Substituted pyrazolo{4,3-D}pyrimidines as kinase inhibitors

Abstract

The present invention relates to novel compounds of formula (I) ##STR00001##
that are capable of inhibiting one or more kinases, especially SYK (Spleen Tyrosine Kinase), LRRK2 (Leucine-rich repeat kinase 2) and/or MYLK (Myosin light chain kinase) or mutants thereof. The compounds find applications in the treatment of a variety of diseases. These diseases include autoimmune diseases, inflammatory diseases, bone diseases, metabolic diseases, neurological and neurodegenerative diseases, cancer, cardiovascular diseases, allergies, asthma, alzheimer's disease, parkinson's disease, skin disorders, eye diseases, infectious diseases and hormone-related diseases.

Claims

1. A compound of formula (I) ##STR00021## wherein A is NH, O, S, C═O, NR.sup.4 or CR.sup.5R.sup.6; R.sup.1 is an optionally substituted alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl group; R.sup.2 is an optionally substituted alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl group, wherein R.sup.2 is bound to the pyrimidine ring of formula (I) via a carbon-carbon bond; R.sup.3 is a hydrogen atom, F, Cl, CH.sub.3, CF.sub.3, NO.sub.2, cyclopropyl, CN, N.sub.3, OH, SH, OMe, SMe, NHMe, NMe.sub.2 or NH.sub.2 group; R.sup.4 is an alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl group; R.sup.5 is a hydrogen atom, NO.sub.2, N.sub.3, OH, SH, NH.sub.2 or an alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl group; and R.sup.6 is a hydrogen atom, NO.sub.2, N.sub.3, OH, SH, NH.sub.2 or an alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl group; or a pharmaceutically acceptable salt, ester, solvate or hydrate thereof.

2. A compound according to claim 1, wherein A is NH.

3. A compound according to claim 1, wherein R.sup.3 is a hydrogen atom.

4. A compound according to claim 1, wherein A is NH and R.sup.3 is H.

5. A compound according to claim 1, wherein R.sup.1 is an optionally substituted aryl, heteroaryl, cycloalkyl, heterocycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, aralkyl or heteroaralkyl group.

6. A compound according to claim 1, wherein R.sup.1 is an optionally substituted phenyl or naphthyl group or an optionally substituted heteroaryl group having one or two rings containing 5, 6, 7, 8, 9 or 10 ring atoms, or an optionally substituted arylheterocycloalkyl, heteroarylcycloalkyl or heteroarylheterocycloalkyl group containing two or three rings and 9 to 20 ring atoms.

7. A compound according to claim 1, wherein R.sup.1 is a group of formula X.sup.1-L.sup.1-Y.sup.1 or a group of formula X.sup.1-L.sup.1-Y.sup.1-L.sup.2-Z.sup.1 wherein X.sup.1 is an optionally substituted phenyl group or an optionally substituted heteroaryl group containing 5 or 6 ring atoms and 1, 2, 3 or 4 heteroatoms selected from O, S and N; L.sup.1 is a bond or a group of formula —CH.sub.2—, —C(═O)—, —SO—, —SO.sub.2—, —NH—C(═O)—, —C(═O)—NH—; —C(═O)—O—, —O—C(═O)—, —NH—C(═O)—O—, —O—C(═O)—NH—, —NH—SO.sub.2—NH—, —CH.sub.2—NH—CH.sub.2—, —NH—SO.sub.2—, —SO.sub.2—NH— or —NH—C(═O)—NH—; Y.sup.1 is an optionally substituted phenyl group, an optionally substituted heteroaryl group containing 5 or 6 ring atoms and 1, 2, 3 or 4 heteroatoms selected from O, S and N, an optionally substituted C.sub.3-C.sub.7 cycloalkyl group or an optionally substituted heterocycloalkyl group containing 3, 4, 5, 6 or 7 ring atoms and 1, 2, 3 or 4 heteroatoms selected from O, S and N; L.sup.2 is a bond or a group of formula —CH.sub.2—, —C(═O)—, —SO—, —SO.sub.2—, —NH—C(═O)—, —C(═O)—NH—; —C(═O)—O—, —O—C(═O)—, —O—C(═O)—NH—, —NH—SO.sub.2—NH—, —CH.sub.2—NH—CH.sub.2—, —NH—SO.sub.2—, —SO.sub.2—NH— or —NH—C(═O)—NH—; and Z.sup.1 is an optionally substituted phenyl group, an optionally substituted heteroaryl group containing 5 or 6 ring atoms and 1, 2, 3 or 4 heteroatoms selected from O, S and N, an optionally substituted C.sub.3-C.sub.7 cycloalkyl group or an optionally substituted heterocycloalkyl group containing 3, 4, 5, 6 or 7 ring atoms and 1, 2, 3 or 4 heteroatoms selected from O, S and N.

8. A compound according to claim 1, wherein R.sup.1 is selected from the group of: ##STR00022## ##STR00023## ##STR00024## ##STR00025## ##STR00026##

9. A compound according claim 1, wherein R.sup.2 is an optionally substituted aryl, heteroaryl, cycloalkyl, heterocycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, aralkyl or heteroaralkyl group.

10. A compound according to claim 1, wherein R.sup.2 is an optionally substituted phenyl or naphthyl group or an optionally substituted heteroaryl group having one or two rings containing 5, 6, 7, 8, 9 or 10 ring atoms, or an optionally substituted arylheterocycloalkyl or heteroarylheterocycloalkyl group containing two or three rings and 9 to 20 ring atoms.

