-1- methyl-1H-1,3-benzodiazole-5- carbonyl)-2-azabicyclo[2.2.1]heptan- 7-amine 576.5 1 1.27 134. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(1,2,3,4- tetrahydroquinolin-7-yl)-1H- pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 602.2 1 2.13 135. 0 (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-{1H- pyrrolo[2,3-b]pyridin-5-yl}-1H- pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine  587.2, 587.2 1 136. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(1-methyl- 1H-indol-5-yl)-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl- 1H-1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 600.4 2 1.7 137. N-[3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]-2- methylprop-2-enamide 630.5 1 1.8 138. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(1H-indazol- 5-yl)-1H-pyrrolo-[2,3-b]pyridin-2- yl]-7-methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 587.4 1 1.58 139. 5-[(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)amino]pyrimidine-2- carboxamide 607.1 1 1.34 140. 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6- yl)pyrimidine-2-carboxamide 591.1 1 1.38 141. {5-[(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)amino]-1-methyl-1H- 1,3-benzodiazol-2-yl}methanol 646.5 2 1.08 142. 6-[(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)amino]-2,3-dihydro- 1,3-benzoxazol-2-one 619.4 2 1.24 143. 5-[(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)amino]-2,3-dihydro- 1H-isoindol-1-one 617.5 1 1.51 144. 5-[(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)amino]-2-methyl-2,3- dihydro-1H-isoindol-1-one 631.5 1 1.52 145. 0 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2,3,4- tetrahydroisoquinolin-1-one 616.5 2 1.33 146. (1R,4R,7R)-2-{2-[6-(1-benzofuran- 5-yl)-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 587.4 1 2.1 147. 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3-dihydro-1H- indol-2-one 602.4 2 1.29 148. 1-[4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]ethan-1-ol 591.5 2 1.46 149. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(2,3-dihydro- 1-benzofuran-5-yl)-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl- 1H-1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 589.4 1 2.02 150. 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,3-dihydro-2- benzofuran-1-one 603.4 1 1.61 151. 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-methyl-2,3- dihydro-1H-isoindol-1-one 616.5 1 1.57 152. 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3-dihydro-1H- isoindol-1-one 602.4 1 1.48

(357) TABLE-US-00004 TABLE 4 HPLC RT Cmpd # Structure Name Obs. MS Ion Method IDs (min) 153. cyclopropylmethyl N-[4-(2-{5- [(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]carbamate 660.5 1 2.03 154. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(2,3-dihydro- 1,4-benzodioxin-6-yl)-1H- pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 605.4 2 1.68 155. 0 (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-[4- (ethanesulfonyl)phenyl]-1H- pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 639.4 2 1.52 156. 5-[4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]imidazolidine- 2,4-dione 645.4 2 1.19 157. 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3-dihydro-1H- indol-2-one 602.4 1 1.51 158. methyl 5-[(2-{5-[(1R,4R,7R)-7- amino-2-azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)amino]pyrimidine-2- carboxylate 622.5 1 1.36 159. 1-{6-[(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)amino]-2,3-dihydro- 1H-indol-1-yl}ethan-1-one 645.5 2 1.32 160. 1-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6- yl)piperazin-2-one 568.5 1 1.11 161. methyl N-[4-(2-{5-[(1R,4R,7R)-7- amino-2-azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3- methylphenyl]carbamate 634.3 2 1.5 162. [4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]urea 605.2 1 1.37 163. 3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)benzamide 590 1 1.57 164. 3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-N-methylbenzamide 604.4 1 1.5 165. 0 3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-N,N- dimethylbenzamide 618.3 2 1.39 166. [2-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-6- methoxyphenyl]methanol 607 1 1.65 167. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,6-difluorophenol 598.9 1 1.78 168. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 2,6-difluorophenol 598.4 2 1.49 169. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 2-chlorophenol 596.4 2 1.52 170. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7- methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-chlorophenol 603.4 2 1.55 171. 6-[(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)amino]-1,2,3,4- tetrahydroquinolin-2-one 631.2 2 1.32 172. [2-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-5- methoxyphenyl]methanol 607.5 2 1.52 173. (1R,4R,7R)-2-{2-[6-(4-amino-3- fluorophenyl)-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl- 1H-1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 580.2 2 1.41 174. (1R,4R,7R)-2-{2-[6-(4-amino-3- fluorophenyl)-1- (cyclopropylmethyl)-1H-indol-2-yl]- 7-methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 579.5 1 1.74 175. 0 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 2-fluorophenol 580.4 1 1.66 176. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7- methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-fluorophenol 587.4 2 1.47 177. methyl N-[4-(2-{5-[(1R,4R,7R)-7- amino-2-azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]carbamate 620.5 1 1.73 178. methyl N-[4-(2-{5-[(1R,4R,7R)-7- amino-2-azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6- yl)phenyl]carbamate 619.2 2 1.66 179. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 3-chlorophenol 596 1 1.86 180. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 3,5-difluorophenol 598.4 1 1.65 181. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 2,5-difluorophenol 597.9 1 1.85 182. [4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 2,6-difluorophenyl]methanol 611.9 2 1.5 183. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-chlorophenol 597.3 2 1.46 184. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3,5-difluorophenol 599 1 1.76 185. 0 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,5-difluorophenol 599.2 2 1.48 186. [4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,6- difluorophenyl]methanol 613.2 1 1.82 187. 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 1,2,3,4-tetrahydroquinolin-2-one 615.5 2 1.34 188. 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7- methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2,3,4- tetrahydroquinolin-2-one 622 1 1.66 189. 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 1,3-dihydro-2-benzofuran-1-one 602.5 2 1.48 190. 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 1H,2H,3H-imidazo[4,5-b]pyridin-2- one 603 2 1.23 191. 2′-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1′- (cyclopropylmethyl)-1-methyl-2,3- dihydro-1H,1′H-[5,6′-biindole]-2-one 615.4 1 1.77 192. methyl N-[5-(2-{5-[(3R,5R)-3- amino-5-fluoropiperidine-1- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridin-2- yl]carbamate 626.9 2 1.48 193. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3-dihydro-1H- isoindol-1-one 602.5 2 1.33 194. 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4-methyl-1,2- dihydroquinolin-2-one 628.5 1 1.51 195. 0 (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(2- methoxypyrimidin-5-yl)-1H- pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 579.3 1 1.55 196. 7-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2,3,4- tetrahydroquinolin-2-one 616.4 1 1.55 197. 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-methyl-1,2,3,4- tetrahydroquinazolin-2-one 631.3 2 1.33 198. 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2,3,4- tetrahydroquinolin-2-one 616.5 1 1.5 199. 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4,4-dimethyl-1,2,3,4- tetrahydroquinazolin-2-one 644.4 1 1.73 200. 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2,3,4- tetrahydroquinazoline-2,4-dione 631.4 2 1.19

(358) TABLE-US-00005 TABLE 5 HPLC Cmpd # Structure Name Obs. MS Ion Method IDs RT (min) 201. 2-amino-3-[4-(2-{5-[(1R,4R,7R)-7- amino-2-azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]propanoic acid 634.5 2 1.12 202. N-{[4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6- yl)phenyl]methyl}acetamide 618.5 1 1.29 203. N-{[4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6- yl)phenyl]methyl}methanesulfonamide 654.2 2 1.52 204. methyl 6-(2-{5-[(1R,4R,7R)-7- amino-2-azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-oxo-1,2- dihydroquinoline-4-carboxylate 672.1 2 1.7 205. 00 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4-hydroxy-3-methyl- 1,2-dihydroquinolin-2-one 644.4 1 1.21 206. 01 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2-dihydroquinolin- 2-one 614.3 2 1.45 207. 02 N-{[4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6- yl)phenyl]methyl}acetamide 617.1 1 1.48 208. 03 N-{[4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6- yl)phenyl]methyl}methanesulfonamide 653.2 2 1.83 209. 04 methyl 6-(2-{5-[(1R,4R,7R)-7- amino-2-azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 2-oxo-1,2-dihydroquinoline-4- carboxylate 671.3 2 1.72 210. 05 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 4-hydroxy-3-methyl-1,2- dihydroquinolin-2-one 643.2 1 1.21 211. 06 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 1,2-dihydroquinolin-2-one 613.1 1 1.45 212. 07 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,3-dihydro-2- benzofuran-1-one 603.4 2 1.78 213. 08 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1-methyl-2,3- dihydro-1H-indol-2-one 616.5 1 1.42 214. 09 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxyl-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2,3,4-tetrahydro- 1,8-naphthyridin-2-one 617.2 2 1.64 215. 0 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1H,2H,3H- pyrrolo[2,3-b]pyridin-2-one 603.4 2 1.32 216. 7-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2-dihydroquinolin- 2-one 614.1 1 1.53 217. 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2- dihydroisoquinolin-1-one 614.1 2 1.6 218. 2-[4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]acetic acid 605.3 1 1.57 219. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6- yl)benzene-1,3-diol 578 1 1.28 220. 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 1,2-dihydroisoquinolin-1-one 613.4 2 1.5 221. 7-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 1,2-dihydroquinolin-2-one 613.4 1 1.35 222. 2′-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1′- (cyclopropylmethyl)-2,3-dihydro- 1H,1′H-[6,6′-biindole]-2-one 601.5 1 1.33 223. 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 3-methyl-1,2,3,4- tetrahydroquinazolin-2-one 630.5 2 1.52 224. 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 1,2,3,4-tetrahydroquinolin-2-one 615.5 1 1.36 225. 0 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 4,4-dimethyl-1,2,3,4- tetrahydroquinolin-2-one 643.2 1 1.61 226. 2-[4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]acetamide 604.2 2 1.51 227. 2-[4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]-N- methylacetamide 618.2 1 1.38 228. 2-[4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-phenyl]-N-(2- hydroxyethyl)acetamide 648.2 1 1.31 229. 2-[4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]-N-(2- methanesulfonylethyl)acetamide 710.3 1 1.38 230. 7-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 1,2,3,4-tetrahydroquinazoline-2,4- dione 629.9 2 1.54 231. 7-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2,3,4- tetrahydroquinazoline-2,4-dione 631.2 2 1.5 232. N-[4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]acetamide 604.1 1 1.42 233. 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4-(hydroxymethyl)- 1,2-dihydroquinolin-2-one 644.4 1 1.29 234. 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-fluoro-8-methyl- 1,2-dihydroquinolin-2-one 646.2 1 1.42 235. 0 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2-dihydropyridin-2- one 564.6 2 1.24 236. N-[5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridin-2- yl]acetamide 605.1 1 1.28 237. 2-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 1,2-dihydropyridin-2-one 563.1 2 1.41 238. N-[5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6- yl)pyridin-2-yl]acetamide 604.2 1 1.13 239. N-[4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6- yl)phenyl]acetamide 603.1 1 1.43 240. N-[4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6- yl)phenyl]methanesulfonamide 639.3 1 1.37 241. 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 4-methyl-1,2-dihydroquinolin-2-one 627.2 1 1.31 242. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazo1-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 2,3-dihydro-1H-isoindol-1-one 601.6 2 1.49 243. 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 4-(hydroxymethyl)-1,2- dihydroquinolin-2-one 643.2 2 1.44 244. 7-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 1,2,3,4-tetrahydroquinolin-2-one 615.1 1 1.51 245. 0 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 1,2,3,4-tetrahydroquinazoline-2,4- dione 630.2 2 2.12 246. 7-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3,4-dihydro-2H-1,4- benzoxazin-3-one 617.9 2 1.71 247. methyl N-[4-(2-{5-[(1R,4R,7R)-7- amino-2-azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2- fluorophenyl]carbamate 638.5 1 1.62 248. N-[4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H- 1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2- chlorophenyl]methanesulfonamide 674.1 2 1.86

(359) TABLE-US-00006 TABLE 6 Comp. # Structure Name Obs. MS Ion HPLC Method IDs RT (min) 249. methyl N-[4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3- difluorophenyl]carbamate 656.1 1 1.84 250. 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2,3,4- tetrahydroquinazoline-2,4-dione 631.5 2 1.22 251. 7-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 3,4-dihydro-2H-1,4-benzoxazin-3-one 617.2 1 1.73 252. methyl N-[4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 2-fluorophenyl]carbamate 637.5 2 1.61 253. N-[4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 2-chlorophenyl]methanesulfonamide 673.2 1 1.88 254. methyl N-[4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 2,3-difluorophenyl]carbamate 655.2 1 1.91 255. 0 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 1,2,3,4-tetrahydroquinazoline-2,4-dione 630.5 2 1.26 256. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3,5-difluorophenol 605.1 2 1.58 257. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-chlorophenol 603.3 2 1.58 258. 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4-hydroxy-3-methyl-1,2- dihydroquinolin-2-one 650.1 2 1.41 259. 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2,3,4- tetrahydroquinazoline-2,4-dione 637.1 2 1.35 260. 2-amino-4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2,1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenol 578.4 1 1.34 261. (1R,4R,7R)-2-{2-[1-(cyclopropylmethyl)-6- (isoquinolin-6-yl)-1H-pyrrolo[2,3-b]pyridin- 2-yl]-7-methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 598.2 2 1.26 262. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl acetate 605.2 1 1.94 263. (1R,4R,7R)-2-{2-[6-(3-chloro-4- methoxyphenyl)-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 611.4 1 2.05 264. (1R,4R,7R)-2-{2-[1-(cyclopropylmethyl)-6- (2-fluoro-4-methoxyphenyl)-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 595.3 1 2.01 265. 0 (1R,4R,7R)-2-{2-[6-(3-chloro-4- fluorophenyl)-1-(cyclopropylmethyl)-1H- indol-2-yl]-7-methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 598.1 1 1.97 266. (1R,4R,7R)-2-{2-[6-(3-chloro-4,5- difluorophenyl)-1-(cyclopropylmethyl)-1H- indol-2-yl]-7-methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 616.4 1 2.38 267. (1R,4R,7R)-2-{2-[1-(cyclopropylmethyl)-6- (2-fluoro-4-methoxyphenyl)-1H-indol-2-yl]- 7-methoxy-1-methyl-1H-1,3-benzodiazole- 5-carbonyl}-2-azabicyclo[2.2.1]heptan-7- amine 594.1 1 2.02 268. (1R,4R,7R)-2-{2-[6-(1,3-benzothiazol-5-yl)- 1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 604.5 1 1.87 269. (1R,4R,7R)-2-{2-[1-(cyclopropylmethyl)-6- (1,3-thiazol-5-yl)-1H-pyrrolo[2,3-b]pyridin- 2-yl]-7-methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 554.4 1 1.59 270. (1R,4R,7R)-2-{2-[1-(cyclopropylmethyl)-6- (3-fluoro-4-methoxyphenyl)-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 595.5 2 1.74 271. (1R,4R,7R)-2-{2-[6-(2-chloro-4- methoxyphenyl)-1-(cyclopropylmethyl)-1H- pyrro1o[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 611.1 2 1.88 272. (1R,4R,7R)-2-{2-[6-(1,3-benzothiazol-5-yl)- 1-(cyclopropylmethyl)-1H-indol-2-yl]-7- methoxy-1-methyl-1H-1,3-benzodiazole-5- carbonyl}-2-azabicyclo[2.2.1]heptan-7- amine 603.2 1 2.03 273. (1R,4R,7R)-2-{2-[1-(cyclopropylmethyl)-6- (1,3-thiazol-5-yl)-1H-indol-2-yl]-7- methoxy-1-methyl-1H-1,3-benzodiazole-5- carbonyl}-2-azabicyclo[2.2.1]heptan-7- amine 553.5 1 1.61 274. (1R,4R,7R)-2-{2-[1-(cyclopropylmethyl)-6- (3-fluoro-4-methoxyphenyl)-1H-indol-2-yl]- 7-methoxy-1-methyl-1H-1,3-benzodiazole- 5-carbonyl}-2-azabicyclo[2.2.1]heptan-7- amine 594.2 2 1.64 275. 0 (1R,4R,7R)-2-{2-[6-(2-chloro-4- methoxyphenyl)-1-(cyclopropylmethyl)-1H- indol-2-yl]-7-methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2,2.1]heptan-7-amine 610.4 1 2.15 276. (1R,4R,7R)-2-{2-[1-(cyclopropylmethyl)-6- (3,5-difluoro-4-methoxyphenyl)-1H-indol-2- yl]-7-methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 612.5 1 2.14 277. (1R,4R,7R)-2-{2-[1-(cyclopropylmethyl)-6- (3,4,5-trifluorophenyl)-1H-pyrrolo[2,3- bipyridin-2-yl]-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 601.4 1 2.23 278. (1R,4R,7R)-2-{2-[1-(cyclopropylmethyl)-6- (4-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin- 2-yl]-7-methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 565.1 1 2.12 279. (1R,4R,7R)-2-{2-[1-(cyclopropylmethyl)-6- (4-fluoro-3-methoxyphenyl)-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 595.4 1 2.15 280. (1R,4R,7R)-2-{2-[1-(cyclopropylmethyl)-6- (3,4,5-trifluorophenyl)-1H-indol-2-yl]-7- methoxy-1-methyl-1H-1,3-benzodiazole-5- carbonyl}-2-azabicyclo[2,2.1]heptan-7- amine 600.4 2 1.84 281. (1R,4R,7R)-2-{2-[1-(cyclopropylmethyl)-6- (4-fluorophenyl)-1H-indol-2-yl]-7-methoxy- 1-methyl-1H-1,3-benzodiazole-5-carbonyl}- 2-azabicyclo[2.2.1]heptan-7-amine 564.1 2 1.83 282. (1R,4R,7R)-2-{2-[6-(4-chloro-3- fluorophenyl)-1-(cyclopropylmethyl)-1H- indol-2-yl]-7-methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 598.4 1 2.29 283. (1R,4R,7R)-2-{2-[1-(cyclopropylmethyl)-6- (4-fluoro-3-methoxyphenyl)-1H-indol-2-yl]- 7-methoxy-1-methyl-1H-1,3-benzodiazole- 5-carbonyl}-2-azabicyclo[2.2.1]heptan-7- amine 594.3 2 1.58 284. 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-fluorobenzoic acid 609 1 1.14 285. 0 3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2.3- b]pyridin-6-yl)-2,6-difluorobenzoic acid 627.1 1 1.22 286. 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 2-fluorobenzoic acid 608.2 1 1.41 287. 3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 2,6-difluorobenzoic acid 626 2 1.48 288. 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 2-chlorobenzoic acid 624.3 2 1.57 289. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3-dihydro-1H-indol-2-one 608.5 1 1.34 290. 2′-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodinzol-2- yl}-1′-(cyclopropylmethyl)-2,3-dihydro- 1H,1′H-[5,6′-biindole]-2-one 601.5 2 1.25 291. [3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)phenyl]methanol 576 1 1.81 292. [3-(2-{5-(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 4-fluorophenyl]methanol 594.5 1 1.59 293. [3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 2-fluorophenyl]methanol 594.6 2 1.49 294. [5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 2-methoxyphenyl]methanol 606.6 2 1.52 295. 0 N-[3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)phenyl]acetamide 603.3 1 1.78 296. [3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4-fluorophenyl]methanol 595.4 1 1.57 297. [3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2.3- b]pyridin-6-yl)-2-fluorophenyl]methanol 595.3 2 1.35 298. [5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-methoxyphenyl]methanol 607.1 2 1.39