11. A compound according to claim 1, wherein R.sup.2 is a group of formula X.sup.2-L.sup.3-Y.sup.2 or a group of formula X.sup.2-L.sup.3-Y.sup.2-L.sup.4-Z.sup.2 wherein X.sup.2 is an optionally substituted phenyl group or an optionally substituted heteroaryl group containing 5 or 6 ring atoms and 1, 2, 3 or 4 heteroatoms selected from O, S and N; L.sup.3 is a bond or a group of formula —CH.sub.2—, —C(═O)—, —SO—, —SO.sub.2—, —NH—C(═O)—, —C(═O)—NH—; —C(═O)—O—, —O—C(═O)—, —NH—C(═O)—O—, —O—C(═O)—NH—, —NH—SO.sub.2—NH—, —CH.sub.2—NH—CH.sub.2—, —NH—SO.sub.2—, —SO.sub.2—NH— or —NH—C(═O)—NH—; Y.sup.2 is an optionally substituted phenyl group, an optionally substituted heteroaryl group containing 5 or 6 ring atoms and 1, 2, 3 or 4 heteroatoms selected from O, S and N, an optionally substituted C.sub.3-C.sub.7 cycloalkyl group or an optionally substituted heterocycloalkyl group containing 3, 4, 5, 6 or 7 ring atoms and 1, 2, 3 or 4 heteroatoms selected from O, S and N; L.sup.4 is a bond or a group of formula —CH.sub.2—, —C(═O)—, —SO—, —SO.sub.2—, —NH—C(═O)—, —C(═O)—NH—; —C(═O)—O—, —O—C(═O)—, —NH—C(═O)—O—, —O—C(═O)—NH—, —NH—SO.sub.2—NH—, —CH.sub.2—NH—CH.sub.2—, —NH—SO.sub.2—, —SO.sub.2—NH— or —NH—C(═O)—NH—; and Z.sup.2 is an optionally substituted phenyl group, an optionally substituted heteroaryl group containing 5 or 6 ring atoms and 1, 2, 3 or 4 heteroatoms selected from O, S and N, an optionally substituted C.sub.3-C.sub.7 cycloalkyl group or an optionally substituted heterocycloalkyl group containing 3, 4, 5, 6 or 7 ring atoms and 1, 2, 3 or 4 heteroatoms selected from O, S and N.

12. A compound according to claim 1, wherein R.sup.2 is selected from the group of: ##STR00027## ##STR00028## ##STR00029##