(360) TABLE-US-00007 TABLE 7 Cmpd# Structure Name Obs. MS Ion HPLC Method IDs RT (min) 299. N-[3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6- yl)phenyl]acetamide 604.1 1 1.34 300. 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-2- acetamidobenzoic acid 648.2 1 1.34 301. 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 2-acetamidobenzoic acid 647.5 2 1.24 302. methyl N-[4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy- 1-methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]carbamate 626.2 2 1.64 303. 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-2-fluorophenol 581.1 2 1.76 304. methyl N-[4-(2-{5-[(1R,4R,7R)-7-amino- 2-azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)pyridin-2- yl]carbamate 621.4 2 1.62 305. 00 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-2,4- difluorophenol 599.3 1 1.62 306. 01 3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-4-fluorophenol 581.1 1 1.56 307. 02 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 2-fluorophenol 580.4 2 1.73 308. 03 methyl N-[4-(2-{5-[(1R,4R,7R)-7-amino- 2-azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)pyridin-2-yl]carbamate 620.5 1 1.15 309. 04 3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 4-fluorophenol 580.5 1 1.47 310. 05 N-{[3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)phenyl]methyl}acetamide 617.5 2 1.58 311. 06 3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 2-fluorophenol 580.4 2 1.7 312. 07 3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 5-fluorophenol 580.2 2 1.86 313. 08 2-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 6-fluorophenol 580.2 2 1.88 314. 09 N-{[3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6- yl)phenyl]methyl}acetamide 617.9 2 1.74 315. 0 3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-2-fluorophenol 581.3 2 1.72 316. (1R,4R,7R)-2-{2-[1-(cyclopropylmethyl)- 6-(2,3-difluoropyridin-4-yl)-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 2-azabicyclo[2.2.1]heptan-7-amine 584.4 1 1.63 317. N-{[3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6- yl)phenyl]methyl}methanesulfonamide 654.1 2 1.79 318. methyl 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-1H-indole-2- carboxylate 644 1 1.73 319. ethyl 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-1H-1,3- benzodiazole-2-carboxylate 659.4 1 1.42 320. 7-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-1,2,3,4- tetrahydroisoquinolin-1-one 616.2 1 1.45 321. 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-7-fluoro-2,3- dihydro-1H-indol-2-one 620 2 1.69 322. ethyl 5-(2-{[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 1H-1,3-benzodiazole-2-carboxylate 658 2 1.77 323. 7-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 1,2,3,4-tetrahydroisoquinolin-1-one 615 1 1.48 324. 2′-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1′-(cyclopropylmethyl)-7-fluoro-2,3- dihydro-1H,1′H-[5,6′-biindole]-2-one 618.9 1 1.44 325. 0 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-4-hydroxy- 1,2-dihydroquinolin-2-one 630 2 1.48 326. 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)quinolin-4-ol 613.92, 613.96 2 327. methyl 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-4- hydroxyquinoline-2-carboxylate 672.2 2 1.58 328. methyl 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-1- benzothiophene-2-carboxylate 661 1 2.02 329. 7-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-2,3-dihydro- 1H-indol-2-one 602.2 1 1.61 330. 7-(2-{-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)naphthalen-2-ol 613.3 2 1.87 331. 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 4-hydroxy-1,2-dihydroquinolin-2-one 629.2 1 1.22 332. 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)quinolin-4-ol 613.2 2 1.56 333. methyl 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-4- hydroxynaphthalene-2-carboxylate 671.1 2 1.49 334. 2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-2′,3′-dihydro- 1H,1′H-[6,7′-biindole]-2′-one 601 1 1.48 335. 0 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-2- fluorobenzamide 608.3 2 1.5 336. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)benzene-1- sulfonamide 626.2 1 1.37 337. 2-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)benzamide 590.3 2 1.4 338. (1R,4R,7R)-2-{2-[1-(cyclopropylmethyl)- 6-(quinolin-6-yl)-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 598.1 2 1.68 339. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 2-fluorobenzamide 607.2 2 1.49 340. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 2-chlorobenzamide 623.3 2 1.48 341. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropymethyl)-1H-indol-6- yl)benzene-1-sulfonamide 625.2 2 1.42 342. 2-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)benzamide 589.2 1 1.25 343. (1R,4R,7R)-2-{2-[1-(cyclopropylmethyl)- 6-(quinolin-6-yl)-1H-indol-2-yl]-7- methoxy-1-methyl-1H-1,3-benzodiazole- 5-carbonyl}-2-azabicyclo[2.2.1]heptan-7- amine 597.3 1 1.13 344. 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3-dihydro-1H-isoindol- 1-one 572.1 2 1.28 345. 0 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3-dihydro-1H-indol-2- one 571.9 2 1.39 346. 6-(2-{-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-1-methyl- 1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2,3,4-tetrahydroquinolin- 2-one 592.1 1 1.32 347. 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-1-methyl- 1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3-dihydro-1H-isoindol- 1-one 578.1 2 1.42

(361) TABLE-US-00008 TABLE 8 Cmpd # Structure Name Obs. MS Ion HPLC Method IDs RT (min) 348. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-1-methyl- 1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3-dihydro-1H-indol-2- one 578.1 1 1.43 349. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)benzamide 560.2 2 1.2 350. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-1-methyl- 1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)benzamide 566.2 1 1.28 351. methyl N-[5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-1-methyl- 1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridin-2-yl]carbamate 597.3 1 1.43 352. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,6-difluorophenol 569.2 2 1.46 353. methyl N-[5-(2-{5-[(1R,4R,7R)-7-amino- 2-azabicyclo[2.2.1]heptane-2-carbonyl]- 1-methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridin-2-yl]carbamate 591.3 1 1.47 354. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)-2-methoxyphenyl acetate 634.3 2 1.69 355. 0 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropymethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-2- methoxyphenyl acetate 635 1 2.04 356 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-3- fluorobenzamide 608.2 1 1.4 357. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)-3-fluorobenzamide 607.4 1 1.42 358. 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)pyridine-2-carboxamide 589.9 2 1.36 359 (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(quinolin-5-yl)- 1H-pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 5-carbonyl}-2-azabicyclo[2.2.1]heptan-7- amine 598.2 1 1.7 360. (1R,4R,7R)-2-{2-[1- (cyclopropyljmethyl)-6-(2- methylquinolin-5-yl)-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 612 2 1.31 361. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-[4-(1H-1,2,3,4- tetrazol-5-yl)phenyl]-1H-pyrrolo[2,3- b]pyridin-2-yl}-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 615 1 1.36 362. (1R,4R,7R)-2-{2-[1- (cyclopropylmetnyl)-6-(quinolin-5-yl)- 1H-indol-2-yl]-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 597.2 2 1.32 363. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(2- methylquinolin-5-yl)-1H-indol-2-yl]-7- methoxy-1-methyl-1H-1,3-benzodiazole- 5-carbonyl}-2-azabicyclo[2.2.1]heptan-7- amine 611.3 2 1.23 364. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-3- methoxybenzamide 310.6 2 1.34 365. 0 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)quinolin-1- ium-1-olate 614.1 1 1.56 366. 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-4- hydroxyquinoline-3-carboxylic acid 658.3, 658.17, 658.31 1 367. 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-8-fluoro- 1,2,3,4-tetrahydroquinolin-2-one 634.2 1 1.68 368. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)-3-methoxybenzamide 619.4 1 1.54 369. 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)quinolin-1-ium-1-olate 613.2 1 1.57 370. 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)-4-hydroxyquinoline-3-carboxylic acid 657.3 2 1.41 371. 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)-8-fluoro-1,2,3,4-tetrahydroquinolin-2- one 633.4 2 1.39 372. 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)quinoline-2-carbonitrile 622.3 2 1.79 373. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)-2-hydroxybenzamide 605.3 2 1.43 374. 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)quinoline-2- carbonitrile 623.4 1 1.99 375. 0 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-2- hydroxybenzamide 606.3 2 1.34 376. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-2-chloro-6- methoxyphenol 627.3 1 1.83 377. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-3- fluorophenol 581.4 1 1.55 378. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-N- methylbenzene-1-sulfonamide 640.4 1 1.71 379. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(quinoxalin-6-yl)- 1H-pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3-benzodiazole- 5-carbonyl}-2-azabicyclo[2.2.1]heptan-7- amine 598.9 2 1.55 380. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-N- cyclopropylbenzene-1-sulfonamide 666.2 1 1.89 381. methyl N-[5-(2-{5-[(2S,5R)-5-amino-2- methylpiperidine-1-carbonyl]-7-methoxy- 1-methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridin-2-yl}carbamate 623 1 1.59 382. 4-(2-{5-[(2S,5R)-5-amino-2- methylpiperidine-1-carbonyl]-7-methoxy- 1-methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-fluorobenzamide 610.3 2 1.36 383. 4-(2-{5-[(2S,5R)-5-amino-2- methylpiperidine-1-carbonyl]-7-methoxy- 1-methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-chlorobenzamide 626.2 2 1.36 384. 6-(2-{5-[(2S,5R)-5-amino-2- methylpiperidine-1-carbonyl]-7-methoxy- 1-methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2-dihydroisoquinolin-1- one 616.2 1 1.51 385. 0 5-(2-{5-[(2S,5R)-5-amino-2- methylpiperidine-1-carbonyl]-7-methoxy- 1-methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3-dihydro-1H-indol-2- one 604.4 1 1.49 386. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-2,6- difluorobenzamide 626.4 1 1.49 387. 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)quinazolin-4- ol 615.3 2 1.3 388. 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)quinoxalin-2- ol 615.3 2 1.24 389. methyl 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)quinoline-2- carboxylate 656.37, 656.37 1 1 390. 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)quinoxalin-2-ol 614.2 1 1.49 391. 5-(2-(5-((1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl)-7- methoxy-1-methyl-1H-benzo[d]imidazol- 2-yl)-1-(cyclopropylmethyl)-1H-indol-6- yl)benzo[d]isothiazol-3(2H)-one 1,1- dioxide 651.3 2 1.26 392. methyl 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)quinoline-2-carboxylate 655.4 2 1.57 393. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)-2,6-difluorobenzamide 625.3 1 1.55 394. 2′-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1′-(cyclopropylmethyl)-3,3- difluoro-2,3-dihydro-1H,1′H-[5,6′- biindole]-2-one 637.3 2 1.56 395. 0 6-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)cinnolin-4-ol 613.9 2 1.35 396. 2′-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-4-chloro-1′-(cyclopropylmethyl)- 2,3-dihydro-1H,1′H-[5,6′-biindole]-2-one 635.2 2 1.37

(362) TABLE-US-00009 TABLE 9 Obs. HPLC Cmpd MS Method RT # Structure Name Ion IDs (min) 397. 2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol- 2-yl}-1- (cyclopropylmethyl)-N- [(oxolan-3-yl)methyl]- 1H-indole-6-carboxamide 597.2 1 1.28 398. 2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl- 1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-N-[(1,1- dioxidotetrahydrothiophen-3- yl)methyl]-1H-indole-6- carboxamide 645.1 1 1.21 399. 2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)- N-[(pyridin-4-yl)methyl]-1H- indol-6-amine 576.3 1 1.3 400. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6- (pyridin-4-yloxy)-1H-pyrrolo [2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}- 2-azabicyclo[2.2.1]heptan-7- amine 564.3 2 1 401. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-[(2,6- dimethylpyridin-4-yl)oxy]- 1H-pyrrolo[2,3-b]pyridin- 2-yl]-7-methoxy-1-methyl- 1H-1,3-benzodiazole-5- carbonyl}-2-azabicyclo [2.2.1]heptan-7-amine 592.3 1 1.75 402 (1R,4R,7R)-2-(2-[1- (cyclopropylmethyl)-6- [(pyridin-3-yl)amino]-1H- pyrrolo[2,3-b]pyridin-2- yl]-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl}- 2-azabicyclo[22.1]heptan-7- amine 563.2 1 1.48 403. N-{5-[(2-{5-[(1R,4R,7R)-7- amino-2-azabicyclo[2.2.1] heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6- yl)amino]pyridin-2-yl} acetamide 620.2 1 1.43 404. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6- (pyridine-4-sulfonyl)-1H- indol-2-yl]-7-methoxy-1- methyl-1H-l,3-benzodiazole- 5-carbonyl}-2-azabicyclo [2.2.1]heptan-7-amine 611.4 1 1.45 405. 00 (1R,4R,7R)-2-{2-[6-(azetidin- 3-yl)-1-(cyclopropylmethyl)- 1H-indol-2-yl]-7-methoxy- 1-methyl-1H-1,3- benzodiazole- 5-carbonyl}-2-azabicyclo [2.2.1]heptan-7-amine 525.2 1 1.04 406. 01 1-[3-(2-{5-[(1R,4R,7R)-7- amino-2-azabicyclo[2.2.1] heptane-2-carbonyl]-7- methoxy-1-methyl- 1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)- 1H-indol-6-yl)azetidin-1- yl]ethan-1-one 567.4 1 1.33

(363) TABLE-US-00010 TABLE 10 HPLC RT Cmpd # Structure Name Obs. MS Ion Method IDs (min) 407. 02 (1R,4R,7R)-2-[2-(6-{[4- (aminomethyl)phenyl]amino}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3-b] pyridin-2-yl)-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl]-2- azabicyclo[2.2.1]heptan-7-amine 591.4 1 1.18 408. 03 3-[(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6- yl)amino]benzamide 605.4 1 1.34 409. 04 (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-{[(pyridin-4- yl)methyl]amino}-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 577.4 1 1.42 410. 05 N-(3-{[(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6- yl)amino]methyl}phenyl)acetamide 633.5 2 1.17 411. 06 (1R,4R,7R)-2-[2-(6-{[3- (aminomethyl)phenyl]amino}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-2-yl)-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl]-2- azabicyclo[2.2.1]heptan-7-amine 591.2 2 1.11 412. 07 4-[(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6- yl)amino]piperidin-2-one 583.4 1 1.01 413. 08 4-[(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6- yl)amino]piperidin-2-one 583 1 1.3  414. 09 (1R,4R,7R)-2-{2-[6-cyclohexyl-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 553.4 1 2.33 415. 0 (1R,4R,7R)-2-{2-[6-cyclopropyl-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl}-2- azabicyclo[22.1]heptan-7-amine 511.2 2 1.4  416. (1R,4R,7R)-2-{2-[6-cyclopentyl-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 539.4 1 2.25 417. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(2- ethoxypyrimidin-5-yl)-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 593.4 1 1.74 418. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-[(oxolan-3- yl)methyl]-1H-pyrrolo[2,3-b]pyridin-2- yl]-7-methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 555.5 1 1.6  419. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(oxetan-3-yl)-1H- indol-2-yl]-7-methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 526.1 2 1.36 420. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(piperidin-4-yl)- 1H-indol-2-yl]-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 553.5 2 0.95 421. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(pyrrolidin-3-yl)- 1H-pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3-benzodiazole- 5-carbonyl}-2-azabicyclo[2.2.1]heptan-7- amine 539.9 2 1.08 422. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(pyrrolidin-3-yl)- 1H-indol-2-yl]-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 539.2 1 1.31 423. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-[(piperidin-4- yl)methyl]-1H-indol-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5- carbonyl}-2-azabicyclo[2.2.1]heptan-7- amine 567.6 2 1.05 424. 1-[4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)piperidin-1-yl]ethan-1-one 595.5 1 1.53 425. 0 3-[2-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)ethyl]-1.3-oxazolidin-2-one 583.4 1 1.45 426. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(piperidin-4-yl)- 1H-pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3-benzodiazole- 5-carbonyl}-2-azabicyclo[2.2.1]heptan-7- amine 554.3 1 1.26 427. benzyl 3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)pyrrolidine-1- carboxylate  674.15, 674.08 2  1.67, 1.72 428. benzyl 3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)pyrrolidine-1-carboxylate  673.24, 673.26 1 1.86 429. 1-[3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)pyrrolidin-1-yl]ethan-1-one 581.6 2 1.2 430. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(1-methyl-1H- 1,2,3-benzotriazol-6-yl)-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 602.4 2 1.37 431. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-(1-methyl-1H- 1,2,3-benzotriazol-6-yl)-1H-indol-2-yl]- 7-methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 601.2 2 1.6 432. 5-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)-2,3-dihydro-1,3-benzoxazol-2-one 603.1 1 1.61 433. 3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)cyclobutan-1-ol 540.1 2 1.19 434. 3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)cyclobutan-1-ol 540.4 2 1.29 435. 0 (1r,3r)-3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)cyclobutan-1-ol 541.0 3 0.66 436. (1s,3s)-3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)cyclobutan-1-ol 541.0 3 0.65 437. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-{[(2R)-oxan-2- yl]methyl}-1H-pyrrolo[2,3-b]pyridin-2- yl]-7-methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 569.3 1 1.68 438. (1R,4R,7R)-2-{2-[1- (cyclopropylmethyl)-6-{[(2R)-oxan-2- yl]methyl}-1H-pyrrolo[2,3-b]pyridin-2- yl]-7-methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 569.2 1 1.77 439. methyl 3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)cyclobutane- 1-carboxylate 583.4 2 1.49 440. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)cyclohexan-1-ol 569.3 2 1.26 441. methyl (1s,3s)-3-(2-{5-[(1R,4R,7R)-7- amino-2-azabicyclo[2.2.1]heptane-2- carbonyl]-7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)cyclobutane-1-carboxylate 583.4 2 1.51 442. 3-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-1- methylcyclobutan-1-ol 555.2 2 1.23 443. 1-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)-2-methylpropan-2-ol 542.4 1 1.48 444. 4-(2-{5-[(1R,4R,7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol- 2-yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)cyclohexan-1-ol 568.2 2 1.4

(364) Other examples with experimental details are shown below for Examples 445-448.

Example 445

((3R,5R)-3-amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-(1,1-difluoroethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-5-yl)methanone

(365) ##STR00640##

Example 445

Step A: methyl 2-(6-acetyl-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate

(366) ##STR00641##

Example 445A

(367) A mixture of methyl 2-(6-chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (890 mg, 2.095 mmol) [for this starting material see: WO 2017/0100594)], 1-ethoxyvinyltri-n-butyltin (0.856 mL, 2.51 mmol), xantphos (364 mg, 0.628 mmol) and Pd.sub.2(dba).sub.3 (192 mg, 0.209 mmol) in degassed dioxane (10 mL) under nitrogen was stirred at 100° C. for 18 hours. The mixture cooled to rt. A solution of 1.0 M aqueous HCl (2.095 mL, 2.095 mmol) was added and the mixture was stirred at RT for 1 hours. The mixture was diluted with EtOAc (15 mL) and was washed with a solution of aqueous saturated sodium bicarbonate (2×15 mL). The organic layer was dried over sodium sulfate and concentrated. The resulting residue was subjected to ISCO flash chromatography (silica gel/hexane-EtOAc 100:0 to 0:100 gradient) to yield methyl 2-(6-acetyl-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate 445A (850 mg, 1.769 mmol, 84% yield) as light brown solid: LCMS (M+H)=433.4, retention time=1.06 min (Method 3).