13. A compound according to claim 1 exemplified as follows: N-(1H-indazol-5-yl)-5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1H-benzo[d][1,2,3]triazol-5-yl)-5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-phenyl-N-(4-(piperidin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N1,N1-dimethyl-N4-(5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)benzene-1,4-diamine; 3-((5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)benzamide; N-(3,4-dimethoxyphenyl)-5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-morpholinophenyl)-5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3-methoxyphenyl)-5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(2-methyl-1H-benzo[d]imidazol-5-yl)-5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 4-((5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)benzoic acid; 4-((5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)benzamide; 4-((5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)benzonitrile; N-(1H-indazol-5-yl)-5-(pyridin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1H-indazol-5-yl)-5-(6-(pyrrolidin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 2-((5-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)benzamide; N-(1H-indazol-6-yl)-5-(pyridin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N1,N1-dimethyl-N4-(5-(pyridin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)benzene-1,4-diamine; N-(3,4-dimethoxyphenyl)-5-(pyridin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-morpholinophenyl)-5-(pyridin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-(4-methylpiperazin-1-yl)phenyl)-5-(pyridin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 6-((5-(pyridin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2H-benzo[b][1,4]oxazin-3(4H)-one; 5-(3,4-dimethoxyphenyl)-N-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N1-(5-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-N4,N4-dimethylbenzene-1,4-diamine; N,5-bis(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(3,4-dimethoxyphenyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 6-((5-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2H-benzo[b][1,4]oxazin-3(4H)-one; N-(1H-indazol-6-yl)-5-(1-methylpiperidin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N1,N1-dimethyl-N4-(5-(1-methylpiperidin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)benzene-1,4-diamine; N-(4-chlorophenyl)-5-(1-methylpiperidin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1H-indazol-6-yl)-5-(6-(pyrrolidin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N1,N1-dimethyl-N4-(5-(6-(pyrrolidin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)benzene-1,4-diamine; N-(3,4-dimethoxyphenyl)-5-(6-(pyrrolidin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-morpholinophenyl)-5-(6-(pyrrolidin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(3,4-dimethoxyphenyl)-N-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-(4-methylpiperazin-1-yl)phenyl)-5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1H-indazol-6-yl)-5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 6-((5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2H-benzo[b][1,4]oxazin-3(4H)-one; 5-phenyl-N-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-phenyl-N-(4-(pyrrolidin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(3,4-dimethoxyphenyl)-N-(1H-indazol-5-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(3,4-dimethoxyphenyl)-N-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(3,4-dimethoxyphenyl)-N-(4-(pyrrolidin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1H-pyrazol-3-yl)-5-(pyridin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(pyridin-4-yl)-N-(4-(pyrrolidin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N,5-di(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-(4-methylpiperazin-1-yl)phenyl)-5-(6-(pyrrolidin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 6-((5-(6-(pyrrolidin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2H-benzo[b][1,4]oxazin-3(4H)-one; N-(1H-pyrazol-3-yl)-5-(6-(pyrrolidin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-(pyrrolidin-1-yl)phenyl)-5-(6-(pyrrolidin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1H-indazol-5-yl)-5-(1-methylpiperidin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3,4-dimethoxyphenyl)-5-(1-methylpiperidin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(1-methylpiperidin-4-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-(4-methylpiperazin-1-yl)phenyl)-5-(1-methylpiperidin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 6-((5-(1-methylpiperidin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2H-benzo[b][1,4]oxazin-3(4H)-one; 5-(1-methylpiperidin-4-yl)-N-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(1-methylpiperidin-4-yl)-N-(4-(pyrrolidin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(5-cyclopropyl-1H-pyrazol-3-yl)-5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3,4-dimethoxyphenyl)-5-(4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(4-methoxyphenyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3,4-dimethoxyphenyl)-5-(3-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(3-methoxyphenyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(3-methoxyphenyl)-N-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N1-(5-(3-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-N4,N4-dimethylbenzene-1,4-diamine; N-(5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-amine; 3-((5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenol; 5-(4-methoxyphenyl)-N-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1H-indazol-6-yl)-5-(3-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3,4-dimethoxyphenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-morpholinophenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-(4-methylpiperazin-1-yl)phenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N1,N1-dimethyl-N4-(5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)benzene-1,4-diamine; N-(3,4-dimethoxyphenyl)-5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-morpholinophenyl)-5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-(4-methylpiperazin-1-yl)phenyl)-5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N1,N1-dimethyl-N4-(5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)benzene-1,4-diamine; N-(1H-indazol-6-yl)-5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(5-cyclopropyl-1H-pyrazol-3-yl)-5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N1-(5-(4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-N4,N4-dimethylbenzene-1,4-diamine; N-(1H-indazol-6-yl)-5-(4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 3-((5-(4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenol; 3-((5-(3-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenol; N-(1H-indazol-6-yl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 3-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenol; N-(5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-amine; 3-((5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenol; N-(5-cyclopropyl-1H-pyrazol-3-yl)-5-(4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(5-(4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-amine; N-(5-cyclopropyl-1H-pyrazol-3-yl)-5-(3-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(5-(3-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-amine; N-(5-cyclopropyl-1H-pyrazol-3-yl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-amine; N-(5-cyclopropyl-1H-pyrazol-3-yl)-5-(1-methylpiperidin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(5-(1-methylpiperidin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-amine; 3-((5-(1-methylpiperidin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenol; 5-(benzo[d]thiazol-2-yl)-N-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(benzo[d]thiazol-2-yl)-N-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(5-(benzo[d]thiazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-amine; 5-(benzo[d]thiazol-2-yl)-N-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-(4-methylpiperazin-1-yl)phenyl)-5-(3-(pyridin-3-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(5-cyclopropyl-1H-pyrazol-3-yl)-5-(3-(pyridin-3-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3,4-dimethoxyphenyl)-5-(3-(pyridin-3-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-morpholinophenyl)-5-(3-(pyridin-3-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(5-(3-(pyridin-3-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-amine; N-(1H-indazol-6-yl)-5-(3-(pyridin-3-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 2-(7-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenol; N-(4-(4-methylpiperazin-1-yl)phenyl)-5-(3-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3,4-dimethoxyphenyl)-5-(3-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(2-methoxyphenyl)-N-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3,4-dimethoxyphenyl)-5-(2-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(5-(2-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-amine; N-(1H-indazol-6-yl)-5-(2-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(2-methoxyphenyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(5-cyclopropyl-1H-pyrazol-3-yl)-5-(2-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N1,N1-dimethyl-N3-(5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)benzene-1,3-diamine; N1-(5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)cyclohexane-1,2-diamine; N1-(5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)benzene-1,3-diamine; N-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-(4-ethylpiperazin-1-yl)phenyl)-5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-((dimethylamino)methyl)phenyl)-5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(2,5-dimethoxyphenyl)-N-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(2,5-dimethoxyphenyl)-N-(4-(4-ethylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-(4-cyclopropylpiperazin-1-yl)phenyl)-5-(2,5-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(2-aminoethyl)-3-(7-((4-morpholinophenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzamide; N-(3,4-dimethoxyphenyl)-5-(imidazo[1,2-a]pyridin-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-(4-ethylpiperazin-1-yl)phenyl)-5-(imidazo[1,2-a]pyridin-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(imidazo[1,2-a]pyridin-2-yl)-N-(1H-indazol-5-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(imidazo[1,2-a]pyridin-2-yl)-N-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 4-((5-(imidazo[1,2-a]pyridin-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)benzoic acid; 5-(1H-benzo[d]imidazol-2-yl)-N-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3,4-dimethoxyphenyl)-5-(1-methyl-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(3-methoxyphenyl)-N-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(3-methoxyphenyl)-N-(4-(pyrrolidin-1-ylmethyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-((5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)-3-(m-tolyl)urea; (4-methylpiperazin-1-yl)(4-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)methanone; pyrrolidin-1-yl(4-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)methanone; N-(4-thiomorpholinophenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 4-(4-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)thiomorpholine 1,1-dioxide; 1-(4-(4-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one; (3-methoxy-4-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)(4-(4-methylpiperazin-1-yl)piperidin-1-yl)methanone; 5-(1H-imidazol-5-yl)-N-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(1H-imidazol-2-yl)-N-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; pyrrolidin-1-yl(4-((5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)methanone; 4-(4-((5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)thiomorpholine 1,1-dioxide; 1-(4-(4-((5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one; N-(4-thiomorpholinophenyl)-5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 6-((5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2H-benzo[b][1,4]oxazin-3(4H)-one; (4-methylpiperazin-1-yl)(4-((5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)methanone; 2,2-dimethyl-N-(5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-3,4-dihydro-2H-benzo[b][1,4]thiazin-6-amine; 5-(3-(2H-tetrazol-5-yl)phenyl)-N-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; (7-((2-(dimethylamino)ethyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)(phenyl)methanone; (7-(((1-methylpiperidin-4-yl)methyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)(phenyl)methanone; (7-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)(phenyl)methanone; (7-((3,4-dimethoxyphenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)(phenyl)methanone; (4-((5-benzoyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)(pyrrolidin-1-yl)methanone; 7-((5-benzoyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3,4-dihydroquinolin-2(1H)-one; 3-(7-((4-morpholinophenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoic acid; morpholino(4-((5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)methanone; 