Step B: methyl (E)-2-(1-(cyclopropylmethyl)-6-(1-(hydroxyimino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate

(368) ##STR00642##

Example 445B

(369) A mixture of methyl 2-(6-acetyl-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate 445A (400 mg, 0.925 mmol), hydroxylamine hydrochloride (70.7 mg, 1.017 mmol) in MeOH (12 mL) was stirred at 60° C. for 3 hours (J. Med. Chem. 2012, 55, 3364). The mixture was concentrated. The mixture was diluted with EtOAc (15 mL) and was washed with a solution of aqueous saturated sodium bicarbonate (2×15 mL). The organic layer was dried over sodium sulfate and concentrated to give crude methyl (E)-2-(1-(cyclopropylmethyl)-6-(1-(hydroxyimino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate 445B as off-white solid: LCMS (M+H)=448.5, retention time=0.95 min (Method 3), which was taken to next step.

Step C: methyl 2-(1-(cyclopropylmethyl)-6-(1,1-difluoroethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate

(370) ##STR00643##

Example 445C

(371) To a solution of methyl (E)-2-(1-(cyclopropylmethyl)-6-(1-(hydroxyimino)ethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate 445B from above in DCM (5.0 mL) in a capped syringe tube at −78° C. under nitrogen was added 70% HF-pyridine (1310 mg, 9.25 mmol), the mixture was stirred at −78° C. for 15 min. A solution of tert-butyl nitrite (286 mg, 2.77 mmol) in DCM (5.0 mL) was added dropwise to the mixture, the reaction was stirred at −78° C. for 30 min. and rt for 1 hour. The mixture was then added to sulfuric acid (1.0 mL) and ice water (200 g) and the mixture was stirred at rt for 30 min. The organic layer was collected and was washed with a solution of aqueous saturated sodium bicarbonate (35 mL). The organic layer was dried over sodium sulfate and concentrated. The resulting residue was subjected to ISCO flash chromatography (silica gel/hexane-EtOAc 100:0 to 50:50 gradient) to give methyl 2-(1-(cyclopropylmethyl)-6-(1,1-difluoroethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate (92 mg, 0.192 mmol, 20.79% yield) 445C as white solid: .sup.1H NMR (499 MHz, chloroform-d) δ 8.23 (d, J=1.2 Hz, 1H), 8.09 (d, J=8.1 Hz, 1H), 7.56 (d, J=8.1 Hz, 1H), 7.52-7.47 (m, 1H), 6.84 (s, 1H), 4.55 (d, J=7.2 Hz, 2H), 4.18 (s, 3H), 4.09-4.06 (m, 3H), 3.99 (s, 3H), 2.16 (t, J=18.5 Hz, 3H), 1.22-1.12 (m, 1H), 0.39-0.31 (m, 2H), 0.23-0.17 (m, 2H); LCMS (M+H)=455.4, retention time=1.09 min (Method 3).

Step D: 2-(1-(cyclopropylmethyl)-6-(1,1-difluoroethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylic acid

(372) ##STR00644##

Example 445D

(373) A mixture of methyl 2-(1-(cyclopropylmethyl)-6-(1,1-difluoroethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylate 445C (102 mg, 0.224 mmol) and 2.0 M aqueous lithium hydroxide (561 μl, 1.122 mmol) in THF (5.0 mL) was stirred at 50° C. for 18 hours. A solution of 1.0 M aqueous HCl (1.20 mL) was added and the mixture was concentrated. The mixture was extracted with EtOAc (2×15 mL) and the ethyl acetate layer was dried over sodium sulfate and concentrated to give crude 2-(1-(cyclopropylmethyl)-6-(1,1-difluoroethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylic acid 445D (101 mg, 0.218 mmol, 97% yield) as white solid: LCMS (M+H)=441.4, retention time=0.96 min (Method 3).

Example 445: ((3R,5R)-3-amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-(1,1-difluoroethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-5-yl)methanone

(374) ##STR00645##

Example 445

(375) A mixture of 2-(1-(cyclopropylmethyl)-6-(1,1-difluoroethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carboxylic acid 445D (20 mg, 0.045 mmol), tert-butyl ((3R,5R)-5-fluoropiperidin-3-yl)carbamate (9.91 mg, 0.045 mmol), BOP (22.09 mg, 0.050 mmol) and TEA (31.6 μl, 0.227 mmol) in DMF (1.0 mL) was stirred at rt for 2 hours. The mixture was diluted with EtOAc (5 mL) and was washed with a solution of aqueous saturated sodium bicarbonate (2×5 mL). The organic layer was dried over sodium sulfate and concentrated to give crude tert-butyl ((3R,5R)-1-(2-(1-(cyclopropylmethyl)-6-(1,1-difluoroethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carbonyl)-5-fluoropiperidin-3-yl)carbamate: LCMS (M+H)=641.6, retention time=1.00 min (Method 3), which was taken to next step. A mixture of tert-butyl ((3R,5R)-1-(2-(1-(cyclopropylmethyl)-6-(1,1-difluoroethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carbonyl)-5-fluoropiperidin-3-yl)carbamate in DCM (1.0 mL) and TFA (1.0 mL) was stirred at rt for 30 min. The mixture was concentrated. The resulting residue was purified by prep-HPLC (Phenomenex, Luna 5 micron 30×250 mm, flow rate=30 ml/min., gradient=20% A to 100% B in 30 min., A=H2O/ACN/TFA(90:10:0.1), B=H2O/ACN/TFA (10:90:0.1)). The pure product fraction was loaded onto Strata-X-C 33 um cation mixed-mode polymer cartridge (0.30 g), the cartridge was washed with methanol (20 ml) and the product was eluted with 0.5 N NH.sub.3 in methanol (5.0 mL). The NH.sub.3 eluent was concentrated and the pure product was lyophilized with ACN/H2O (1:1, 10 mL) to yield ((3R,5R)-3-amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-(1,1-difluoroethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-5-yl)methanone 445 (16.90 mg, 0.031 mmol, 67.5% yield) as white powder: .sup.1H NMR (499 MHz, METHANOL-d.sub.4) δ 8.22 (d, J=8.1 Hz, 1H), 7.55 (d, J=8.2 Hz, 1H), 7.44 (s, 1H), 7.05 (s, 1H), 7.02-6.95 (m, 1H), 4.82-4.64 (m, 1H), 4.48 (d, J=7.2 Hz, 2H), 4.06 (s, 7H), 3.43-3.35 (m, 2H), 3.26-3.06 (m, 1H), 3.01-2.53 (m, 1H), 2.45-2.28 (m, 11H), 2.12 (t, J=18.5 Hz, 3H), 1.72-1.50 (m, 11H), 1.05-0.97 (m, 1H), 0.38-0.30 (m, 2H), 0.14-0.04 (m, 2H); LCMS (M+H)=541.5, retention time=0.83 min (Method 3).

Example 446

((3R,5R)-3-amino-5-fluoropiperidin-1-yl)(2-(6-(1-cyclobutyl-1-hydroxyethyl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-5-yl)methanone

(376) ##STR00646##

Example 446

Step A: tert-butyl ((3R,5R)-1-(2-(6-acetyl-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carbonyl)-5-fluoropiperidin-3-yl)carbamate

(377) ##STR00647##

Example 446A

(378) tert-butyl ((3R,5R)-1-(2-(6-acetyl-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carbonyl)-5-fluoropiperidin-3-yl)carbamate was prepared using the procedure of example 445, step A, but starting with tert-butyl ((3R,5R)-1-(2-(6-chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carbonyl)-5-fluoropiperidin-3-yl)carbamate to give tert-butyl ((3R,5R)-1-(2-(6-acetyl-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carbonyl)-5-fluoropiperidin-3-yl)carbamate 446A: LCMS (M+H)=619.4, retention time=0.89 min (Method 3).

Example 446: ((3R,5R)-3-amino-5-fluoropiperidin-1-yl)(2-(6-(1-cyclobutyl-1-hydroxyethyl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-5-yl)methanone

(379) ##STR00648##

Example 446

(380) To a solution of tert-butyl ((3R,5R)-1-(2-(6-acetyl-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carbonyl)-5-fluoropiperidin-3-yl)carbamate 446A (20 mg, 0.032 mmol) in THF (1.0 mL) was added a solution of 0.5 M cyclobutylmagnesium bromide in 2-methyltetrahydrofuran (194 μl, 0.097 mmol), the mixture was stirred at rt for 60 min. The mixture was added to a solution of 10% aqueous ammonium chloride solution (10 mL). The mixture was extracted with EtOAc (15 mL). The organic layer was dried over sodium sulfate and concentrated to give crude tert-butyl ((3R,5R)-1-(2-(6-(1-cyclobutyl-1-hydroxyethyl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carbonyl)-5-fluoropiperidin-3-yl)carbamate: LCMS (M+H)=675.4, retention time=0.94 min (Method 3), which was taken to next step.

(381) A mixture of tert-butyl ((3R,5R)-1-(2-(6-(1-cyclobutyl-1-hydroxyethyl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carbonyl)-5-fluoropiperidin-3-yl)carbamate in DCM (1.0 mL) and TFA (0.40 mL) was stirred at rt for 30 min. The mixture was concentrated. The resulting residue was purified by prep-HPLC (Phenomenex, Luna 5 micron 30×250 mm, flow rate=30 ml/min., gradient=20% A to 100% B in 30 min., A=H2O/ACN/TFA(90:10:0.1), B=H2O/ACN/TFA(10:90:0.1)). The pure product fraction was loaded onto Strata-X-C 33 um cation mixed-mode polymer cartridge (0.30 g), the cartridge was washed with methanol (20 ml) and the product was then eluted with 0.5 N NH.sub.3 in methanol (5.0 mL). The NH.sub.3 eluent was concentrated and the product was lyophilized with ACN/H2O (1:1, 5 mL) to give ((3R,5R)-3-amino-5-fluoropiperidin-1-yl)(2-(6-(1-cyclobutyl-1-hydroxyethyl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-5-yl)methanone 446 (8.19 mg, 0.014 mmol, 41.9% yield) as white powder: .sup.1H NMR (499 MHz, methanol-d.sub.4) δ 8.08 (d, J=8.2 Hz, 1H), 7.41 (d, J=8.3 Hz, 2H), 6.99-6.95 (m, 2H), 4.83-4.63 (m, 1H), 4.48 (br s, 2H), 4.26-3.96 (m, 7H), 3.47-3.35 (m, 1H), 3.24-3.15 (m, 1H), 3.03-2.92 (m, 1H), 2.79-2.53 (m, 1H), 2.46-2.14 (m, 2H), 2.05-1.93 (m, 2H), 1.88-1.75 (m, 1H), 1.74-1.46 (m, 7H), 1.03-0.91 (m, 1H), 0.33 (br d, J=8.1 Hz, 2H), 0.07 (br d, J=4.1 Hz, 2H); LCMS (M+H)=575.4, retention time=0.91 min (Method 3).

Example 447

((3R,5R)-3-amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-(1,3-difluoro-2-hydroxypropan-2-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-5-yl)methanone

(382) ##STR00649##

Example 447

Step A: tert-butyl ((3R,5R)-1-(2-(1-(cyclopropylmethyl)-6-(1,3-difluoro-2-hydroxypropan-2-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carbonyl)-5-fluoropiperidin-3-yl)carbamate

(383) ##STR00650##

Example 447A

(384) To a solution of tert-butyl ((3R,5R)-1-(2-(6-bromo-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carbonyl)-5-fluoropiperidin-3-yl)carbamate (85 mg, 0.130 mmol) [made in a similar fashion to Intermediate 2 but starting with ethyl 6-bromo-1H-pyrrolo[2,3-b]pyridine-2-carboxylate] in anhydrous ethyl ether (10 mL) and anhydrous THF (3.0 mL) under nitrogen at −78° C. was added a solution of 1.60 M n-butyllithium in hexane (203 μl, 0.324 mmol), the mixture was stirred at −78° C. for 30 min. 1,3-difluoropropan-2-one (14.63 mg, 0.156 mmol) was then added to the mixture at −78° C., the mixture was stirred at −78° C. for 10 min and rt for 1 hours. The mixture was diluted with EtOAc (15 mL) and was washed with a solution of aqueous saturated sodium bicarbonate (2×15 mL). The organic layer was dried over sodium sulfate and concentrated. The resulting residue was subjected to ISCO flash chromatography (silica gel/hexane-5% MeOH/EtOAc 100:0 to 0:100 gradient) to give tert-butyl ((3R,5R)-1-(2-(1-(cyclopropylmethyl)-6-(1,3-difluoro-2-hydroxypropan-2-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carbonyl)-5-fluoropiperidin-3-yl)carbamate 447A (35 mg, 0.052 mmol, 40.2% yield): LCMS (M+H)=671.5, retention time=0.86 min (Method 3).

Example 447: ((3R,5R)-3-amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-(1,3-difluoro-2-hydroxypropan-2-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-5-yl)methanone

(385) ##STR00651##

Example 447

(386) A mixture of tert-butyl ((3R,5R)-1-(2-(1-(cyclopropylmethyl)-6-(1,3-difluoro-2-hydroxypropan-2-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carbonyl)-5-fluoropiperidin-3-yl)carbamate 447A (35 mg, 0.052 mmol, 40.2% yield) in DCM (1.0 mL) and TFA (1.0 mL) was stirred at rt for 30 min. The solution was concentrated and the resulting residue was purified by prep-HPLC (Phenomenex, Luna 5 micron 30×250 mm, flow rate=30 ml/min., gradient=20% A to 100% B in 30 min., A=H2O/ACN/TFA(90:10:0.1), B=H2O/ACN/TFA(10:90:0.1)). The pure product fraction was loaded onto Strata-X-C 33 um cation mixed-mode polymer cartridge (0.30 g), the cartridge was washed with methanol (20 ml) and then the product was eluted with 0.5 N NH.sub.3 in methanol (5.0 mL). The product NH.sub.3 eluent was concentrated and the product was lyophilized with ACN/H2O (1:1, 5 mL) to give ((3R,5R)-3-amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-(1,3-difluoro-2-hydroxypropan-2-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-5-yl)methanone 447 (16.30 mg, 0.029 mmol, 22.03% yield): .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 7.97 (d, J=8.2 Hz, 1H), 7.36 (d, J=8.2 Hz, 1H), 7.13 (s, 1H), 6.87 (s, 1H), 6.66 (s, 1H), 4.92-4.48 (m, 6H), 4.44-4.17 (m, 3H), 4.01-3.62 (m, 6H), 2.79-2.43 (m, 2H), 2.04-1.88 (m, 1H), 1.47-1.16 (m, 1H), 1.08-0.87 (m, 2H), 0.19-0.10 (m, 4H); LCMS (M+H)=571.3, retention time=1.39 min (Method 2).

Example 448

2-(4-(2-(5-((1R,4R,7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)phenoxy)acetamide

(387) ##STR00652##

Example 448

(388) A mixture of of ((1R,4R,7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(6-chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-5-yl)methanone (1.5 g, 2.495 mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (0.760 g, 2.99 mmol), and potassium acetate (0.612 g, 6.24 mmol) in dioxane (12 ml) in a 2 dr vial was sonicated and treated with 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (0.102 g, 0.125 mmol) and the vial was capped. This reaction mixture was made anaerobic by a pump/backfill with nitrogen cycle (5×). It was set to stir at 90° C. for 5 h and the starting material was found to be consumed. The reaction mixture was evaporated and dried in vacuo. The resulting brown solid was used or the next step. A portion of this material (45 mg, 0.047 mmol), 2-(4-bromophenoxy)acetamide (13.08 mg, 0.057 mmol), sodium carbonate, 2N in water (0.071 mL, 0.142 mmol) and 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (3.87 mg, 4.74 μmol) in DMF (1 mL). The vial was capped and the reaction mixture was made anaerobic by a pump/backfill with nitrogen cycle (5×). The reaction was stirred at 70° C. for overnight. After cooling to rt, the solution was diluted with DMF, filtered and purified via preparative LC/MS with the following conditions: Column: XBridge C18, 200 mm×19 mm, 5-μm particles; Mobile Phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid; Mobile Phase B: 95:5 acetonitrile:water with 0.1% trifluoroacetic acid; Gradient: a 0-minute hold at 11% B, 11-51% B over 20 minutes, then a 4-minute hold at 100% B; Flow Rate: 20 mL/min; Column Temperature: 25 C. Fraction collection was triggered by product MS signals. Fractions containing the desired product were combined and dried via centrifugal evaporation. The purified product was then diluted with DMF, treated with Si-Pyridine resin and shaken for a minimum of 2 h. The resulting mixture was filtered and dried via centrifugal evaporation to give 2-(4-(2-(5-((1R,4R,7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)phenoxy)acetamide 448 (20.6 mg): .sup.1H NMR (500 MHz, DMSO-d.sub.6) δ 8.17-8.13 (m, 3H), 7.95-7.92 (m, 1H), 7.78-7.74 (m, 1H), 7.62-7.53 (m, 2H), 7.44-7.40 (m, 1H), 7.11-7.08 (m, 2H), 7.08-7.06 (m, 1H), 7.02-6.94 (m, 1H), 4.57-4.52 (m, 2H), 4.52-4.50 (m, 2H), 4.18-4.12 (m, 3H), 4.03-3.95 (m, 3H), 3.83-3.71 (m, 1H), 3.66-3.54 (m, 1H), 3.53-3.44 (m, 1H), 3.22-3.15 (m, 1H), 2.69-2.57 (m, 1H), 2.02-1.85 (m, 3H), 1.74-1.59 (m, 1H), 1.28-1.11 (m, 2H), 0.35-0.29 (m, 2H), 0.20 (br s, 2H); LCMS (M+H)=620.0, retention time=1.58 min (Method 1).

(389) From the methods above, the following compounds were synthesized.

(390) TABLE-US-00011 HPLC Obs. Method # Structure Name MS Ion ID RT 449. 2-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)propan-2-ol 528.1 2 1.31 450. 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)quinazolin-4-ol 614.2 2 1.2 451. methyl 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 1H-pyrrolo[2,3-b]pyridine-3-carboxylate 644.2 1 1.62 452. 6-(2-(5-((7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl)-7- methoxy-1-methyl-1H-benzo[d]imidazol- 2-yl)-1-(cyclopropylmethyl)-1H-indol-6- yl)-1-methyl-1H-benzo[c][1,2]thiazin- 4(3H)-one 2,2-dioxide 679 1 1.76 453. 7-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)isoquinolin-2-ium-2-olate 613.1 1 1.43 454. 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3,3-difluoro-2,3-dihydro- 1H-indol-2-one 638.3 2 1.51 455. 6-(2-(5-((7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl)-7- methoxy-1-methyl-1H-benzo[d]imidazol- 2-yl)-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-1-methyl-1H- benzo[c][1,2]thiazin-4(3H)-one 2,2-dioxide 680.4 1 1.79 456. 0 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)cinnolin-4-ol 615.1 1 1.41 457. 7-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)isoquinolin-2-ium-2-olate 614.4 2 1.21 458. S-[3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]-2-hydroxyethane-1- sulfonamido 670.1 2 1.39 459. 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-chlorobenzamide 624.3 2 1.33 460. 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-fluorobenzamide 608.2 2 1.29 461. 4-[(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)amino]-2-methoxyphenol 608.1 2 1.21 462. 7-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)quinazolin-4-ol 615 2 1.29 463. 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-7-methoxy-1,2,3,4- tetrahydroquinolin-2-one 646.4 1 1.53 464. 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-7-hydroxy-1,2,3,4- tetrahydroquinolin-2-one 632.4 2 1.37 465. 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2-dihydroquinolin-2-one 614 1 1.56 466. 0 3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)benzene-1-sulfonamide 626.4 1 1.49 467. 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)-2,3- dihydro-1H-isoindol-1-one 606.9 1 1.62 468. 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 2,3-dihydro-1H-isoindol-1-one 601.5 2 1.3 469. 6-(2-{5-[(2S,5R)-5-amino-2- methylpiperidine-1-carbonyl]-7-methoxy- l-methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3-dihydro-1H-isoindol-1- one 604.4 1 1.44 470. 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- fluoro-1-methyl-1H-1,3-benzodiazol-2-yl}- l-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3-dihydro-1H-isoindol-1- one 590.4 2 1.33 471. 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3-dihydro-1H-isoindol-1- one 608.2 2 1.43 472. ethyl 7-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 4-hydroxyquinoline-3-carboxylate 685.2 2 1.45 473. 7-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)quinolin-4-ol 613.3 1 1.4 474. 7-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)quinolin-4-ol 614.1 1 1.35 475. 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 1,8-naphthyridin-2-ol 614.3 2 1.3 476. 0 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,8-naphthyridin-2-ol 615.4 2 1.19 477. 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)quinoline-2-carboxamide 641.5 2 1.43 478. 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 4-hydroxyquinoline-2-carboxylic acid 657.2 1 1.14 479. 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4-hydroxyquinoline-2- carboxylic acid 658.4 2 1.14 480. ((7R)-7-amino-2-azabicyclo[2.2.1]heptan- 2-yl)(2-(l-(cyclopropylmethyl)-6-(4- hydroxyquinolin-7-yl)-1H-pyrrolo[2,3- b]pyridin-2-yl)-7-methoxy-1-(methyl-d3)- 1H-benzo[d]imidazol-5-yl)methanone 617.4 2 1.15 481. 5-(2-(5-((7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl)-7- methoxy-1-(methyl-d3)-1H- benzo[d]imidazol-2-yl)-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)indolin-2-one 605.2 2 1.24 482. 6-(2-(5-((7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl)-7- methoxy-1-(methyl-d3)-1H- benzo[d]imidazol-2-yl)-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)isoindolin-1-one 605.4 2 1.24 483. 5-(2-(5-((7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl)-7- methoxy-1-(methyl-d3)-1H- benzo[d]imidazol-2-yl)-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)quinolin-2(1H)-one 617.4 1 1.55 484. 3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 5H,6H,7H-pyrrolo[3,4-b]pyridin-5-one 602.3 2 1.11 485. methyl (5-(2-(5-((7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl)-7- methoxy-1-(methyl-d3)-1H- benzo[d]imidazol-2-yl)-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridin-2-yl)carbamate 624.1 1 1.72 486. 0 methyl (4-(2-(5-((7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl)-7- methoxy-1-(methyl-d3)-1H- benzo[d]imidazol-2-yl)-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl)carbamate 623.4 1 1.81 487. methyl 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1H-pyrrole-2-carboxylate 594.2 2 1.67 488. methyl N-[6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridin-3-yl]carbamate 621.4 1 1.55 489. 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-hydroxy-3-methyl-2,3- dihydro-1H-indol-2-one 632.4 2 1.2 490. 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4-hydroxyquinoline-3- carbonitrile 639.2 1 1.48 491. ethyl 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 4-hydroxyquinoline-3-carboxylate 685.4 2 1.3 492. 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 4-hydroxyquinoline-3-carbonitrile 638.2 1 1.54 493. 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)isoquinolin-1-ol 614.2 1 1.57 494. 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1-(2-hydroxy-2- methylpropyl)-1,2-dihydroquinolin-2-one 686.3 2 1.43 495. 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)isoquinolin-1-ol 613.3 1 1.65 496. 00 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- l-(2-hydroxy-2-methylpropyl)-1,2- dihydroquinolin-2-one 685.2 1 1.75 497. 01 1-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- fluoro-1-methyl-1H-1,3-benzodiazol-2-yl}- l-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)ethan-1-ol (mixture of diastereomers) 503.3 1 1.44 498. 02 2-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-5-fluorobenzamide 608.4 1 1.33 499. 03 2-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-5-fluorobenzamide 608.4 1 1.43 500. 04 2-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- fluoro-1-methyl-1H-1,3-benzodiazol-2-yl}- l-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)butan-2-ol (mixture of diastereomers) 531.4 1 1.55 501. 05 3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-fluorophenol 587.4 1 1.64 502. 06 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2,3,4- tetrahydroisoquinolin-1-one 622.3 1 1.66 503. 07 3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-5H,6H,7H-pyrrolo[3,4- blpyridin-7-one 603.4 2 1.1 504. 08 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1H,2H,3H-pyrrolo[3,2- b]pyridin-2-one 603.1 1 1.45 505. 09 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-7-fluoro-2,3-dihydro-1H- isoindol-1-one 620.2 1 1.57 506. 0 3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 5H,6H,7H-pyrrolo[3,4-b]pyridin-7-one 602.2 1 1.41 507. 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 7-fluoro-2,3-dihydro-1H-isoindol-1-one 619.4 2 1.28 508. l-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- fluoro-1-methyl-1H-1,3-benzodiazol-2-yl}- l-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1-cyclopropylethan-1-ol (mixture of diastereomers) 543.4 2 1.55 509. 1-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- fluoro-1-methyl-1H-1,3-benzodiazol-2-yl}- l-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1-phenylethan-1-ol (mixture of diastereomers) 579.4 2 1.62 510. 7-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2,3,4- tetrahydroisoquinolin-3-one 616.2 1 1.56 511. 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2,3,4- tetrahydroquinazolin-2-one 616.9 1 1.5 512. 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-7-fluoro-1,2,3,4- tetrahydroquinolin-2-one 634.2 2 1.47 513. 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 1,2,3,4-tetrahydroquinazolin-2-one 616.2 1 1.67 514. 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 7-fluoro-1,2,3,4-tetrahydroquinolin-2-one 633.2 2 1.44 515. methyl 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-fluorobenzoate 623.4 2 1.78 516. 0 methyl 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,6-difluorobenzoate 640.9 1 2.12 517. 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 7-methoxy-1,2,3,4-tetrahydroquinolin-2- one 645 2 1.42 518. 2-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 6-fluorobenzamide 607.3 1 1.41 519. 2-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 5-fluorobenzamide 607 1 1.61 520. methyl 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 2-fluorobenzoate 622.2 2 1.79 521. methyl 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 2,6-difluorobenzoate 640.4 2 1.75 522. 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-6-fluoro-2,3-dihydro-1H- indol-2-one 620.1 1 1.74 523. 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,4-dihydro-1H-3,1- benzoxazin-2-one 618.4 2 1.31 524. 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,4-difluorobenzene-1- sulfonamide 662.2 1 1.68 525. 3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,6-difluorophenol 599.2 2 1.54 526. 0 2′-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1′-(cyclopropylmethyl)-6-fluoro-2,3- dihydro-1H,1′H-[5,6′-biindole]-2-one 619.2 2 1.38 527. 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 2,4-dihydro-1H-3,1-benzoxazin-2-one 617.3 1 1.75 528. 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 2,4-difluorobenzene-1-sulfonamide 661.1 1 1.79 529. 3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 2,6-difluorophenol 598.2 1 1.82 530. 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-5-fluoro-2-methoxyphenol 611.2 2 1.45 531. 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 5-fluoro-2-methoxyphenol 610.2 2 1.42 532. l-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-[(l-methyl-1H-pyrazol-4- yl)methyl]-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)ethan- 1-ol (mixture of diastereomers) 594.2 1 1.38 533. (7R)-2-{2-[1-(cyclopropylmethyl)-6-ethyl- 1H-indol-2-yl]-7-methoxy-1-[(1-methyl- 1H-pyrazol-4-yl)methyl]-1H-1,3- benodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 578.1 2 1.63 534. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-N-(2- hydroxyethyl)benzamide 640.4 2 1.25 535. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)benzamide 596.4 1 1.58 536. 0 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-N-methylbenzene-1- sulfonamide 646.4 2 1.48 537. 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4-methyl-1,2- dihydroquinolin-2-one 634.4 2 1.37 538. 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,3-dihydro-2-benzofuran- 1-one 609.3 1 1.83 539. 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4-fluoro-2,3-dihydro-1H- indol-2-one 620.1 1 1.61 540. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4-fluoro-2,3-dihydro-1H- indol-2-one 626.4 2 1.39 541. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-6-fluoro-2,3-dihydro-1H- indol-2-one 626.4 2 1.39 542. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1H,2H,3H-pyrrolo[2,3- b]pyridin-2-one 609.4 2 1.29 543. 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,4-dihydro-1H-3,1- benzoxazin-2-one 624.4 1 1.66 544. 3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-5H,6H,7H-pyrrolo[3,4- b]pyridin-5-one 609.4 1 1.45 545. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,4-difluorobenzene-1- sulfonamide 668.2 1 1.75 546. 0 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-7-hydroxy-1,2,3,4- tetrahydroquinolin-2-one 638.5 2 1.4 547. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,5-difluorophenol 605.3 1 1.88 548. (7R)-2-{2-[1-(cyclopropylmethyl)-6-(1- methoxyethyl)-1H-indol-2-yl]-7-methoxy- 1-[(1-methyl-1H-pyrazol-4-yl)methyl]-1H- 1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine (mixture of diastereomers) 608.4 2 1.4 549. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-hydroxybenzamide 612.2 1 1.67 550. 7-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)quinolin-4-ol 620 2 1.18 551. 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2-dihydroquinazolin-2- one 621.4 2 1.4 552. 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,8-naphthyridin-2-ol 621.2 2 1.22 553. 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)quinolin-2-ol 620.1 1 1.65 554. 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)quinoline-2,4-diol 636.4 1 1.45 555. 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-methylquinolin-4-ol 634.2 1 1.55 556. 0 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)isoquinolin-1-ol 620.3 1 1.62 557. methyl 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-hydroxybenzoate 627 1 2.17 558. methyl 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-hydroxybenzoate 621.2 1 2.19 559. 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-methylquinolin-4-ol 628.2 1 1.53 560. 5-(2-{5-[(3S,4R)-3-amino-4- hydroxypiperidine-1-carbonyl]-7-methoxy- 1-methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3-dihydro-1H-indol-2- one 606.2 2 1.35 561. 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)quinolin-1-ium-1-olate 620.4 1 1.39 562. 7-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)isoquinolin-2-ium-2-olate 620.1 1 1.57 563. 7-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)quinazolin-4-ol 621.2 2 1.22 564. 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)quinoxalin-2-ol 621.4 2 1.26 565. 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2-dihydroisoquinolin-1- one 620.2 2 1.47 566. 0 methyl 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-5-methyl-1H-pyrazole-3- carboxylate 609.1 2 1.14 567. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-fluorobenzamide 614.4 1 1.44 568. methyl 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-fluorobenzoate 629.1 2 1.83 569. ethyl 2-[4-(2-(5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenoxy]acetate 655.2 2 1.68 570. 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1H,2H,3H-imidazo[4,5- b]pyridin-2-one 610.3 1 1.21 571. 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-8-fluoro-1,2- dihydroquinolin-2-one 638.1 1 1.58 572. 7-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2,3,4- tetrahydroquinazoline-2,4-dione 637.1 1 1.49 573. 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-7-methoxy-l,2,3,4- tetrahydroquinolin-2-one 652.2 1 1.54 574. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-methoxybenzamide 626.5 1 1.37 575. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2,3,4- tetrahydroisoquinolin-1-one 622.2 1 1.56 576. 0 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-7-fluoro-2,3-dihydro-1H- indol-2-one 626.4 2 1.38 577. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2,3,4- tetrahydroquinazoline-2,4-dione 637.5 1 1.29 578. methyl 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-5-tnethyl-1H-pyrazole-3- carboxylate 615.1 2 1.3 579. methyl 2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridine-6-carboxylate 535.4 2 1.4 580. 3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)cyclobutan-1-ol (mixture of diastereomers) 547.4 2 1.2 581. (3R,5R)-1-(2-[6-(azetidin-3-yl)-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl}-5- fluoropiperidin-3-amine 532.5 1 1.02 582. (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6- {2H,3H,4H-pyrido[3,2-b][1,4]oxazin-7- yl}-1H-pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3-benzodiazole-5- carbonyl}-5-fluoropiperidin-3-amine 611.4 1 1.5 583. (7R)-2-{2-[1-(cyclopropylmethyl)-6- {2H,3H,4H-pyrido[3,2-b][1,4]oxazin-7- yl}-1H-pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3-benzodiazole-5- carbonyl}-2-azabicyclo[2.2.1]heptan-7- amine 605.5 1 1.52 584. 5-(2-(5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyrimidine-2-carbonitrile 580.4 2 1.56 585. N-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-methylpyridin-4-amine 583.4 1 1.21 586. 0 6-[(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)amino]-2,3-dihydro-1H- isoindol-1-one 623.4 1 1.35 587. 6-amino-2-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3-dihydro-1H-isoindol-1- one 623.5 1 1.5 588. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-tnethoxyphenol 599.3 1 1.65 589. 7-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4-fluoro-2,3-dihydro-1H- indol-2-one 620.4 2 1.62 590. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-6-(trifluoromethyl)-2,3- dihydro-1H-1,3-benzodiazol-2-one 677.1 1 2.03 591. 8-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-6-fluoro-3-methyl-1,2- dihydroquinoxalin-2-one 653.2 1 1.87 592. l-[4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-fluorophenoxy]-2- methylpropan-2-ol 653.5 2 1.61 593. 2-{5-[(3R,5R)-3-amino-5-fluoropiperidine- l-carbonyl]-7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-N-(4-carbamoyl-3- fluorophenyl)-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridine-6-carboxamide 657.4 1 1.52 594. 2-{5-[(3R,5R)-3-amino-5-fluoropiperidine- 1-carbonyl]-7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1-(cyclopropylmethyl)- N-(2,6-dioxopiperidin-3-yl)-1H- pyrrolo[2,3-b]pyridine-6-carboxamide 631.4 1 1.27 595. (7R)-2-{2-[1-(cyclopropylmethyl)-6-{4- [(pyridin-4-yl)methoxy]phenyl}-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 2-azabicyclo[2.2.1]heptan-7-amine 654.4 1 1.94 596. 00 2-[4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenoxy]ethan-1-ol 607.5 1 1.64 597. 01 N-[2-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]methanesulfonamide 640 1 1.91 598. 02 2-[4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenoxy]ethan-1-ol 613.4 2 1.47 599. 03 N-[2-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]formamide 596.2 2 1.62 600. 04 2-{5-[(3R,5R)-3-amino-5-fluoropiperidine- 1-carbonyl]-7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1-(cyclopropylmethyl)- N-(4-sulfamoylphenyl)-1H-pyrrolo[2,3- b]pyridine-6-carboxamide 675 1 1.57 601. 05 2-{5-[(3R,5R)-3-amino-5-fluoropiperidine- l-carbonyl]-7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1-(cyclopropylmethyl)- N-(4-hydroxy-3-methoxyphenyl)-1H- pyrrolo[2,3-b]pyridine-6-carboxamide 642.5 1 1.52 602. 06 2-{5-[(3R,5R)-3-amino-5-fluoropiperidine- 1-carbonyl]-7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1-(cyclopropylmethyl)- N-[3-(hydroxymethyl)pyridin-4-yl]-1H- pyrrolo[2,3-b]pyridine-6-carboxamide 627.4 1 1.46 603. 07 2-{5-[(3R,5R)-3-amino-5-fluoropiperidine- l-carbonyl]-7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1-(cyclopropylmethyl)- N-(3-sulfamoylphenyl)-1H-pyrrolo[2,3- b]pyridine-6-carboxamide 675.2 1 1.5 604. 08 2-{5-[(3R,5R)-3-amino-5-fluoropiperidine- 1-carbonyl]-7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1-(cyclopropylmethyl)- N-(2-methylpyridin-4-yl)-1H-pyrrolo[2,3- b]pyridine-6-carboxamide 611.4 1 1.58 605. 09 7-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-6-fluoro-2,3-dihydro-1H- indol-2-one 620.5 1 1.83 606. 0 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-fluorobenzene-1- sulfonamide 644.4 1 1.58 607. 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-fluorobenzene-1- sulfonamide 644.4 2 1.41 608. 7-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-6-fluoro-2,3-dihydro-1H- indol-2-one 626.2 2 1.57 609. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-fluorobenzene-1- sulfonamide 650.4 1 1.56 610. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-fluorobenzene-1- sulfonamide 650.4 2 1.41 611. 2-{5-[(3R,5R)-3-amino-5-fluoropiperidine- 1-carbonyl]-7-methoxy-1-methyl-1H-1,3- benzodiazol-2-yl}-1-(cyclopropylmethyl)- N-[3-(hydroxymethyl)pyridin-4-yl]-1H- pyrrolo[2,3-b]pyridine-6-carboxamide 627.2 2 0.98 612. 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-(1,2-oxazol-5-yl)phenol 630.4 1 1.43 613. 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-5-methylpyridin-3-ol 578.1 1 1.57 614. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-(1,2-oxazol-5-yl)phenol 636.2 1 1.44 615. 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-5-methylpyridin-3-ol 584 2 1.19 616. 0 3-[2-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)ethyl]-1,3-oxazolidin-2-one 590 2 1.26 617. (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6- [(oxan-2-yl)methyl]-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl}-5- fluoropiperidin-3-amine 575.02 2 618. (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6-[2- (piperidin-4-yl)ethyl]-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl}-5- fluoropiperidin-3-amine 588.5 1 1.34 619. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)cyclohexan-1-ol (mixture of diastereomers) 575.46 1 620. 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-8-fluoro-1,2,3,4- tetrahydroquinolin-2-one 640.2 1 1.77 621. 2-[4-(2-(5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenoxy]acetamide 626.2 1 1.53 622. methyl 2-[4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-5-fluoro-2- methoxyphenoxy]acetate 689.2 1 1.97 623. 2-[6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridin-3-yl]acetamide 611.3 1 1.37 624. 2-[4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-fluorophenyl]-2- hydroxyacetamide (mixture of diastereomers) 644.2 2 1.12 625. 2-[4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-fluorophenyl]acetamide 628.2 2 1.37 626. 0 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,5-difluorobenzamide 632.1 1 1.7 627. 2-[6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridin-3-yl]acetamide 605.2 1 1.38 628. 2-[4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-fluorophenyl]-2- hydroxyacetamide (mixture of diastereomers) 638.3 2 1.1 629. 2-[4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-fluorophenyl]acetamide 622.2 1 1.6 630. 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,5-difluorobenzamide 626.4 2 1.3 631. 7-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2,3,4- tetrahydroisoquinolin-1-one 621.9 1 1.68 632. (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6- (3,5-dimethyl-1,2-oxazol-4-yl)-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 5-fluoropiperidin-3-amine 572.2 1 1.72 633. (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6- {4-[(5-methyl-1,3,4-oxadiazol-2- yl)methoxy]phenyl}-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl}-5- fluoropiperidin-3-amine 665.1 1 1.68 634. (7R)-2-{2-[1-(cyclopropylmethyl)-6-{4- [(5-methyl-1,3,4-oxadiazol-2- yl)methoxy]phenyl}-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 659.2 2 1.48 635. 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2,3,4-tetrahydro-1,8- naphthyridin-2-one 623.3 3 0.68 636. 0 7-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2H,3H,4H-pyrido[3,2- b][1,4]oxazin-3-one 625.2 2 1.4 637. 7-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1H,2H,3H-pyrido[2,3- b][1,4]oxazin-2-one 625.1 2 1.35 638. 7-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3,4-dihydro-2H-1,4- benzoxazin-3-one 624.2 1 1.58 639. 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3,4-dihydro-2H-1,4- benzoxazin-3-one 624.1 2 1.45 640. (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6-(6- methanesulfonylpyridin-3-yl)-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 5-fluoropiperidin-3-amine 632.2 2 1.35 641. 7-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2H,3H,4H-pyrido[3,2- b][1,4]oxazin-3-one 619.2 1 1.58 642. 7-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1H,2H,3H-pyrido[2,3- b][1,4]oxazin-2-one 619.3 1 1.37 643. 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3,4-dihydro-2H-1,4- benzoxazin-3-one 618.2 1 1.64 644. 4-[4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]azetidin-2-one 622.2 1 1.76 645. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-fluoropyridine-2- carboxamide 615.1 1 1.46 646. 0 [5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3-dihydro-1-benzofuran- 2-yl]methanol 625.2 2 1.53 647. 3-[4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]-4,5-dihydro-1,2,4- oxadiazol-5-one 637.1 2 1.59 648. 4-[4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]azetidin-2-one 616 2 1.45 649. 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-fluoropyridine-2- carboxamide 609.2 2 1.34 650. [5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3-dihydro-1-benzofuran- 2-yl]methanol 619.2 2 1.5 651. 3-[4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]-4,5-dihydro-1,2,4- oxadiazol-5-one 631.4 2 3.43 652. (7R)-2-{2-[l-(cyclopropylmethyl)-6-{4- [(1,3-oxazol-2-yl)methoxy]phenyl}-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 2-azabicyclo[2.2.1]heptan-7-amine 1287.4 1 1.93 653. methyl 2-{2-[4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenoxy]acetamido}acetate 692.2 2 1.52 654. methyl (2E)-3-[4-(2-{5-[(3R,5R)-3-amino- 5-fluoropiperidine-1-carbonyl]-7-methoxy- 1-methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]prop-2-enoate 637.2 1 2 655. (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6- {4-[(1,3-oxazol-2-yl)methoxy]phenyl}-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 5-fluoropiperidin-3-amine 650.1 1 1.9 656. 0 N-[5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridin-2-yl]acetamide 306 2 1.32 657. (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6- (2,3-dihydro-1-benzofuran-5-yl)-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 5-fluoropiperidin-3-amine 595.2 1 2.05 658. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridine-2-carboxamide 596.9 2 1.32 659. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,3-dihydro-2-benzofuran- 1-one 608.9 2 1.52 660. 2-methoxyethyl N-[5-(2-{5-[(3R,5R)-3- amino-5-fluoropiperidine-1-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridin-2-yl]carbamate 336.3 1 1.71 661. (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6- (2,3-dihydro-1-benzofuran-6-yl)-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 5-fluoropiperidin-3-amine 595.2 1 1.97 662. (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6- (2,3-dihydro-1,4-benzodioxin-6-yl)-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 5-fluoropiperidin-3-amine 611.2 2 1.68 663. 3-[3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]propanoic acid 619.2 1 1.44 664. ethyl 2-[5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridin-2-yl]acetate 640.2 2 1.42 665. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridin-3-ol 570.1 1 1.42 666. 