6-((5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2H-benzo[b][1,4]thiazin-3(4H)-one; 7-((5-(4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3,4-dihydroquinolin-2(1H)-one; (4-((5-(4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)(pyrrolidin-1-yl)methanone; N-(4-(4-(tert-butyl)piperazin-1-yl)phenyl)-5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 6-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2H-benzo[b][1,4]oxazin-3(4H)-one; N-(4-(4-(tert-butyl)piperazin-1-yl)phenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 8-((5-(4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-4,5-dihydro-1H-benzo[b]azepin-2(3H)-one; 6-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2H-benzo[b][1,4]thiazin-3(4H)-one; 1-methyl-N-(5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-1,2,3,4-tetrahydroquinolin-7-amine; 2-methyl-2-(4-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)propanenitrile; 5-(4-methoxyphenyl)-N-(4-thiomorpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 4-(4-((5-(4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)thiomorpholine 1,1-dioxide; 1-(4-(4-((5-(4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one; 6-((5-(4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2H-benzo[b][1,4]oxazin-3(4H)-one; N-(4-(4-(tert-butyl)piperazin-1-yl)phenyl)-5-(4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 2,2-dimethyl-N-(5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-3,4-dihydro-2H-benzo[b][1,4]thiazin-6-amine; 2-(3-(7-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenoxy)acetic acid; 5-(7-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)thiophene-3-carboxylic acid; 2-(3-(7-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)acetic acid; 6-(7-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)picolinic acid; N-(4-(pentafluorosulfanyl)phenyl)-5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-(4-methylpiperazin-1-yl)phenyl)-5-(thiazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(3-(((4-methylbenzyl)amino)methyl)phenyl)-N-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(3-(3-(dimethylamino)propoxy)phenyl)-N-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 3-(7-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide; 3-(7-((3,4-dimethoxyphenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide; 1-(4-(4-((5-(thiazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one; N-(3,4-dimethoxyphenyl)-5-(thiazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 7-((5-(thiazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3,4-dihydroquinolin-2(1H)-one; N-(3-(7-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide; N-(3-(7-((4-(piperazin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide; N-(3-(7-((3,4-dimethoxyphenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide; N-(3-(7-((2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide; N-(3-(7-((4-(4-acetylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide; 1-(4-(4-((5-(3-(2H-tetrazol-5-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one; 5-(3-(2H-tetrazol-5-yl)phenyl)-N-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 3-(7-((3,4-dimethoxyphenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoic acid; 3-(7-((2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoic acid; 7-((5-(3-(2H-tetrazol-5-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3,4-dihydroquinolin-2(1H)-one; N-(4-(4-methylpiperazin-1-yl)phenyl)-5-(thiazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-(thiazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one; N-(3,4-dimethoxyphenyl)-5-(thiazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-(4-methylpiperazin-1-yl)phenyl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one; N-(3,4-dimethoxyphenyl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-(4-methylpiperazin-1-yl)phenyl)-5-(oxazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-(oxazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one; N-(3,4-dimethoxyphenyl)-5-(oxazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 7-((5-(thiazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3,4-dihydroquinolin-2(1H)-one; 7-((5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3,4-dihydroquinolin-2(1H)-one; 7-((5-(oxazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3,4-dihydroquinolin-2(1H)-one; N-(4-(1-methylpiperidin-4-yl)phenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; methyl 3-(7-((2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate; methyl 3-(7-((3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate; 3-(7-((3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoic acid; methyl 4-(7-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate; methyl 4-(7-((3,4-dimethoxyphenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate; methyl 4-(7-((2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate; methyl 3-(7-((3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazin-6-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate; methyl 3-(7-((2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-8-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate; 3-(7-((2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-8-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoic acid; N-(3,4-dimethoxyphenyl)-5-(3-(pentafluorosulfanyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(3-(pentafluorosulfanyl)phenyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-(4-methylpiperazin-1-yl)phenyl)-5-(3-(pentafluorosulfanyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 7-((5-(3-(pentafluorosulfanyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3,4-dihydroquinolin-2(1H)-one; N-(3,4-dimethoxyphenyl)-5-(3-(methylthio)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(3-(methylthio)phenyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-(4-methylpiperazin-1-yl)phenyl)-5-(3-(methylthio)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3,4-dimethoxyphenyl)-5-(3-(trifluoromethoxy)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-morpholinophenyl)-5-(3-(trifluoromethoxy)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3,4-dimethoxyphenyl)-5-(3-(trifluoromethyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-morpholinophenyl)-5-(3-(trifluoromethyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(3-chlorophenyl)-N-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(3-chlorophenyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3,4-dimethoxyphenyl)-5-(2-fluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(2-fluorophenyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3,4-dimethoxyphenyl)-5-(3-fluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(3-fluorophenyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 7-((5-(3-(methylthio)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3,4-dihydroquinolin-2(1H)-one; 3-(7-((4-(4-acetylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide; 3-(7-((2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide; 3-(7-((4-morpholinophenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide; 3-(7-((3-methoxy-4-morpholinophenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide; 4-(7-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoic acid; methyl 4-(7-((4-morpholinophenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate; 4-(7-((4-morpholinophenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoic acid; 4-(7-((3,4-dimethoxyphenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoic acid; N-(2-methyl-1H-benzo[d]imidazol-5-yl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 1-(4-(4-((5-(3-(methylsulfonyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one; 5-(1H-indazol-6-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(1H-indazol-6-yl)-N-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3,4-dimethoxyphenyl)-5-(3-(methylsulfonyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 7-((5-(3-(methylsulfonyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3,4-dihydroquinolin-2(1H)-one; 5-(3-(methylsulfonyl)phenyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(2-methyl-1H-benzo[d]imidazol-5-yl)-5-(3-(methylsulfonyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N,5-bis(3-(methylsulfonyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3-(methylsulfonyl)phenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 2-((3-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)sulfonyl)ethan-1-ol; 1-(4-(4-((5-(1H-pyrrolo[3,2-b]pyridin-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one; 7-((5-(1H-pyrrolo[3,2-b]pyridin-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3,4-dihydroquinolin-2(1H)-one; N-(4-morpholinophenyl)-5-(1H-pyrrolo[3,2-b]pyridin-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(2-methyl-1H-benzo[d]imidazol-5-yl)-5-(1H-pyrrolo[3,2-b]pyridin-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N,N-dimethyl-4-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)benzenesulfonamide; N-cyclopropyl-3-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)benzenesulfonamide; N-(3-(2H-1,2,3-triazol-2-yl)phenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-(2H-1,2,3-triazol-2-yl)phenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N,N-dimethyl-3-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)benzenesulfonamide; N-methyl-3-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)benzenesulfonamide; N-(3-(morpholinosulfonyl)phenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(thiophen-2-yl)-N-(3-((trifluoromethyl)sulfonyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3-(methylsulfinyl)phenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 7-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3,4-dihydroquinolin-2(1H)-one; N-(3,4-dimethoxyphenyl)-5-(4-fluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(4-fluorophenyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(3,4-difluorophenyl)-N-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(3,4-difluorophenyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(3,5-difluorophenyl)-N-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(2-fluorophenyl)-N-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(2-fluorophenyl)-N-(3-(methylsulfonyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(2-fluorophenyl)-N-(2-(methylsulfonyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(2-fluorophenyl)-N-(4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-(4-cyclopropylpiperazin-1-yl)phenyl)-5-(2-fluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3,4-dimethoxyphenyl)-5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(2,6-difluorophenyl)-N-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(2,6-difluorophenyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-(4-cyclopropylpiperazin-1-yl)phenyl)-5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(2,6-difluorophenyl)-N-(4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(2,4-difluorophenyl)-N-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(2,4-difluorophenyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 6-(7-((2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one; 6-(7-((4-morpholinophenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one; 6-(7-((2-methyl-1H-benzo[d]imidazol-5-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one; N-(4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(2-(methylsulfonyl)phenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3-((dimethylamino)methyl)phenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-(4-cyclopropylpiperazin-1-yl)phenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; morpholino(4-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)methanone; N-(4-(morpholinomethyl)phenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3-fluoro-4-morpholinophenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; (4-(4-methylpiperazin-1-yl)piperidin-1-yl)(4-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)methanone; 6-(7-((4-(4-acetylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one; 6-(7-((3,4-dimethoxyphenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one; 5-(3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-N-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 5-(3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-N-(2-methyl-1H-benzo[d]imidazol-5-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(2-methylisoindolin-5-yl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(1,3-dihydroisobenzofuran-5-yl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3-(tert-butyl)phenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; methyl 3-(7-((4-(4-acetylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate; methyl 3-(7-((1H-indazol-6-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate; methyl 3-(7-((4-morpholinophenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate; 5-(3-aminophenyl)-N-(4-((dimethylamino)methyl)phenyl)-1H-pyrazolo[4,3-d]Pyrimidin-7-amine; 5-(2-fluorophenyl)-N-(2-methylisoindolin-5-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(4-((dimethylamino)methyl)phenyl)-5-(2-fluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; N-(3-((dimethylamino)methyl)phenyl)-5-(2-fluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine.

14. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable ester, hydrate, solvate or salt thereof, optionally in combination with a pharmaceutically acceptable carrier.

15. A method of treatment of a disease mediated by kinase-activity comprising the administration, to a patient in need thereof, of a therapeutically effective amount of a compound according to claim 1, wherein the disease is selected from the group consisting of pruritus, eczema, asthma, rhinitis, dry eye, ocular inflammation, allergic conjunctivitis, vernal conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, fungal keratitis, uveitis, chronic lymphocytic leukemia, B-cell lymphoma, rheumatoid arthritis, thrombosis, graft versus host, inflammatory arthritis and other immune-mediated inflammatory diseases, systemic lupus erythematosus, immune thrombocytopenic purpura, and auto-immune hemolytic anemia.

16. The method according to claim 15, wherein said treatment is systemic.

17. The method according to claim 15, wherein said administration is topical.

18. The method according to claim 17, wherein said topical administration is to the skin.

19. The method according to claim 17, wherein said topical administration is to the eye.

20. The method according to claim 17, wherein said topical administration is intranasal or by inhalation.

21. A method of treatment of a disease mediated by kinase-activity comprising the administration, to a patient in need thereof, of a therapeutically effective amount of a pharmaceutical composition of claim 14, wherein the disease is selected from the group consisting of pruritus, eczema, asthma, rhinitis, dry eye, ocular inflammation, allergic conjunctivitis, vernal conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, fungal keratitis, uveitis, chronic lymphocytic leukemia, B-cell lymphoma, rheumatoid arthritis, thrombosis, graft versus host, inflammatory arthritis and other immune-mediated inflammatory diseases, systemic lupus erythematosus, immune thrombocytopenic purpura, and auto-immune hemolytic anemia.

22. The method according to claim 21, wherein said treatment is systemic.

23. The method according to claim 21, wherein said administration is topical.

24. The method according to claim 21, wherein said topical administration is to the skin.

25. The method according to claim 21, wherein said topical administration is to the eye.

26. The method according to claim 21, wherein said topical administration is intranasal or by inhalation.

Description

EXAMPLES

Materials and Methods

(1) Biological Assays—Protein Kinase Assays

(2) SYK Assay

(3) In the assay OMNIA® KINASE ASSAY by Invitrogen Corporation (Carlsbad) the effect of invention of a compound on the phosphorylation is determined by measurement of fluorescence intensity of a chelation-enhanced fluorophore called SOX. Upon phosphorylation of the peptide by the kinase of interest, Mg2+ is chelated to form a bridge between the SOX moiety and the phosphate group that is transferred to the specific tyrosine on the peptide. The fluorescence intensity is directly proportional to the amount of peptide phosphorylation.

(4) To the wells of an 384 well small volume plate (Greiner, Frickenhausen) are added (i) the compound under test in 5% DMSO/distilled water (2 μl), (ii) 16 μl of the master mix containing ATP, DTT, Kinase Reaction Buffer, Omina Peptide Substrate Tyr 7 resulting in a final concentration of 1 mM ATP, 0.2 mM DTT and 10 μM Peptide Substrate.