0 [5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridin-2-yl]methanol 584.2 1 1.41 667. [4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-5-fluoro-2- methoxyphenyl]methanol 631.2 2 1.6 668. 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3-dihydro-1-benzofuran- 3-one 603.2 1 1.85 669. 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-fluoropyridin-3-ol 582.2 2 1.43 670. 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-fluoropyridin-3-ol 582.2 2 1.49 671. 1-[4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridin-2-yl]pyrrolidin-2- one 316 2 1.48 672. [4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-5-fluoro-2- methoxyphenyl]methanol 625.2 2 1.56 673. [4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3,5- difluorophenyl]methanol 613.2 1 1.6 674. [4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-fluorophenyl]methanol 595.2 2 1.52 675. [4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3,5- difluorophenyl]methanol 619.2 1 1.65 676. 0 [4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-fluorophenyl]methanol 601.2 1 1.69 677. 2-[4-(2-(5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenoxy]-N- (cyanomethyl)acetamide 665.2 2 1.51 678. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-N,N-dimethylpyridine-2- carboxamide 625.2 2 1.27 679. 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2H,3H-[1,3]oxazolo[4,5- blpyridin-2-one 611.2 1 1.43 680. [2-amino-5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridin-3-yl]methanol 599.2 1 1.24 681. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-methoxypyridin-3-ol 600.1 2 1.35 682. [4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]methanesulfonamide 646.1 2 1.42 683. (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6- {2H,3H,4H-pyrido[3,2-b][1,4]oxazin-6- yl}-1H-pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3-benzodiazole-5- carbonyl}-5-fluoropiperidin-3-amine 611.2 2 1.34 684. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-6-fluoropyridin-3-ol 588.1 1 1.6 685. [5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-fluoropyridin-2- yl]methanol 602.1 2 1.24 686. 0 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2H,3H-[1,3]oxazolo[4,5- b]pyridin-2-one 605.2 1 1.45 687. [2-amino-5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridin-3-yl]methanol 593.3 1 1.27 688. 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-methoxypyridin-3-ol 594.2 1 1.55 689. [4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]methanesulfonamide 640.1 2 1.26 690. 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-6-fluoropyridin-3-ol 582 1 1.51 691. [5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-fluoropyridin-2- yl]methanol 596.2 1 1.59 692. 1-[5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-6-methoxypyridin-2- yl]pyrrolidin-2-one 667.1 1 1.93 693. 1-[5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridin-2-yl]-3- hydroxypyrrolidin-2-one (mixture of diastereomers) 653.3 1 1.42 694. l-[5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-methylpyridin-2-yl]-3- hydroxypyrrolidin-2-one (mixture of diastereomers) 667.1 1 1.35 695. 1-[4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]-3- hydroxypiperidin-2-one (mixture of diastereomers) 666 2 1.51 696. 00 l-[4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]imidazolidin-2-one 637.3 2 1.36 697. 01 1-[4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]pyrrolidin-2-one 636 2 1.64 698. 02 l-[5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-6-methoxypyridin-2- yl]pyrrolidin-2-one 661.1 2 1.68 699. 03 1-[5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridin-2-yl]-3- hydroxypyrrolidin-2-one (mixture of diastereomers) 647.1 1 1.45 700. 04 l-[5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-methylpyridin-2-yl]-3- hydroxypyrrolidin-2-one (mixture of diastereomers) 661.2 2 1.2 701. 05 1-[4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]-3- hydroxypiperidin-2-one (mixture of diastereomers) 660.4 1 1.48 702. 06 l-[4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]imidazolidin-2-one 631.2 2 1.33 703. 07 1-[4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]pyrrolidin-2-one 630.2 2 1.6 704. 08 2-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-5-hydroxybenzonitrile 594.2 2 1.5 705. 09 3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4-hydroxybenzonitrile 594.3 1 1.79 706. 0 2-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-5-hydroxybenzonitrile 588.3 1 1.55 707. 3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4-hydroxybenzonitrile 588.1 2 1.7 708. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-methoxyphenol 599.3 1 1.62 709. 2-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)benzonitrile 578.1 2 1.72 710. 3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-fluorobenzonitrile 596 1 1.86 711. 3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4-fluorophenol 587.1 2 1.5 712. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-N-methylpyridine-2- carboxamide 611.1 1 1.49 713. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,4-difluorophenol 605.2 1 1.74 714. l-[4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-fluorophenyl]-3- hydroxypiperidin-2-one (mixture of diastereomers) 684.3 2 1.41 715. 4-[4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]-2,3-dihydro-1H- iniidazol-2-one 635.4 2 1.22 716. 0 3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)benzonitrile 572.2 1 2.04 717. 2-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)benzonitrile 572.4 1 1.9 718. 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-methoxyphenol 593.2 1 1.76 719. 3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-fluorobenzonitrile 590.2 1 1.9 720. 2-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-fluoropyridin-4-ol 582.1 1 1.11 721. 1-[4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-fluorophenyl]-3- hydroxypiperidin-2-one (mixture of diastereomers) 678.3 2 1.49 722. (7R)-2-{2-[6-(6-amino-5-methoxypyridin- 3-yl)-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 2-azabicyclo[2.2.1]heptan-7-amine 593.3 1 1.58 723. 4-[4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]-2,3-dihydro-1H- imidazol-2-one 629.2 2 1.21 724. 3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4-fluorophenol 293.9 2 1.53 725. ((3R,5R)-3-amino-5-fluoropiperidin-1- yl)(2-(1-(cyclopropylmethyl)-6-(4-(1,1- dioxidoisothiazolidin-2-ylphenyl)-1H- pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1- methyl-1H-benzo[d]imidazol-5- yl)methanone 672.3 1 1.56 726. 0 5-[4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]-5- methylimidazolidine-2,4-dione 665 2 1.38 727. 7-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3,4,5-tetrahydro-1H-1,4- benzodiazepine-2,5-dione 651.1 2 1.18 728. ((7R)-7-amino-2-azabicyclo[2.2.1]heptan- 2-yl)(2-(1-(cyclopropylmethyl)-6-(4-(1,1- dioxidoisothiazolidin-2-yl)phenyl)-1H- pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1- methyl-1H-benzo[d]imidazol-5- yl)methanone 666.2 1 1.67 729. 5-[4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]-5- methylimidazolidine-2,4-dione (mixture of diastereomers) 659 1 1.53 730. 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-methoxy-1,2- dihydropyridin-2-one 594.2 2 1.2 731. 7-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3,4,5-tetrahydro-1H-1,4- benzodiazepine-2,5-dione 645.2 2 1.24 732. 7-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)quinolin-2-ol 620.18 2 1.34 733. (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6-[4- (methanesulfonylmethyl)phenyl]-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 5-fluoropiperidin-3-amine 645.2 2 1.52 734. 2-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridin-4-ol 570.2 2 1.09 735. N-[5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridin-2-yl]-2,2- dimethylpropanamide 653.4 1 1.86 736. 0 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2-dihydropyridin-2-one 570.1 2 1.18 737. N-[4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6- yl)phenyl]cyclopropanesulfonamide 672.2 2 1.58 738. N-[4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]-2,2- dimethylpropanamide 646 2 1.69 739. N-[5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridin-2-yl]-2,2- dimethylpropanamide 647 1 2.02 740. 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2-dihydropyridin-2-one 564.2 1 1.21 741. N-[4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6- yl)phenyl]cyclopropanesulfonamide 666 1 1.82 742. 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)isoquinolin-3-ol 614.2 1 1.47 743. (7R)-2-{2-[1-(cyclopropylmethyl)-6-[4- (methanesulfonylmethyl)phenyl]-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 2-azabicyclo[2.2.1]heptan-7-amine 639.2 2 1.45 744. 2-(2-(5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridin-4-ol 564 1 1.27 745. 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2-dihydropyridin-2-one 564.2 1 1.44 746. 0 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)-2- fluorophenol 586.4 2 1.58 747. 3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)-2- fluorophenol 586.2 2 1.47 748. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)-2- methoxyphenol 598 1 1.65 749. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)-2,5- difluorophenol 604.2 1 1.75 750. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)-N-(2- hydroxyethyl)benzamide 639.2 1 1.45 751. N-[5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6- yl)pyridin-2-yl]acetamide 610.2 1 1.56 752. 2′-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1′- (cyclopropylmethyl)-2,3-dihydro-1H,1′H- [5,6′-biindole]-2-one 607 2 1.38 753. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 1H,2H,3H-pyrrolo[2,3-b]pyridin-2-one 608.1 1 1.53 754. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)-1- methyl-1,2-dihydropyridin-2-one 582.9 1 1.41 755. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1-methyl-1,2- dihydropyridin-2-one 584.2 2 1.31 756. 0 3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-chlorophenol 603.2 1 1.7 757. 3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-methylphenol 583 1 1.7 758. 3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-methoxyphenol 599.2 1 1.68 759. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,4-dimethyl-1,2- dihydropyridin-2-one 597.9 2 1.32 760. 3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-chlorophenol 597.4 1 1.72 761. 3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-methoxyphenol 593.2 1 1.6 762. 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,4-dimethyl-1,2- dihydropyridin-2-one 592 1 1.33 763. 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)benzene-1,3-diol 578.9 1 1.47 764. l-[6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-methylpyridin-3-yl]-3- hydroxypyrrolidin-2-one 661.3 1 1.51 765. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)benzene-1,3-diol 585.2 1 1.42 766. 0 l-[6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-methylpyridin-3-yl]-3- hydroxypyrrolidin-2-one 667.2 1 1.37 767. (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6- (2H,3H,4H-pyrido[3,2-b][1,4]oxazin-7- yl}-1H-indol-2-yl]-7-methoxy-1-methyl- 1H-1,3-benzodiazole-5-carbonyl}-5- fluoropiperidin-3-amine 610 2 1.23 768. 3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 5H,6H,7H-pyrrolo[3,4-b]pyridin-5-one 608.1 1 1.47 769. 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 1H,2H,3H-imidazo[4,5-b]pyridin-2-one 608.9 2 1.19 770. 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6- yl)quinolin-1-ium-1-olate 619.2 1 1.49 771. 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 1,2,3,4-tetrahydro-1,8-naphthyridin-2-one 622.2 2 1.35 772. 7-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6- yl)isoquinolin-2-ium-2-olate 619.2 1 1.47 773. 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6- yl)cinnolin-4-ol 620 1 1.38 774. 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)-4- hydroxyquinoline-3-carboxylic acid 663.2 2 1.41 775. 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6- yl)quinolin-2-ol 619.2 1 1.55 776. 0 7-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 2H,3H,4H-pyrido[3,2-b][1,4]oxazin-3-one 624 2 1.41 777. (3R,5R)-1-(2-[1-(cyclopropylmethyl)-6-(1- methanesulfonylpiperidin-4-yl)-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 5-fluoropiperidin-3-amine 638.2 2 1.53 778. 7-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)- 2,3,4,5-tetrahydro-1H-1,4-benzodiazepine- 2,5-dione 649.9 1 1.38 779. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)-2- hydroxybenzamide 611.2 1 1.45 780. (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6-(6- methanesulfonylpyridin-3-yl)-1H-indol-2- yl]-7-methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-5- fluoropiperidin-3-amine 631.2 1 1.6 781. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)-2,4- difluorobenzene-1-sulfonamide 667.2 1 1.66 782. 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)-8- fluoro-4-hydroxyquinoline-3-carboxylic acid 680.92 2 1.47 783. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)-1,2- dihydropyridin-2-one 569.2 2 1.2 784. N-[4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6- yl)phenyl]methanesulfonamide 645.2 1 1.65 785. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)-N,N- dimethylpyridine-2-carboxamide 624.2 2 1.3 786. 0 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)-N- methylpyridine-2-carboxamide 610.2 1 1.61 787. 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridine-3-carbonitrile 573 2 1.53 788. 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridine-2-carbonitrile 573.2 1 1.79 789. (7R)-2-{2-[1-(cyclopropylmethyl)-6-[4- (morpholine-4-sulfonyl)phenyl]-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 2-azabicyclo[2.2.1]heptan-7-amine 696.2 1 1.82 790. 3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-5- (hydroxymethyl)benzonitrile 608.2 2 1.54 791. N-[4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3- methoxyphenyl]methanesulfonamide 676.4 2 1.46 792. 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-8-fluoro-4- hydroxyquinoline-3-carboxylic acid 676.2 2 1.48 793. 3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-5- (hydroxymethyl)benzonitrile 601.9 1 1.67 794. N-[4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3- methoxyphenyl]methanesulfonamide 670.2 2 1.44 795. 2-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-6-fluoro-1,2,3,4- tetrahydroisoquinolin-1-one 640 2 1.73 796. 000 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-fluoro-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6- yl)quinazoline-2,4-diol 625.4 2 1.26 797. 001 6-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-fluoro-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)-2,3- dihydro-1H-isoindol-1-one 596.2 1 1.52 798. 002 methyl 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2- cyclopropaneamidopyridine-4-carboxylate 689.2 1 1.64 799. 003 N-[5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4-chloropyridin-2- yl]acetamide 639.1 1 1.73 800. 004 [2-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridin-4-yl]methanol 578.2 1 1.52 801. 005 [6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridin-3-yl]methanol 578 2 1.08 802. 006 (7R)-2-{2-[1-(cyclopropylmethyl)-6- {[1,2,3,4]tetrazolo[1,5-a]pyridin-6-yl}-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 2-azabicyclo[2.2.1]heptan-7-amine 589.2 1 1.54 803. 007 methyl 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2- cyclopropaneamidopyridine-4-carboxylate 695.2 1 1.71 804. 008 N-[5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4-chloropyridin-2- yl]acetamide 645.2 2 1.52 805. 009 [3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,5- difluorophenyl]methanol 619 1 1.61 806. 010 (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6- {[1,2,3,4]tetrazolo[1,5-a]pyridin-6-yl}-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 5-fluoropiperidin-3-amine 595 2 1.44 807. 011 (7R)-2-{2-[1-(cyclopropylmethyl)-6-(2- methoxy-3-methylpyridin-4-yl)-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 2-azabicyclo[2.2.1]heptan-7-amine 592.1 2 1.74 808. 012 3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,4-dimethylphenol 591.2 1 1.7 809. 013 [3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-methylphenyl]urea 619.1 2 1.38 810. 014 N-[5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-hydroxypyridin-2- yl]acetamide 621.2 1 1.58 811. 015 N-[5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-(hydroxymethyl)pyridin- 2-yl]acetamide 635.2 1 1.6 812. 016 (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6-(2- methoxy-3-methylpyridin-4-yl)-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 5-fluoropiperidin-3-amine 598.1 1 1.9 813. 017 3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,4-dimethylphenol 597.2 1 1.68 814. 018 [3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-methylphenyl]urea 625.2 1 1.43 815. 019 2-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2H-indazol-5-ol 603.2 1 1.67 816. 020 3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-5-chloro-2-methylphenol 611.2 1 1.93 817. 021 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-oxo-1,2-dihydropyridine- 3-carbonitrile 589.2 1 1.45 818. 022 (7R)-2-{2-1-(cyclopropylmethyl)-6- {[1,2,3,4]tetrazolo[1,5-a]pyridin-7-yl}-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 2-azabicyclo[2.2.1]heptan-7-amine 588.9 1 1.63 819. 023 3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-5-chloro-2-methylphenol 616.9 1 1.9 820. 024 (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6- {[1,2,3,4]tetrazolo[1,5-a]pyridin-7-yl}-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 5-fluoropiperidin-3-amine 595.2 1 1.6 821. 025 5-(2-{5-[(6S,7R)-7-amino-6-hydroxy-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3-dihydro-1H-indol-2- one 618.4 2 1.25 822. 026 3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-chloro-4-fluorophenol 615.2 1 1.64 823. 027 3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-chloro-4-fluorophenol 621.4 1 1.62 824. 028 1-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)azetidin-3-ol 542.1 1 1.34 825. 029 7-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,7-diazaspiro[3.5]nonan- 2-one 609.3 2 1 826. 030 2-[4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]ethan-1-ol 591 1 1.68 827. 031 (7R)-2-{2-[1-(cyclopropylmethyl)-6-(2,3- dimethoxypyridin-4-yl)-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 608 2 1.64 828. 032 (7R)-2-{2-[1-(cyclopropylmethyl)-6-(3- fluoro-4-methanesulfonylphenyl)-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 2-azabicyclo[2.2.1]heptan-7-amine 643.1 2 1.45 829. 033 7-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,7-diazaspiro[3.5]nonan- 1-one 609.2 1 1.12 830. 034 ((7R)-7-amino-2-azabicyclo[2.2.1]heptan- 2-yl)(2-(1-(cyclopropylmethyl)-6-(3-(1,1- dioxidothiomorpholino)azetidin-1-yl)-1H- pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1- methyl-1H-benzo[d]imidazol-5- yl)methanone 659.4 1 1.58 831. 035 (7R)-2-{2-[1-(cyclopropylmethyl)-6-(3- methoxyazetidin-1-yl)-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 556.2 2 1.37 832. 036 (7R)-2-{2-[1-(cyclopropylmethyl)-6-{2- oxa-6-azaspiro[3.3]heptan-6-yl}-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 2-azabicyclo[2.2.1]heptan-7-amine 568.1 1 1.51 833. 037 7-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-hydroxy-4H-pyrido[1,2- a]pyrimidin-4-one 630.9 1 1.3 834. 038 8-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3,4-dihydro-2H-1,4- benzoxazin-3-one 618 1 1.58 835. 039 8-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1-oxa-3,8- diazaspiro[4.5]decan-2-one 625.3 1 1.13 836. 040 1-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-N-(2- hydroxyethyl)piperidine-4-carboxamide 641 1 1.28 837. 041 (7R)-2-{2-[1-(cyclopropylmethyl)-6-(4- methanesulfonylpiperidin-1-yl)-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 2-azabicyclo[2.2.1]heptan-7-amine 632.2 2 1.32 838. 042 (7R)-2-{2-[l-(cyclopropylmethyl)-6- {[1,2,4]triazolo[1,5-a]pyridin-6-yl}-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 2-azabicyclo[2.2.1]heptan-7-amine 588 2 1.4 839. 043 1-[1-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)piperidin-4-yl]pyrrolidin-2- one 319.1 2 1.4 840. 044 N-[4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]-2- methoxyacetamide 640 1 1.71 841. 045 N-[4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]-2- methoxyacetamide 634.3 1 1.64 842. 046 1-[5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2,3,4-tetrahydroquinolin- 1-yl]ethan-1-one 644.1 2 1.62 843. 047 (3R,5R)-1-{2-[6-(1,2,4-benzotriazin-6-yl)- 1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl}-5- fluoropiperidin-3-amine 606.3 1 1.66 844. 048 (3R,5R)-1-{2-[6-(1,3-benzoxazol-4-yl)-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl}-5- fluoropiperidin-3-amine 594.1 2 1.71 845. 049 (7R)-2-{2-[6-(1,2,4-benzotriazin-6-yl)-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 600.1 1 1.69 846. 050 3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4-methylphenol 583.1 1 1.6 847. 051 3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4-methylphenol 577.1 1 1.83 848. 052 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-methylphenol 577 2 1.71 849. 053 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-chloro-4-fluorophenol 620.9 1 1.99 850. 054 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-chloro-4-fluorophenol 615.3 2 1.71 851. 055 [1-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyrrolidin-3-yl]methanol (mixture of diastereomers) 570.9 1 1.63 852. 056 (7R)-2-{2-[1-(cyclopropylmethyl)-6- {4H,5H,6H,7H-pyrazolo[1,5-a]pyridin-3- yl}-1H-pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3-benzodiazole-5- carbonyl}-2-azabicyclo[2.2.1]heptan-7- amine 591 2 1.39 853. 057 ethyl 2-[4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1H-pyrazol-1-yl]acetate 623.1 1 1.69 854. 058 3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4-chlorophenol 603.3 1 1.78 855. 059 3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-5-chlorophenol 603.1 2 1.65 856. 060 3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4-chlorophenol 597.4 1 1.83 857. 061 3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)-2- chloro-4-fluorophenol 620.4 1 1.77 858. 062 (7R)-2-{2-[1-(cyclopropylmethyl)-6- {[1,2,4]triazolo[4,3-a]pyridin-7-yl}-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 2-azabicyclo[2.2.1]heptan-7-amine 588.4 2 1.19 859. 063 2-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-6-hydroxybenzonitrile 594.1 1 1.56 860. 064 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-chloro-6-methylphenol 611.1 2 1.73 861. 065 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-ethylphenol 591 2 1.65 862. 066 ethyl 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,3-dimethyl-1H-pyrazole- 5-carboxylate 637.1 2 1.61 863. 067 1-[4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1H-pyrazol-1-yl]-2- methylpropan-2-ol 609.2 1 1.54 864. 068 (7R)-2-{2-[1-(cyclopropylmethyl)-6-[3- (methoxymethyl)azetidin-1-yl]-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 2azabicyclo[2.2.1]heptan-7-amine 570.1 1 1.86 865. 069 (7R)-2-{2-[1-(cyclopropylmethyl)-6-[3- (pyridin-3-yl)azetidin-1-yl]-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 2-azabicyclo[2.2.1]heptan-7-amine 603.1 2 1.15 866. 070 1-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-N,N-dimethylazetidine-3- carboxamide 597.2 1 1.59 867. 071 ((7R)-7-amino-2-azabicyclo[2.2.1]heptan- 2-yl)(2-(1-(cyclopropylmethyl)-6-(1,1- dioxido-1-thia-6-azaspiro[3.3]heptan-6-yl)- 1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy- 1-methyl-1H-benzo[d]imidazol-5- yl)methanone 616 2 1.35 868. 072 (7R)-2-{2-[1-(cyclopropylmethyl)-6-(3- methanesulfonylazetidin-1-yl)-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 2-azabicyclo[2.2.1]heptan-7-amine 604.1 1 1.51 869. 073 (7R)-2-{2-[1-(cyclopropylmethyl)-6-{6- oxa-2-azaspiro[3.4]octan-2-yl}-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 2-azabicyclo[2.2.1]heptan-7-amine 582 2 1.43 870. 074 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-chloro-5-methylphenol 617 1 1.83 871. 075 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-methylphenol 583.1 2 1.58 872. 076 3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-(trifluoromethyl)phenol 637.3 1 1.71 873. 077 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-chloro-5-methylphenol 611.3 2 1.66 874. 078 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-methylphenol 577.2 1 1.74 875. 079 3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-(trifluoromethyl)phenol 631.2 1 1.8 876. 080 3-{[4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6- yl)phenyl]formamido}propanamide 661.1 2 1.3 877. 081 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-N-[(1- carbamoylcyclopropyl)methyl]benzamide 687.2 2 1.4 878. 082 (7R)-2-{2-[1-(cyclopropylmethyl)-6-(5- methoxy-1H-pyrazol-4-yl)-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 567.3 1 1.62 879. 083 ethyl 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,5-dimethyl-1H-pyrazole- 3-carboxylate 637.4 1 1.69 880. 084 methyl 3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1-methyl-1H-indazole-6- carboxylate 659.1 1 1.97 881. 085 (7R)-2-{2-[1-(cyclopropylmethyl)-6-(1- methyl-1H-pyrazol-3-yl)-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 551 1 1.67 882. 086 (7R)-2-{2-[1-(cyclopropylmethyl)-6- {pyrazolo[1,5-a]pyridin-3-yl}-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 2-azabicyclo[2.2.1]heptan-7-amine 587.1 2 1.62 883. 087 (7R)-2-{2-[1-(cyclopropylmethyl)-6-(1H- indazol-3-yl)-1H-pyrrolo[2,3-b]pyridin-2- yl]-7-methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.l]heptan-7-amine 587.3 1 1.75 884. 088 (7R)-2-{2-[6-(3-cyclopropyl-1H-pyrazol- 4-yl)-1-(cyclopropylmethyl)-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 2-azabicyclo[2.2.1]heptan-7-amine 577 2 1.28 885. 089 methyl 2-[1-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)piperidin-4-yl]acetate 626.2 1 1.98 886. 090 (7R)-2-{2-[l-(cyclopropylmethyl)-6-[(2R)- 2-(methoxymethyl)azetidin-1-yl]-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 2-azabicyclo[2.2.1]heptan-7-amine 570.2 2 1.44 887. 091 1-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-phenylpyrrolidin-3-ol (mixture of diastereomers) 632.2 2 1.62 888. 092 (7R)-2-{2-[1-(cyclopropylmethyl)-6-[2-(1- methyl-1H-pyrazol-4-yl)pyrrolidin-1-yl]- 1H-pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy- 1-methyl-1H-1,3-benzodiazole-5- carbonyl}-2-azabicyclo[2.2.1]heptan-7- amine (mixture of diastereomers) 620.2 2 1.51 889. 093 (3S)-1-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyrrolidine-3-carbonitrile 565.1 1 1.62 890. 094 (7R)-2-{2-[1-(cyclopropylmethyl)-6-[2- (pyridin-3-yl)pyrrolidin-1-yl]-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 2-azabicyclo[2.2.1]heptan-7-amine (mixture of diastereomers) 617.2 2 1.27 891. 095 (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6- [(2R)-2-(methoxymethyl)azetidin-1-yl]- 1H-pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy- 1-methyl-1H-1,3-benzodiazole-5- carbonyl}-5-fluoropiperidin-3-amine 576.2 1 1.84 892. 096 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-methoxyphenol 599.1 1 1.63 893. 097 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-methoxy-6-methylphenol 607.3 2 1.66 894. 098 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-methoxyphenol 593 1 1.69 895. 099 (7R)-2-{2-[1-(cyclopropylmethyl)-6-[3- (pyridin-4-yl)pyrrolidin-1-yl]-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 2-azabicyclo[2.2.1]heptan-7-amine (mixture of diastereomers) 617.2 2 1.07 896. 00 3-{[4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]formamido}-2,2- dimethylpropanamide 695 1 1.49 897. 01 [4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-chloro-5- fluorophenyl]methanol 635.1 2 1.61 898. 02 3-{[4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]formamido}-2,2- dimethylpropanamide 689.2 1 1.61 899. 03 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-7aH-pyrrolo[3,2- b]pyridine-3-carboxamide 629.9 1 1.41 900. 04 1-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1-cyclopropylethan-1-ol (mixture of diastereomers) 561.2 2 1.67 901. 05 3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)-2- (trifluoromethyl)phenol 636.3 1 1.79 902. 06 3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)-2- methoxyphenol 598.1 2 1.6 903. 07 3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)-2,4- dimethylphenol 596.1 1 1.87 904. 08 3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)-2- methylphenol 582.1 2 1.59 905. 09 3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)-2- chlorophenol 602.1 2 1.65 906. 0 1-[5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2,3,4- tetrahydroisoquinolin-2-yl]ethan-1-one 650.2 1 1.76 907. 2-[4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2- hydroxyphenyl]acetamide 625.9 1 1.49 908. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1H,2H,3H-pyrrolo[2,3- b]pyridin-2-one 609.1 1 1.49 909. [4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-methoxyphenyl]methanol 613.3 2 1.43 910. 1-[6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-8-fluoro-1,2,3,4- tetrahydroisoquinolin-2-yl]ethan-1-one 662.1 2 1.52 911. 1-[5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,2,3,4- tetrahydroisoquinolin-2-yl]ethan-1-one 644 1 1.73 912. 2-[4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2- methoxyphenyl]acetamide 633.9 1 1.6 913. 2-[4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,6- difluorophenyl]acetamide 640.2 1 1.64 914. 2-[4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-fluorophenyl]acetamide 622.2 2 1.27 915. 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1H,2H,3H-pyrrolo[2,3- blpyridin-2-one 603.3 1 1.56 916. 0 [4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-methoxyphenyl]methanol 1213.3 1 1.63 917. (7R)-2-{2-[1-(cyclopropylmethyl)-6-{2- oxa-6-azaspiro[3.3]heptan-6-yl}-1H-indol- 2-yl]-7-methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 567 2 1.15 918. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-5-fluoro-2-methoxyphenol 617.2 1 1.8 919. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridine-2-carboxamide 597.2 1 1.53 920. 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3,5-dimethylphenol 591 1 1.72 921. [4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-methylphenyl]methanol 591.1 1 1.82 922. (7R)-2-{2-[1-(cyclopropylmethyl)-6-[3- (methoxymethyl)azetidin-1-yl]-1H-indol- 2-yl]-7-methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 569.2 2 1.36 923. (7R)-2-{2-[1-(cyclopropylmethyl)-6-(3- methoxyazetidin-1-yl)-1H-indol-2-yl]-7- methoxy-1-methyl-1H-1,3-benzodiazole-5- carbonyl}-2-azabicyclo[2.2.1]heptan-7- amine 555.2 2 1.22 924. (7R)-2-{2-[1-(cyclopropylmethyl)-6-[3- (pyridin-3-yl)azetidin-1-yl]-1H-indol-2- yl]-7-methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 602.2 1 1.69 925. 2-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-azaspiro[3.3]heptan-6-ol 582.1 1 1.63 926. 0 (7R)-2-{2-[1-(cyclopropylmethyl)-6-[3- (pyridin-2-yl)azetidin-1-yl]-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 2-azabicyclo[2.2.1]heptan-7-amine 603.1 2 1.2 927. (7R)-2-{2-[1-(cyclopropylmethyl)-6- {[1,2,4]triazolo[4,3-a]pyridin-3-yl}-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 2-azabicyclo[2.2.1]heptan-7-amine 588.3 1 1.49 928. (7R)-2-{2-[1-(cyclopropylmethyl)-6- {[1,2,4]triazolo[1,5-a]pyridin-2-yl}-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 2-azabicyclo[2.2.1]heptan-7-amine 587.9 2 1.41 929. ethyl 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,5-dimethyl-1H-pyrazole- 3-carboxylate 643.2 1 1.44 930. (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6- (1,3-dimethyl-1H-pyrazol-4-yl)-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 5-fluoropiperidin-3-amine 571.2 1 1.63 931. ethyl 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,3-dimethyl-1H-pyrazole- 5-carboxylate 643.2 1 1.69 932. methyl 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1-methyl-1H-pyrazole-5- carboxylate 615.4 2 1.53 933. (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6-(1- methyl-1H-pyrazol-5-yl)-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl}-5- fluoropiperidin-3-amine 557.2 1 1.69 934. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,5-dimethylphenol 597.2 1 1.62 935. 2-[3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]acetamide 610.4 2 1.41 936. 0 (2E)-3-[4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]prop-2-enamide 622.1 1 1.57 937. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-6-methylpyridine-2- carboxamide 611.2 1 1.55 938. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-methoxypyridine-2- carboxamide 626.9 1 1.48 939. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4-methylpyridine-2- carboxamide 611.3 1 1.4 940. 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,5-dimethylphenol 591.3 1 1.75 941. 2-[3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]acetamide 604.2 1 1.41 942. (2E)-3-[4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]prop-2-enamide 616.1 1 1.6 943. 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-6-methylpyridine-2- carboxamide 605.3 1 1.58 944. 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-methoxypyridine-2- carboxamide 621.2 1 1.51 945. 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4-methylpyridine-2- carboxamide 605.2 1 1.43 946. 0 (2E)-3-[4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-fluorophenyl]prop-2- enamide 634 1 1.69 947. 2-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)butan-2-ol (mixture of diastereomers) 549 2 1.55 948. ((7R)-7-amino-2-azabicyclo[2.2.1]heptan- 2-yl)(2-(1-(cyclopropylmethyl)-6-(3-(1,1- dioxidothiomorpholino)azetidin-1-yl)-1H- indol-2-yl)-7-methoxy-1-methyl-1H- benzo[d]imidazol-5-yl)methanone 658.1 1 1.44 949. 2-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 2-azaspiro[3.3]heptan-6-ol 581.2 2 1.15 950. 1-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1-cyclopentylethan-1-ol (mixture of diastereomers) 589.4 3 0.78 951. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)-2,3- dihydro-1H-isoindol-1-one 607.1 1 1.38 952. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3-dihydro-1H-isoindol-1- one 608.1 1 1.56 953. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3-dihydro-1H-inden-2-ol (mixture of diastereomers) 609.1 1 1.64 954. 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3-dihydro-1H-inden-2-ol (mixture of diastereomers) 603.2 2 1.59 955. (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6-(1- methyl-1H-1,2,3-triazol-4-yl)-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 5-fluoropiperidin-3-amine 558.3 1 1.45 956. 0 (3R,5R)-1-{2-[1-(cycloproplmethyl)-6-[1- methyl-3-(trifluoromethyl)-1H-pyrazol-4- yl]-1H-pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3-benzodiazole-5- carbonyl}-5-fluoropiperidin-3-amine 625.3 2 1.55 957. 3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,4-difluorophenol 604.9 1 1.57 958. 3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,4-difluorophenol 599.5 1 1.54 959. 2-[4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-chlorophenyl]propan-1- ol (mixture of diastereomers) 645.5 1 1.88 960. l-[4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]ethan-1-ol (mixture of diastereomers) 597.5 2 1.46 961. (7R)-2-{2-[1-(cyclopropylmethyl)-6-[1- methyl-3-(trifluoromethyl)-1H-pyrazol-4- yl]-1H-pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3-benzodiazole-5- carbonyl}-2-azabicyclo[2.2.1]heptan-7- amine 618.9 2 1.67 962. (7R)-2-{2-[l-(cyclopropylmethyl)-6-[5-(4- fluorophenyl)-1-methyl-1H-pyrazol-4-yl]- 1H-pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy- 1-methyl-1H-1,3-benzodiazole-5- carbonyl}-2-azabicyclo[2.2.1]heptan-7- amine 645.3 2 1.68 963. (7R)-2-{2-[1-(cyclopropylmethyl)-6-[3-(4- fluorophenyl)-1-methyl-1H-pyrazol-4-yl]- 1H-pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy- 1-methyl-1H-1,3-benzodiazole-5- carbonyl}-2-azabicyclo[2.2.1]heptan-7- amine 645 1 1.8 964. (7R)-2-{2-1-(cyclopropylmethyl)-6- {[1,2,4]triazolo[1,5-a]pyrimidin-2-yl}-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 2-azabicyclo[2.2.1]heptan-7-amine 589.1 2 1.32 965. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-fluoro-5- methylbenzamide 628.1 2 1.33 966. 0 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-5-fluoro-2- methoxybenzamide 644 1 1.52 967. 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-fluoro-5- methylbenzamide 622.1 2 1.31 968. 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-5-fluoro-2- methoxybenzamide 638.2 2 1.36 969. (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6- {[1,2,4]triazolo[1,5-a]pyrimidin-2-yl}-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 5-fluoropiperidin-3-amine 595.5 1 1.26 970. (7R)-2-{2-[1-(cyclopropylmethyl)-6-(1- methyl-1H-1,2,3,4-tetrazol-5-yl)-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 2-azabicyclo[2.2.1]heptan-7-amine 553.3 1 1.44 971. 2-[1-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)azetidin-3-yl]propan-2-ol 584.2 1 1.75 972. 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4-methylpyridine-2- carbonitrile 587.1 1 1.89 973. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyrimidine-2-carboxamide 598.1 2 1.09 974. 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyrimidine-2-carboxamide 592.2 1 1.22 975. [5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyrimidin-2-yl]methanol 579.1 1 1.26 976. 0 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-fluoro-6-methoxyphenol 611 2 1.42 977. 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-methylpyridine-2- carbonitrile 587.2 1 1.65 978. 2-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 1,1,1-trifluoropropan-2-ol (first isomer off preparative HPLC) 582.1 1 1.84 979. 2-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 1,1,1-trifluoropropan-2-ol (second isomer off preparative HPLC) 582.3 2 1.5 980. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3-dimethylphenol 597.2 1 1.9 981. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3-difluorophenol 604.9 2 1.51 982. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,6-dichloro-3- methylphenol 651.1 1 1.89 983. 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3-dimethylphenol 591.1 2 1.58 984. 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3-difluorophenol 599.3 2 1.48 985. 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,6-dichloro-3- methylphenol 645.3 1 2.07 986. 0 3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-6-hydroxy-2- methylbenzoic acid 621 1 1.29 987. 2-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 1,3-difluoropropan-2-ol 564.4 1 1.68 988. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-(hydroxymethyl)phenol 598.9 1 1.36 989. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-chlorobenzamide 630.3 1 1.31 990. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-fluoro-3- methylbenzamide 628 1 1.32 991. 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-(hydroxymethyl)phenol 593.1 2 1.36 992. 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-chlorobenzamide 624.4 1 1.29 993. 4-(2-{5-[(7R(-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]-pyridin-6-yl)-2-fluoro-3- methylbenzamide 622.2 2 1.48 994. 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3-dihydro-1H-inden-1-ol (mixture of diastereomers) 603.2 1 1.69 995. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-chloro-5- fluorobenzamide 648.1 1 1.7 996. 00 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-chloro-5- fluorobenzamide 642.2 1 1.74 997. 01 (3R,5R)-1-(2-[1-(cyclopropylmethyl)-6-[4- (methanesulfonylmethyl)phenyl]-1H-indol- 2-yl]-7-methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-5- fluoropiperidin-3-amine 644 1 1.65 998. 02 2-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)-1,1,1- trifluoropropan-2-ol (mixture of diastereomers) 588 2 1.51 999. 03 2-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1-fluoropropan-2-ol (mixture of diastereomers) 553.4 1 1.56 1000. 04 2-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)-1,1,1- trifluoropropan-2-ol (first isomer off preparative HPLC) 588.2 1 1.71 1001. 05 2-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)-1,1,1- trifluoropropan-2-ol (second isomer off preparative HPLC) 588.3 2 1.51 1002. 06 2-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,1-difluoropropan-2-ol (mixture of diastereomers) 571.3 1 1.63 1003. 07 N-[4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]acetamide 610.2 2 1.53 1004. 08 N-[4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-methylphenyl]acetamide 624.4 2 1.48 1005. 09 N-[4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-ethylphenyl]acetamide 638.2 1 1.74 1006. 0 (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6-[2- fluoro-4-(methanesulfonylmethyl)phenyl]- 1H-pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy- 1-methyl-1H-1,3-benzodiazole-5- carbonyl}-5-fluoropiperidin-3-amine 663.2 1 1.66 1007. (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6-[4- (methanesulfonylmethyl)-2-methylphenyl]- 1H-pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy- 1-methyl-1H-1,3-benzodiazole-5- carbonyl}-5-fluoropiperidin-3-amine 659.1 1 1.73 1008. (3R,5R)-1-(2-{6-[2-chloro-4- (methanesulfonylmethyl)phenyl]-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-2-yl}-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl)-5- fluoropiperidin-3-amine 679.1 2 1.55 1009. N-[5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3-dihydro-1H-inden-2- yl]acetamide (mixture of diastereomers) 650.1 2 1.5 1010. 3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-6-hydroxy-2- methylbenzamide 626.2 1 1.37 1011. N-[4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-methylphenyl]acetamide 618.2 2 1.46 1012. N-[4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-ethylphenyl]acetamide 632.2 1 1.75 1013. (7R)-2-{2-[1-(cyclopropylmethyl)-6-[2- fluoro-4-(methanesulfonylmethyl)phenyl]- 1H-pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy- 1-methyl-1H-1,3-benzodiazole-5- carbonyl}-2-azabicyclo[2.2.1]heptan-7- amine 657.2 1 1.63 1014. (7R)-2-(2-{6-[2-chloro-4- (methanesulfonylmethyl)phenyl]-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-2-yl}-7-methoxy-1-methyl-1H- 1,3-benzodiazole-5-carbonyl)-2- azabicyclo[2.2.1]heptan-7-amine 673.1 1 1.65 1015. (7R)-2-{2-[1-(cyclopropylmethyl)-6-[4- (methanesulfonylmethyl)-2-methylphenyl]- 1H-pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy- 1-methyl-1H-1,3-benzodiazole-5- carbonyl}-2-azabicyclo[2.2.1]heptan-7- amine 653.5 3 0.74 1016. 0 N-[5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,3-dihydro-1H-inden-2- yl]acetamide (mixture of diastereomers) 644 2 1.49 1017. 3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-6-hydroxy-2- methylbenzamide 620 1 1.37 1018. 2-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1-methoxypropan-2-ol (mixture of diastereomers) 565 2 1.39 1019. 3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4-fluorobenzamide 614.4 1 1.5 1020. N-[5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4-methylpyridin-2- yl]acetamide 625.2 2 1.3 1021. (2E)-N-[4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-methylphenyl]-3- ethoxyprop-2-enamide 672 1 1.87 1022. 3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-fluorobenzamide 608.4 1 1.4 1023. N-[5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4-methylpyridin-2- yl]acetamide 618.9 2 1.37 1024. 1-[4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]ethane-1,2-diol (mixture of diastereomers) 607 1 1.49 1025. 2-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,1,1-trifluoropropan-2-ol (first isomer off preparative HPLC) 589.2 1 1.82 1026. 0 2-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,1,1-trifluoropropan-2-ol (second isomer off preparative HPLC) 589.3 1 1.82 1027. 3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)thietan-3-ol 565.3 1 1.65 1028. 3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-methylbenzamide 604.2 1 1.5 1029. (7R)-2-{2-[1-(cyclopropylmethyl)-6-[3- fluoro-4-(methanesulfonylmethyl)phenyl]- 1H-pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy- 1-methyl-1H-1,3-benzodiazole-5- carbonyl}-2-azabicyclo[2.2.1]heptan-7- amine 656.9 1 1.7 1030. 8-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 1-oxa-3,8-diazaspiro[4.5]decan-2-one 624.2 1 1.23 1031. 8-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)-1-oxa- 3,8-diazaspiro[4.5]decan-2-one 630 1 1.28 1032. 8-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1-oxa-3,8- diazaspiro[4.5]decan-2-one 631.2 2 1.06 1033. 7-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 2,7-diazaspiro[3.5]nonan-1-one 608 1 1.28 1034. 7-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)-2,7- diazaspiro[3.5]nonan-1-one 614.2 1 1.24 1035. 7-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2,7-diazaspiro[3.5]nonan- 1-one 615 1 1.25 1036. 0 3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4-methylbenzamide 306 2 1.34 1037. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-ethylbenzamide 624.2 1 1.55 1038. 3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4-methylbenzamide 604.2 1 1.34 1039. 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-ethylbenzamide 618.1 2 1.42 1040. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-chlorobenzamide 630.2 1 1.47 1041. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3- (trifluoromethyl)benzamide 664.4 1 1.66 1042. (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6- [2,5-difluoro-4- (methanesulfonylmethyl)phenyl]-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 5-fluoropiperidin-3-amine 681.1 1 1.79 1043. methyl N-[3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-methylphenyl]carbamate 640.3 2 1.77 1044. methyl N-[3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2- methoxyphenyl]carbamate 656.1 1 1.86 1045. 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2- (trifluoromethyl)benzamide 657.9 1 1.64 1046. 0 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3- (trifluoromethyl)benzamide 658.4 1 1.61 1047. 3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-methylbenzoic acid 605.1 1 1.32 1048. (7R)-2-{2-[1-(cyclopropylmethyl)-6-[2,5- difluoro-4- (methanesulfonylmethyl)phenyl]-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 2-azabicyclo[2.2.1]heptan-7-amine 675.3 2 1.53 1049. (7R)-2-{2-[1-(cyclopropylmethyl)-6-[4- (methanesulfonylmethyl)-3-methylphenyl]- 1H-pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy- l-methyl-1H-1,3-benzodiazole-5- carbonyl}-2-azabicyclo[2.2.1]heptan-7- amine 653.1 1 1.72 1050. methyl N-[3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-methylphenyl]carbamate 634.2 1 1.78 1051. methyl N-[3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2- methoxyphenyl]carbamate 650.4 2 1.65 1052. 2-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,1-difluoropropan-2-ol (first isomer off preparartive HPLC) 571.5 3 0.75 1053. 2-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1,1-difluoropropan-2-ol (second isomer off preparative HPLC) 571.5 3 0.76 1054. 2-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-6-fluorobenzoic acid 615.1 2 1.57 1055. (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6-(5- methanesulfonylpyridin-2-yl)-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 5-fluoropiperidin-3-amine 632.3 2 1.55 1056. 0 (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6- {3-methyl-[1,2,4]triazolo[4,3-a]pyridin-7- yl}-1H-pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3-benzodiazole-5- carbonyl}-5-fluoropiperidin-3-amine 608.4 1 1.42 1057. 2-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-6-fluorobenzoic acid 609.4 1 1.27 1058. (7R)-2-{2-[1-(cyclopropylmethyl)-6-{3- methyl-[1,2,4]triazolo[4,3-a]pyridin-7-yl}- 1H-pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy- 1-methyl-1H-1,3-benzodiazole-5- carbonyl}-2-azabicyclo[2.2.1]heptan-7- amine 602.4 1 1.45 1059. 8-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 3-methyl-1-oxa-3,8-diazaspiro[4.5]decan- 2-one 638.2 1 1.59 1060. 8-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-methyl-1-oxa-3,8- diazaspiro[4.5]decan-2-one 639.2 2 1.38 1061. 8-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)-3- methyl-1-oxa-3,8-diazaspiro[4.5]decan-2- one 644.1 1 1.56 1062. 2-1-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)azetidin-3-yl]propan-2-ol 583.2 1 1.7 1063. 8-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 2,8-diazaspiro[4.5]decan-1-one 622.1 1 1.29 1064. (7R)-2-{2-[1-(cyclopropylmethyl)-6-(4- methanesulfonylpiperidin-1-yl)-1H-indol- 2-yl]-7-methoxy-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 631.1 1 1.52 1065. 1-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)piperidine-4-carbonitrile 578.2 1 1.73 1066. 0 2-[1-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6- yl)piperidin-4-yl]propan-2-ol 611.2 2 1.18 1067. (7R)-2-{2-[1-(cyclopropylmethyl)-6-(4- methoxypiperidin-1-yl)-1H-indol-2-yl]-7- methoxy-1-methyl-1H-1,3-benzodiazole-5- carbonyl]-2-azabicyclo[2.2.1]heptan-7- amine 583.2 1 1.8 1068. 8-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)- 2,8-diazaspiro[4.5]decan-3-one 622.2 1 1.21 1069. ((7R)-7-amino-2-azabicyclo[2.2.1]heptan- 2-yl)(2-(1-(cyclopropylmethyl)-6-(1,1- dioxido-1-thia-6-azaspiro[3.3]heptan-6-yl)- 1H-indol-2-yl)-7-methoxy-1-methyl-1H- benzo[d]imidazol-5-yl)methanone 615.3 1 1.59 1070. N-[5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4-ethylpyridin-2- yl]acetamide 639.3 1 1.7 1071. 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-methylpyridine-2- carboxamide 611.1 1 1.53 1072. 2-[5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridin-2-yl]acetamide 611.4 1 1.16 1073. methyl N-[3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-chlorophenyl]carbamate 660.4 1 1.94 1074. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-5-fluoro-2- methylbenzamide 628.2 1 1.59 1075. N-[5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4-ethylpyridin-2- yl]acetamide 633.2 2 1.4 1076. 0 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-3-methylpyridine-2- carboxamide 605.1 1 1.56 1077. 2-[5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridin-2-yl]acetamide 605.2 1 1.42 1078. methyl N-[3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-2-chlorophenyl]carbamate 654.1 1 1.97 1079. 4-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-5-fluoro-2- methylbenzamide 622.1 1 1.56 1080. methyl 5-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1-methyl-1H-pyrazole-3- carboxylate 308.4 1 1.46 1081. 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)pyridine-3-carboxamide 591.5 1 1.08 1082. [3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]methanesulfonamide 640.5 1 1.34 1083. 6-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-4-chloropyridine-3- carboxamide 625 1 1.5 1084. methyl 5-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1-methyl-1H-pyrazole-3- carboxylate 609.6 1 1.42 1085. (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6- {3-fluoro-2-methylpyrazolo[1,5-a]pyridin- 5-yl}-1H-pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3-benzodiazole-5- carbonyl}-5-fluoropiperidin-3-amine 625.2 1 2.02 1086. 0 (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6- {2-methylpyrazolo[1,5-a]pyrimidin-5-yl}- 1H-pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy- 1-methyl-1H-1,3-benzodiazole-5- carbonyl}-5-fluoropiperidin-3-amine 608.2 1 1.85 1087. (7R)-2-(2-[1-(cyclopropylmethyl)-6-{3- fluoro-2-methylpyrazolo[1,5-a]pyridin-5- yl}-1H-pyrrolo[2,3-b]pyridin-2-yl]-7- methoxy-1-methyl-1H-1,3-benzodiazole-5- carbonyl}-2-azabicyclo[2.2.1]heptan-7- amine 619.2 1 2.06 1088. 1-[3-(2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl]-3,3-dimethylurea 633.3 1 1.49 1089. 1-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-indol-6-yl)-2,2- difluoroethan-1-ol (mixture of diastereomers) 556.3 3 0.74 1090. methyl 3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)azetidine-1-carboxylate 590.2 1 1.62 1091. 1-[3-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)azetidin-1-yl]ethan-1-one 574.2 1 1.4 1092. 2-{5-[(7R)-7-amino-2- azabicyclo[2.2.1]heptane-2-carbonyl]-7- methoxy-1-methyl-1H-1,3-benzodiazol-2- yl}-1-(cyclopropylmethyl)-N,N-dimethyl- 1H-indol-6-amine 513.3 3 0.57 1093. 4-(2-{5-[(3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl]-7-methoxy-1- methyl-1H-1,3-benzodiazol-2-yl}-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)piperidin-2-one (mixture of diastereomers) 574.3 1 1.4 1094. (7R)-2-{2-[1-(cyclopropylmethyl)-6-[3- (difluoromethyl)-2-fluorophenyl]-1H- pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1- methyl-1H-1,3-benzodiazole-5-carbonyl}- 2-azabicyclo[2.2.1]heptan-7-amine 615.2 1 2.17 1095. (7R)-2-{2-[1-(cyclopropylmethyl)-6-(1,1- difluoroethyl)-1H-pyrrolo[2,3-b]pyridin-2- yl]-7-fluoro-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-2- azabicyclo[2.2.1]heptan-7-amine 523.5 3 0.85 1096. 00 (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6- (1,1-difluoroethyl)-1H-pyrrolo[2,3- b]pyridin-2-yl]-7-fluoro-1-methyl-1H-1,3- benzodiazole-5-carbonyl}-5- fluoropiperidin-3-amine 529.5 3 0.86 1097. 01 (R)-3-(4-(2-(5-((3R,5R)-3-amino-5- fluoropiperidine-1-carbonyl)-7-methoxy-1- methyl-1H-benzo[d]imidazol-2-yl)-1- (cyclopropylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)phenyl)-5- (hydroxymethyl)oxazolidin-2-one 668.2 2 1.45