(5) The Master Mix and the assay plate was incubated to reaction temperature before the measurement (30° C.). The reaction was started with addition of (iii) 2 μl 4 μg/ml SYK kinase (Invitrogen, Carlsbad). During measurement fluorescence intensitiy readings were collected using a TECAN M1000 at a wavelength of λex 360/λem 485 nm every 30 s for 30 minutes. The reaction velocity was plotted versus the inhibitor concentration to determine the 1050 using XLFit 5.0 (IDBS, Guildford) to fit to a sigmoidal dose response curve, and the apparent Ki values were calculated from the IC50 using the Cheng-Prusoff equation (Cheng, Y.; Prusoff, W. H. Biochem. Pharmacol. 22, 3099-3108, 1973).

(6) The ATP dependency was determined according to Lai C-J-, Wu J C A Simple Kinetic Method for Rapid Mechanistic Analysis of Reversible Enzyme Inhibitors. Assays and Drug Dev. Technologies. 2003; 1(4):527-535. To demonstrate a competition effect of the test compounds towards ATP the corresponding test compound was used at the 50% inhibitory concentration. Assay conditions as described previously were maintained. ATP concentrations used was 1000, 333, 100, 33.3, 10, 3.3, 1 μM.

(7) LRRK2-LRRK2 G2019S-Assay

(8) In the assay LanthaScreen™ Eu Kinase Binding Assay by Invitrogen Corporation (Carlsbad) the effect of invention of a compound on the phosphorylation is determined by measurement of fluorescence intensity emission ratio based on the binding and displacement of a proprietary, Alexa Fluor® 647-labeled, ATP-competitive kinase inhibitor scaffold (kinase tracer) to the kinase of interest. Binding of the tracer to the kinase is detected using a europium-labeled anti-tag antibody, which binds to the kinase of interest. Simultaneous binding of both the tracer and antibody to the kinase results in a high degree of FRET (fluorescence resonance energy transfer) from the europium (Eu) donor fluorophore to the Alexa Fluor® 647 acceptor fluorophore on the kinase tracer. Binding of an inhibitor to the kinase competes for binding with the tracer, resulting in a loss of FRET. The fluorescence intensity ratio is directly proportional to the amount of peptide phosphorylation.

(9) To the wells of an 384 well small volume plate (Greiner, Frickenhausen) are added (i) the compound under test in 5% DMSO/distilled water (5 μl), (ii) 5 μl of the kinase antibody mixture resulting in a final concentration 5 nM LRRK2 or their mutants, 2 nM EU-Anti-GST antibody in 1× kinase buffer A. The reaction was started with addition of (iii) 5 μl resulting in a final concentration of 10 nM tracer 236. The assay plate was incubated at RT for 1 h and fluorescence intensitiy readings were collected using a TECAN M1000 at two wavelengthes of λex 340/λem 615 nm and λex 340/λm 665 nm with a delay time of 100 μs and an integration time of 200 μs after 60 minutes. The emission ratio was calculated by division of the acceptor/tracer emission (665 nM) by the antibody/donor emission (615 nM). The inhibitor concentration was plotted versus the emission ratio to determine the IC50 using XLFit 5.0 (IDBS, Guildford) to fit to a sigmoidal dose response curve with a variable slope.

(10) MYLK Assay

(11) In the assay LanthaScreen™ Eu Kinase Binding Assay by Invitrogen Corporation (Carlsbad) the effect of invention of a compound on the phosphorylation is determined by measurement of fluorescence intensity emission ratio based on the binding and displacement of a proprietary, Alexa Fluor® 647-labeled, ATP-competitive kinase inhibitor scaffold (kinase tracer) to the kinase of interest as described above.

(12) To the wells of an 384 well small volume plate (Greiner, Frickenhausen) are added (i) the compound under test in 5% is DMSO/distilled water (5 μl), (ii) 5 μl of the kinase antibody mixture resulting in a final concentration 5 nM MYLK, 2 nM EU-Anti-GST antibody in 1× kinase buffer A. The reaction was started with addition of (iii) 5 μl resulting in a final concentration of 30 nM tracer 236. The assay plate was incubated at RT for 1 h and fluorescence intensity readings were collected using a TECAN M1000 at two wavelengths of λex 340/λem 615 nm and λex 340/λem 665 nm with a delay time of 100 μs and an integration time of 200 μs after 60 minutes. The emission ratio was calculated by division of the acceptor/tracer emission (665 nM) by the antibody/donor emission (615 nM). The inhibitor concentration was plotted versus the emission ratio to determine the IC50 using XLFit 5.0 (IDBS, Guildford) to fit to a sigmoidal dose response curve with a variable slope.

(13) Biological Assays—Cellular Assay

(14) LAD2 Assay

(15) The inhibition of Syk may also be determined by examining IgE mediated release of histamine in vitro using human conjunctival tissue mast cells or in LAD2 mast cells (Leuk Res. 2003 Aug. 27(8):677-82). Human conjunctival tissue mast cells (HCTMCs) are obtained using the methodology outlined in U.S. Pat. No. 5,360,720, for example. Briefly, HCTMCs are enzymatically released from human conjunctival tissues and then partially enriched by density centrifugation over a PERCOLL® cushion. A monodispersed cell suspension is obtained from the resulting pellet, and these cells are used for a histamine release assay. Cells are exposed to drug or control prior to stimulation with anti-human IgE, which triggers mast cell degranulation and histamine release to the supernatant. Histamine is then measured in the supernatant by EIA (Beckman Coulter), RIA (Beckman Coulter) or other method known to one of skill in the art. A decrease in histamine release drug treated cells indicates that the compound has potential for further investigation.

(16) The LAD2 mast cell line is used in much the same way with the exception that the cells are passively sensitized with human IgE myeloma prior to stimulation with anti-human IgE to cross-link receptor bound IgE and trigger degranulation.