Biological Assays

(391) Compounds of the present invention were assayed as inhibitors of PAD4 using the assay protocol described below.

(392) RFMS human PAD4 Functional Assay:

(393) Compounds were solubilized in 100% DMSO to achieve a 10 mM compound concentration. Compound stock solutions were stored at RT. A series of dilutions were prepared in DMSO and mixed 8 times with 20 μL mixing volume. Final top concentration of compound in the assay is 50 μM. Final assay conditions were as follows: Reaction volume: 26 μl Assay buffer: 25 mM hepes, pH 7.5, 5 mM NaCl, 1 mM DTT, 0.2 mg/ml BSA, 0.01% CHAPS, 50 μM Calcium, and 5 μM TPEN Final concentrations: 5 nM hPAD4 enzyme, 250 μM BAEE, and 0.5% DMSO Total incubation time: 30 mins compound and enzyme preincubation at 37° C., 90 min enzyme/substrate reaction, 30 min reaction with phenyl glyoxal at 37° C. Stop solution: 40 μl 5% TCA in ACN

(394) 0.13 μL of compound solution was added to 13 μL of 10 nM PAD4 in assay buffer. After 30 min 13 μl of 500 μM of BAEE was added in 25 mM hepes, pH 7.5, 5 mM NaCl, 1 mM DTT, 0.2 mg/ml BSA, 0.01% CHAPS, 50 μM Calcium, 5 μM TPEN was added and the reaction incubated for 90 min at 37° C. The enzymatic reaction was quenched by addition of 15 μl of 6.1N TCA, 100% Final Concentration is 20%, 35 μl of 8.5 mM phenyl glyoxal (final concentration 4 mM) is then added and the reaction is incubated for 30 min at 37° C.

(395) After 30 minutes the plates are spun down to remove all precipitate. The enzyme reaction was quenched with an equal volume of methanol containing internal standard (modified citrulline). Samples were loaded onto the Rapid Fire RF300 system (Agilent) wherein they were first sipped for 1000 ms and then directly loaded to a C18 separations cartridge using a mixture of acetonitrile containing 0.01% formic acid for 3000 ms desalting. The flow rate of the mobile phase was 1.5 ml/min. Once the samples were eluted from the cartridge, a mobile phase of acetonitrile containing 0.01% formic acid was used to move the samples into the mass spectrometer for 4000 ms at a flow rate of 1.25 ml/min/Sciex API5500 triple quadrupole mass spectrometer (Applied Biosystems) equipped with ESI was used to analyze the peptidyl citrulline and internal standard ions.

(396) MRM transition of product and internal standard were monitored at m/z 424.5 to 350.4 and m/z 293 to 247 respectively. The dwell time for each transition was set at 200 ms, and the ESI voltage was used at 5500 with a source temperature of 400° C. Extracted ion peaks for each transition were integrated using the Rapid Fire Integrator software. Peak area of analyte was normalized with internal standard).

(397) For a given compound example, the Table below shows the human PAD4 (hPAD4) IC.sub.50 in the rapid-fire mass spectrum (RFMS) assay.

(398) TABLE-US-00012 TABLE 11 PAD4 Activity hPAD4 RFMS Cmpd # IC.sub.50 (μM) 1. 0.022 2. 0.198 3. 0.065 4. 0.252 5. 0.086 6. 0.090 7. 0.026 8. 0.053 9. 0.157 10. 0.089 11. 0.162 12. 0.136 13. 0.103 14. 0.123 15. 0.092 16. 0.071 17. 0.106 18. 0.097 19. 0.141 20. 0.091 21. 0.103 22. 0.159 23. 0.175 24. 0.176 25. 0.119 26. 0.161 27. 0.036 28. 0.116 29. 0.134 30. 0.113 31. 0.097 32. 0.170 33. 0.106 34. 0.035 35. 0.064 36. 0.082 37. 0.080 38. 0.101 39. 0.162 40. 0.129 41. 0.055 42. 0.160 43. 0.099 44. 0.109 45. 0.112 46. 0.051 47. 0.076 48. 0.160 49. 0.090 50. 0.163 51. 0.168 52. 0.018 53. 0.045 54. 0.065 55. 0.071 56. 0.046 57. 0.077 58. 0.077 59. 0.169 60. 0.148 61. 0.077 62. 0.199 63. 0.059 64. 0.056 65. 0.020 66. 0.020 67. 0.054 68. 0.077 69. 0.091 70. 0.032 71. 0.125 72. 0.102 73. 0.107 74. 0.051 75. 0.050 76. 0.143 77. 0.141 78. 0.125 79. 0.122 80. 0.055 81. 0.137 82. 0.091 83. 0.099 84. 0.123 85. 0.097 86. 0.178 87. 0.049 88. 0.030 89. 0.019 90. 0.128 91. 0.109 92. 0.099 93. 0.112 94. 0.075 95. 0.116 96. 0.010 97. 0.049 98. 0.035 99. 0.112 100. 0.053 101. 0.110 102. 0.120 103. 0.106 104. 0.064 105. 0.015 106. 0.055 107. 0.042 108. 0.067 109. 0.039 110. 0.034 111. 0.028 112. 0.058 113. 0.083 114. 0.030 115. 0.053 116. 0.058 117. 0.074 118. 0.041 119. 0.033 120. 0.080 121. 0.110 122. 0.077 123. 0.018 124. 0.041 125. 0.102 126. 0.148 127. 0.046 128. 0.050 129. 0.016 130. 0.035 131. 0.093 132. 0.113 133. 0.032 134. 0.143 135. 0.161 136. 0.066 137. 0.188 138. 0.073 139. 0.044 140. 0.027 141. 0.136 142. 0.044 143. 0.024 144. 0.069 145. 0.023 146. 0.148 147. 0.022 148. 0.149 149. 0.097 150. 0.028 151. 0.058 152. 0.013 153. 0.191 154. 0.069 155. 0.068 156. 0.154 157. 0.139 158. 0.143 159. 0.181 160. 0.163 161. 0.025 162. 0.056 163. 0.146 164. 0.092 165. 0.112 166. 0.060 167. 0.039 168. 0.025 169. 0.081 170. 0.155 171. 0.181 172. 0.063 173. 0.142 174. 0.148 175. 0.076 176. 0.088 177. 0.039 178. 0.094 179. 0.066 180. 0.092 181. 0.065 182. 0.060 183. 0.048 184. 0.037 185. 0.058 186. 0.083 187. 0.047 188. 0.060 189. 0.084 190. 0.017 191. 0.064 192. 0.083 193. 0.027 194. 0.032 195. 0.174 196. 0.094 197. 0.047 198. 0.039 199. 0.092 200. 0.012 201. 0.037 202. 0.053 203. 0.077 204. 0.095 205. 0.058 206. 0.015 207. 0.122 208. 0.062 209. 0.052 210. 0.032 211. 0.017 212. 0.060 213. 0.040 214. 0.036 215. 0.016 216. 0.047 217. 0.018 218. 0.113 219. 0.086 220. 0.021 221. 0.036 222. 0.022 223. 0.030 224. 0.058 225. 0.086 226. 0.060 227. 0.181 228. 0.121 229. 0.155 230. 0.026 231. 0.025 232. 0.072 233. 0.078 234. 0.146 235. 0.046 236. 0.051 237. 0.054 238. 0.058 239. 0.145 240. 0.068 241. 0.083 242. 0.026 243. 0.022 244. 0.132 245. 0.030 246. 0.050 247. 0.130 248. 0.118 249. 0.137 250. 0.030 251. 0.048 252. 0.139 253. 0.186 254. 0.116 255. 0.057 256. 0.119 257. 0.110 258. 0.125 259. 0.034 260. 0.107 261. 0.046 262. 0.070 263. 0.095 264. 0.034 265. 0.059 266. 0.165 267. 0.042 268. 0.059 269. 0.151 270. 0.151 271. 0.037 272. 0.095 273. 0.051 274. 0.070 275. 0.112 276. 0.036 277. 0.186 278. 0.032 279. 0.098 280. 0.053 281. 0.131 282. 0.156 283. 0.077 284. 0.110 285. 0.186 286. 0.161 287. 0.063 288. 0.150 289. 0.048 290. 0.028 291. 0.123 292. 0.049 293. 0.051 294. 0.166 295. 0.045 296. 0.039 297. 0.034 298. 0.085 299. 0.061 300. 0.157 301. 0.097 302. 0.095 303. 0.110 304. 0.167 305. 0.060 306. 0.033 307. 0.096 308. 0.162 309. 0.115 310. 0.099 311. 0.112 312. 0.188 313. 0.122 314. 0.107 315. 0.065 316. 0.103 317. 0.113 318. 0.107 319. 0.123 320. 0.042 321. 0.029 322. 0.188 323. 0.066 324. 0.040 325. 0.091 326. 0.042 327. 0.022 328. 0.127 329. 0.037 330. 0.039 331. 0.062 332. 0.030 333. 0.046 334. 0.057 335. 0.017 336. 0.064 337. 0.062 338. 0.038 339. 0.031 340. 0.042 341. 0.033 342. 0.035 343. 0.061 344. 0.040 345. 0.024 346. 0.087 347. 0.124 348. 0.141 349. 0.059 350. 0.092 351. 0.179 352. 0.028 353. 0.029 354. 0.192 355. 0.073 356. 0.023 357. 0.019 358. 0.019 359. 0.023 360. 0.016 361. 0.079 362. 0.052 363. 0.104 364. 0.013 365. 0.034 366. 0.027 367. 0.013 368. 0.038 369. 0.021 370. 0.146 371. 0.034 372. 0.136 373. 0.073 374. 0.062 375. 0.013 376. 0.066 377. 0.069 378. 0.059 379. 0.027 380. 0.107 381. 0.148 382. 0.176 383. 0.199 384. 0.128 385. 0.189 386. 0.052 387. 0.011 388. 0.013 389. 0.101 390. 0.024 391. 0.144 392. 0.009 393. 0.011 394. 0.052 395. 0.012 396. 0.025 397. 0.278 398. 0.236 399. 0.771 400. 0.209 401. 0.331 402. 0.638 403. 0.335 404. 0.252 405. 0.209 406. 0.222 407. 0.088 408. 0.079 409. 0.151 410. 0.161 411. 0.083 412. 0.155 413. 0.095 414. 0.122 415. 0.050 416. 0.168 417. 0.034 418. 0.165 419. 0.042 420. 0.045 421. 0.023 422. 0.105 423. 0.089 424. 0.070 425. 0.069 426. 0.051 427. 0.089 428. 0.143 429. 0.079 430. 0.090 431. 0.037 432. 0.047 433. 0.052 434. 0.043 435. 0.041 436. 0.049 437. 0.098 438. 0.153 439. 0.141 440. 0.095 441. 0.099 442. 0.086 443. 0.110 444. 0.281 445. 0.034 446. 0.039 447. 0.027 448. 0.075 449. 0.116 450. 0.021 451. 0.145 452. 0.157 453. 0.051 454. 0.102 455. 0.135 456. 0.061 457. 0.060 458. 0.113 459. 0.030 460. 0.038 461. 0.139 462. 0.031 463. 0.076 464. 0.057 465. 0.016 466. 0.028 467. 0.061 468. 0.028 469. 0.123 470. 0.012 471. 0.031 472. 0.072 473. 0.005 474. 0.023 475. 0.018 476. 0.013 477. 0.034 478. 0.022 479. 0.116 480. 0.014 481. 0.043 482. 0.020 483. 0.028 484. 0.025 485. 0.101 486. 0.031 487. 0.184 488. 0.082 489. 0.058 490. 0.038 491. 0.156 492. 0.048 493. 0.016 494. 0.050 495. 0.030 496. 0.044 497. 0.033 498. 0.046 499. 0.046 500. 0.032 501. 0.066 502. 0.058 503. 0.026 504. 0.174 505. 0.019 506. 0.032 507. 0.032 508. 0.049 509. 0.073 510. 0.044 511. 0.042 512. 0.045 513. 0.026 514. 0.041 515. 0.047 516. 0.199 517. 0.042 518. 0.115 519. 0.063 520. 0.103 521. 0.112 522. 0.029 523. 0.071 524. 0.027 525. 0.063 526. 0.047 527. 0.118 528. 0.052 529. 0.054 530. 4.075 531. 0.102 532. 0.048 533. 0.034 534. 0.194 535. 0.107 536. 0.168 537. 0.076 538. 0.191 539. 0.043 540. 0.054 541. 0.055 542. 0.049 543. 0.072 544. 0.087 545. 0.045 546. 0.064 547. 0.154 548. 0.107 549. 0.057 550. 0.052 551. 0.031 552. 0.025 553. 0.051 554 0.150 555. 0.132 556. 0.029 557. 1.270 558. 0.112 559. 0.065 560. 0.192 561. 0.097 562. 0.074 563. 0.026 564. 0.021 565. 0.049 566. 0.051 567. 0.081 568. 0.138 569. 0.157 570. 0.018 571. 0.058 572. 0.070 573. 0.074 574. 0.180 575. 0.055 576. 0.064 577. 0.024 578. 0.083 579. 0.175 580. 0.053 581. 0.167 582. 0.046 583. 0.137 584. 0.094 585. 0.061 586. 0.184 587. 0.169 588. 0.243 589. 0.181 590. 0.101 591. 0.192 592. 0.140 593. 0.113 594. 0.137 595. 0.189 596. 0.025 597. 0.175 598. 0.107 599. 0.059 600. 0.124 601. 0.172 602. 0.020 603. 0.055 604. 0.081 605. 0.018 606. 0.026 607. 0.021 608. 0.045 609. 0.054 610. 0.033 611. 0.050 612. 0.062 613. 0.028 614. 0.104 615. 0.054 616. 0.089 617. 0.132 618. 0.029 619. 0.072 620. 0.048 621. 0.105 622. 0.138 623. 0.142 624. 0.082 625. 0.059 626. 0.037 627. 0.176 628. 0.059 629. 0.075 630. 0.031 631. 0.087 632. 0.115 633. 0.073 634. 0.063 635. 0.035 636. 0.021 637. 0.162 638. 0.020 639. 0.192 640. 0.129 641. 0.022 642. 0.033 643. 0.081 644. 0.083 645. 0.063 646. 0.123 647. 0.157 648. 0.040 649. 0.075 650. 0.049 651. 0.088 652. 0.124 653. 0.162 654. 0.177 655. 0.158 656. 0.043 657. 0.132 658. 0.047 659. 0.039 660. 0.036 661. 0.195 662. 0.118 663. 0.167 664. 0.489 665. 0.151 666. 0.162 667. 0.149 668. 0.141 669. 0.165 670. 0.147 671. 0.159 672. 0.086 673. 0.039 674. 0.140 675. 0.028 676. 0.330 677. 0.108 678. 0.147 679. 0.102 680. 0.164 681. 0.075 682. 0.068 683. 0.173 684. 0.070 685. 0.132 686. 0.071 687. 0.041 688. 0.044 689. 0.044 690. 0.048 691. 0.039 692. 0.137 693. 0.027 694. 0.144 695. 0.031 696. 0.023 697. 0.153 698. 0.094 699. 0.015 700. 0.143 701. 0.025 702. 0.037 703. 0.034 704. 0.056 705. 0.129 706. 0.035 707. 0.022 708. 0.108 709. 0.154 710. 0.113 711. 0.068 712. 0.045 713. 0.147 714. 0.050 715. 0.037 716. 0.074 717. 0.041 718. 0.024 719. 0.033 720. 0.092 721. 0.035 722. 0.163 723. 0.019 724. 0.777 725. 0.070 726. 0.149 727. 0.032 728. 0.035 729. 0.126 730. 0.185 731. 0.006 732. 0.031 733. 0.294 734. 0.134 735. 0.124 736. 0.079 737. 0.108 738. 0.043 739. 0.136 740. 0.040 741. 0.056 742. 0.108 743. 0.052 744. 0.153 745. 0.019 746. 0.175 747. 0.067 748. 1.443 749. 0.076 750. 0.045 751. 0.036 752. 0.063 753. 0.026 754. 0.038 755. 0.143 756. 0.033 757. 0.043 758. 0.036 759. 0.106 760. 0.040 761. 0.096 762. 0.048 763. 0.054 764. 0.108 765. 0.173 766. 0.175 767. 0.032 768. 0.019 769. 0.036 770. 0.068 771. 0.060 772. 0.096 773. 0.051 774. 0.103 775. 0.046 776. 0.016 777. 0.071 778. 0.023 779. 0.072 780. 0.089 781. 0.083 782. 0.180 783. 0.118 784. 0.111 785. 0.088 786. 0.032 787. 0.080 788. 0.078 789. 0.148 790. 0.112 791. 0.086 792. 0.115 793. 0.037 794. 0.064 795. 0.105 796. 2.444 797. 0.114 798. 0.117 799. 0.076 800. 0.188 801. 0.083 802. 0.092 803. 0.159 804. 0.188 805. 0.452 806. 0.109 807. 0.120 808. 0.105 809. 0.050 810. 0.050 811. 0.138 812. 0.280 813. 0.101 814. 0.064 815. 0.090 816. 0.422 817. 0.081 818. 0.062 819. 0.272 820. 0.107 821. 0.753 822. 0.093 823. 0.038 824. 0.393 825. 0.060 826. 0.480 827. 0.445 828. 0.155 829. 0.164 830. 3.551 831. 0.647 832. 0.241 833. 0.184 834. 0.060 835. 0.103 836. 0.132 837. 0.685 838. 0.024 839. 0.652 840. 1.549 841. 0.943 842. 0.037 843. 0.036 844. 1.821 845. 0.054 846. 0.653 847. 0.130 848. 2.061 849. 0.564 850. 2.222 851. 0.038 852. 0.518 853. 0.009 854. 0.074 855. 0.195 856. 0.309 857. 0.096 858. 0.149 859. 0.017 860. 0.467 861. 4.562 862. 0.451 863. 3.849 864. 1.441 865. 0.564 866. 1.622 867. 1.347 868. 1.401 869. 1.032 870. 0.238 871. 0.206 872. 0.162 873. 0.262 874. 0.478 875. 0.239 876. 0.658 877. 0.564 878. 0.141 879. 0.357 880. 1.000 881. 0.539 882. 0.064 883. 0.049 884. 0.587 885. 0.110 886. 0.264 887. 0.197 888. 0.085 889. 0.130 890. 0.113 891. 0.272 892. 0.635 893. 0.258 894. 0.047 895. 0.034 896. 0.151 897. 0.317 898. 0.447 899. 0.729 900. 2.367 901. 1.208 902. 0.281 903. 0.917 904. 0.824 905. 0.659 906. 0.045 907. 0.124 908. 0.024 909. 0.244 910. 0.080 911. 0.633 912. 1.363 913. 0.256 914. 0.130 915. 0.039 916. 0.441 917. 3.020 918. 1.145 919. 0.085 920. 0.330 921. 0.086 922. 0.126 923. 0.265 924. 1.784 925. 0.677 926. 0.059 927. 0.019 928. 0.116 929. 0.036 930. 0.162 931. 0.069 932. 0.113 933. 0.043 934. 0.064 935. 0.144 936. 0.069 937. 0.046 938. 0.040 939. 0.074 940. 0.053 941. 0.035 942. 0.038 943. 0.012 944. 0.054 945. 0.054 946. 0.076 947. 0.033 948. 0.178 949. 0.443 950. 0.025 951. 0.047 952. 0.054 953. 0.242 954. 0.194 955. 0.134 956. 0.134 957. 0.201 958. 0.221 959. 0.168 960. 0.298 961. 0.040 962. 0.180 963. 0.092 964. 0.091 965. 0.084 966. 0.182 967. 0.104 968. 0.199 969. 0.130 970. 0.198 971. 0.398 972. 0.127 973. 0.184 974. 0.043 975. 0.239 976. 0.333 977. 0.106 978. 0.007 979. 0.045 980. 0.024 981. 0.063 982. 0.170 983. 0.040 984. 0.063 985. 0.133 986. 0.043 987. 0.034 988. 0.113 989. 0.044 990. 0.057 991. 0.084 992. 0.069 993. 0.147 994. 0.199 995. 0.102 996. 0.031 997. 0.132 998. 0.042 999. 0.194 1000. 0.035 1001. 0.042 1002. 0.043 1003. 0.036 1004. 0.042 1005. 0.194 1006. 0.083 1007. 0.066 1008. 0.055 1009. 0.182 1010. 0.084 1011. 0.052 1012. 0.238 1013. 0.061 1014. 0.029 1015. 0.025 1016. 0.111 1017. 0.036 1018. 0.110 1019. 0.037 1020. 0.593 1021. 0.158 1022. 0.024 1023. 0.362 1024. 1.133 1025. 0.149 1026. 0.302 1027. 0.228 1028. 0.066 1029. 0.741 1030. 0.047 1031. 0.062 1032. 0.034 1033. 0.086 1034. 0.141 1035. 0.086 1036. 0.066 1037. 0.031 1038. 0.035 1039. 0.148 1040. 0.065 1041. 0.045 1042. 0.207 1043. 0.076 1044. 0.109 1045. 0.135 1046. 0.038 1047. 0.102 1048. 0.110 1049. 0.111 1050. 0.043 1051. 0.093 1052. 0.062 1053. 0.015 1054. 0.117 1055. 0.070 1056. 0.038 1057. 0.133 1058. 0.047 1059. 0.068 1060. 0.059 1061. 0.124 1062. 0.538 1063. 0.077 1064. 0.045 1065. 0.015 1066. 0.058 1067. 0.051 1068. 0.093 1069. 0.006 1070. 0.072 1071. 0.162 1072. 0.128 1073. 0.073 1074. 0.052 1075. 0.043 1076. 0.052 1077. 0.146 1078. 0.058 1079. 0.021 1080. 0.102 1081. 0.104 1082. 0.113 1083. 0.199 1084. 0.064 1085. 0.043 1086. 0.102 1087. 0.061 1088. 0.151 1089. 0.057 1090. 0.032 1091. 0.136 1092. 0.195 1093. 0.111 1094. 0.148 1095. 0.024 1096. 0.066 1097. 0.020