(17) General Procedures for Synthesis of Compounds

(18) Chromatography

(19) The compound verification via analytical HPLC-MS was done after purification using the following instrumentation, column and method:

(20) Analytical method for compound purity

(21) Instrumentation:

(22) Agilent MSD 1100

(23) Analytical Methods:

(24) Solvents:

(25) A: acetonitrile

(26) B: H2O

(27) C: 2% HCOOH in acetonitrile

(28) D: 0.1% NEt3 in acetonitrile

(29) The following analytical methods were used:

(30) Method A

(31) Column SunFire C18 from Waters 2.1×50 mm 2.5 μm particle size,

(32) thermostated @ 40°

(33) Gradient:

(34) TABLE-US-00001 Time [min] % B % C % D Flow [mL/min] 0 90 5 0 0.6 2.5 10 5 0 0.6 4 10 5 0 0.6 4.5 90 5 0 0.6 6 90 5 0 0.6
Stop time @ 7 min
MS: ESI positive, Mass scan from 100 to 800
gradient fragmentation: 50 to 125V
UV: detection @ 220 and 254 nm
Method B
Column ODS-AQ from YMC 4.0×50 mm 2.5 μm particle size,
thermostated @ RT
Gradient:

(35) TABLE-US-00002 Time [min] % B % C % D Flow [mL/min] 0 90 5 0 1.3 2.5 10 5 0 1.3 4 10 5 0 1.3 4.5 90 5 0 1.3 6 90 5 0 1.3
Stop time @ 7 min
MS: ESI positive, Mass scan from 100 to 800
gradient fragmentation: 50 to 125V
UV: detection @ 220 and 254 nm
Method C
Column ODS-AQ from YMC 2.1×50 mm 3 μm particle size,
thermostated @ 40° C.
Gradient:

(36) TABLE-US-00003 Time [min] % B % C % D Flow [mL/min] 0 90 5 0 0.6 2.5 10 5 0 0.6 4 10 5 0 0.6 4.5 90 5 0 0.6 6 90 5 0 0.6
Stop time @ 7 min
MS: ESI positive, Mass scan from 100 to 800
gradient fragmentation: 50 to 125V
UV: detection @ 220 and 254 nm
Method D
Column ODS-AQ from YMC 2.1×50 mm 3 μm particle size, incl. GuardCol 2.1×10 mm, 3 μm particle size
thermostated 40° C.
Gradient:

(37) TABLE-US-00004 Time [min] % B % C % D Flow [mL/min] 0 90 5 0 0.6 10.0 10 5 0 0.6 13.0 10 5 0 0.6 14.0 90 5 0 0.6
Stop time @ 15 min
MS: ESI positive, Mass scan from 100 to 800
gradient fragmentation: 50 to 125V
UV: detection @ 220 and 254 nm
Method E
Column ODS-AQ from YMC 2.1×50 mm 3 μm particle size,
thermostated @ 40° C.
Gradient:

(38) TABLE-US-00005 Time [min] % B % C % D Flow [mL/min] 0 90 5 0 0.6 5.0 10 5 0 0.6 7.0 10 5 0 0.6 8.0 90 5 0 0.6
Stop time @ 10 min
MS: ESI positive, Mass scan from 100 to 800
gradient fragmentation: 50 to 125V
UV: detection @ 220 and 254 nm
Method F
Column SunFire C18 from Waters 2.1×50 mm 2.5 μm particle size,
thermostated @ 40°
Gradient:

(39) TABLE-US-00006 Time [min] % B % C % D Flow [mL/min] 0 90 5 0 1.2 7.0 10 5 0 1.2 8.5 10 5 0 1.2 9.0 90 5 0 1.2 11.0 90 5 0 1.2
Stop time @ 12 min
MS: ESI positive, Mass scan from 100 to 800
gradient fragmentation: 50 to 125V
UV: detection @ 220 and 254 nm
Method G
Column YMC C8 OS 4.0×50 mm 4 μm particle size,
thermostated @ 40°
Gradient:

(40) TABLE-US-00007 Time [min] % B % C % D Flow [mL/min] 0 90 5 0 1.5 2.5 10 5 0 1.5 4.0 10 5 0 1.5 4.5 90 5 0 1.5 6.0 90 5 0 1.5
Stop time @ 6 min
MS: ESI positive, Mass scan from 100 to 800
gradient fragmentation: 50 to 125V
UV: detection @ 220 and 254 nm
Method H
Column Waters XBridge C18 2.1×50 mm 2.5 μm particle size,
thermostated @ 40°
Gradient:

(41) TABLE-US-00008 Time [min] % B % C % D Flow [mL/min] 0 90 5 0 0.55 2.5 10 5 0 0.55 4.0 10 5 0 0.55 4.5 90 5 0 0.55 6.0 90 5 0 0.55
Stop time @ 6 min
MS: ESI positive, Mass scan from 100 to 800
gradient fragmentation: 50 to 125V
UV: detection @ 220 and 254 nm
Method I
Column Waters XBridge C18 2.1×50 mm 2.5 μm particle size,
thermostated @ 40°
Gradient:

(42) TABLE-US-00009 Time [min] % B % C % D Flow [mL/min] 0 90 0 5 0.55 2.5 10 0 5 0.55 4.0 10 0 5 0.55 4.5 90 0 5 0.55 6.0 90 0 5 0.55
Stop time @ 6 min
MS: ESI positive, Mass scan from 100 to 800
gradient fragmentation: 50 to 125V
UV: detection @ 220 and 254 nm
Method J
Column Waters SunFire C18 2.1×50 mm, 2.5 μm particle size
thermostated@40° C.
Gradient:

(43) TABLE-US-00010 Time[min] % B % C % D Flow[mL/min] 0 90 5 0 0.6 10 10 5 0 0.6 13 10 5 0 0.6 14 90 5 0 0.6
Stop time@15 min
MS: ESI positive, Mass scan from 100 to 800
gradient fragmentation: 50 to 125V
UV: detection @ 220 and 254 nm
Method K
Column YMC ODS-AQ 2.1×50 mm, 3 μm particle size
incl. GuardCol 2.1×10 mm, 3 μm particle size
thermostated@40° C.
Gradient:

(44) TABLE-US-00011 Time[min] % B % C % D Flow[mL/min] 0 99 5 0 0.6 2.5 10 5 0 0.6 4 10 5 0 0.6 4.5 99 5 0 0.6 6 99 5 0 0.6
Stop time@7 min
MS: ESI positive, Mass scan from 100 to 800
gradient fragmentation: 50 to 125V
UV: detection @ 220 and 254 nm
Method L
Column YMC TriArt C18 2.0×50 mm, 1.9 μm, #TA12SP90502WT
thermostated@40° C.
Gradient:

(45) TABLE-US-00012 Time[min] % B % C % D Flow[mL/min] 0 90 5 0 0.45 0.5 90 5 0 0.45 4.5 10 5 0 0.45 5.5 10 5 0 0.45 5.6 90 5 0 0.45
Stop time@10 min
MS: ESI positive, Mass scan from 100 to 800
gradient fragmentation: 50 to 125V
UV: detection @ 220 and 254 nm
Purification and Characterisation:

(46) The resulting crude reaction products were purified in an automatic process using a semi-preparative HPLC-MS with mass-triggered sampling of the desired peak:

(47) Purification Via Semi-Preparative HPLC-MS

(48) Instrumentation:

(49) 2× Varian PrepStar SD-1

(50) 1× Dionex P580 Pump 1 Channel (MakeUP I)

(51) 1× Dionex AXP-MS (MakeUP II)

(52) 1× Dionex MSQ

(53) 1× Dionex UVD 340V-Prep Flow Cell

(54) Gilson 215 Liquid Handler

(55) Column:

(56) SunFire Prep C18 OBD 5 μm 19×50 mm

(57) Method:

(58) Column Flow: 30 ml/min

(59) Solvent A: methanol, 0.3% acetic acid

(60) Solvent B: water, 0.3% acetic acid

(61) Time Table for Gradient:

(62) TABLE-US-00013 Time (min) Solv. A Solv. B 0.0 30.00 70.00 10.0 100.00 0.00 14.0 100.00 0.00 14.4 30.00 70.00 16.4 30.00 70.00
Detection:
UV 254 nm, Mass Spectrometer Detector (API-ES, positive)
Compound Preparation

(63) Where the preparation of starting materials is not described, these are commercially available, known in the literature, or readily obtainable by those skilled in the art using standard procedures. Where it is stated that compounds were prepared analogously to earlier examples or intermediates, it will be appreciated by the skilled person that the reaction time, number of equivalents of reagents and temperature can be modified for each specific reaction and that it may be necessary or desirable to employ different workup or purification techniques. Where reactions are carried out using microwave irradiation, the microwave used is an Initiator 60 supplied by Biotage. The actual power supplied varies during the course of the reaction in order to maintain a constant temperature.

(64) Abbreviations

(65) DCM=Dichloromethane

(66) DMF=N,N-Dimethylformamide

(67) DDQ=2,3-Dichloro-5,6-dicyano-1,4-benzoquinone

(68) THF=Tetrahydrofuran

(69) MeOH=Methanol

(70) TFA=Trifluoroacetic acid

(71) TEA=Triethylamine

(72) rm=Reaction mixture

(73) rt=Room temperature

(74) AcOH=Acetic acid

(75) MeCN=Acetonitrile

(76) EtOH=Ethanol

(77) EtOAc=Ethyl Acetate

(78) LCMS=Mass spectrometry directed high pressure liquid chromatography

(79) UV=Ultraviolet

(80) DMSO=Dimethylsulphoxide

(81) Intermediates

Preparation of 7-chloro-2-(4-methoxybenzyl)-5-phenyl-2H-pyrazolo[4,3-d]pyrimidine

Step 1: 5-Phenyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one

(82) 4-Amino-2H-pyrazole-3-carboxylic acid amide (5 mmol) and benzaldehyde (5 mmol) were dissolved in acetic acid (14 ml). Subsequently DDQ (3.75 mmol) were added and the reaction mixture is heated in the microwave to 180° C. for 30 minutes. The precipitate was filtered and washed with Et2O.

(83) Mexact=212,079

(84) Yield 80%

(85) HPLC-MS method: A

(86) Retention Time: 2.1 min

(87) mass found (m+H): 213.1

Step 2: Protection of Pyrazole with 1-Chloromethyl-4-methoxy-benzene

(88) 5-Phenyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one (3.9 mmol) was dissolved in 14 ml acetonitrile. 1-Chloromethyl-4-methoxy-benzene (4.7 mmol), 1.2 eq triethylamine (4.7 mmol) and sodiumiodide (0.39 mmol) was added subsequently. The reaction mixture was heated in the microwave for 30 min at 160° C. After cooling down the reaction the resulting precipitate was filtered and washed with Et2O.

(89) The reaction is leading to two isomers (1-(4-Methoxy-benzyl)-5-phenyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one and 2-(4-Methoxy-benzyl)-5-phenyl-2,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one).

(90) Both isomers can be used for the next steps.

(91) Yield: 47%

(92) Mexact=332,149

(93) HPLC-MS method: A

(94) Retention time: 2.96 min/3.2 min (Isomers)

(95) Mass found (m+H): 333.1

Step 3: Chlorination

(96) The mixture of 1-(4-Methoxy-benzyl)-5-phenyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one and 2-(4-Methoxy-benzyl)-5-phenyl-2,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one (0.18 mmol) was suspended in POCl3. The mixture was heated to 100° C. in a reaction vessel. After 0.5 h-24 h LC-MS showed reaction completion. The mixture was cooled to rt. The mixture was concentrated to dryness, cooled to 0° C., and quenched with ice/water. The mixture was extracted with DCM. The organic layer was washed with NaHCO3 sat. aq. and water, dried (Na2SO4) filtered and concentrated.

(97) The product was used without further purification.

(98) The product is an isomeric mixture of 7-Chloro-1-(4-methoxy-benzyl)-5-phenyl-1H-pyrazolo[4,3-d]pyrimidine and 7-Chloro-2-(4-methoxy-benzyl)-5-phenyl-2H-pyrazolo[4,3-d]pyrimidine

(99) Both isomers can be used for the next steps.

(100) Mexact=350,113

(101) HPLC-MS method: A

(102) Retention time: 3.98 min/4.3 min

(103) Mass found (m+H): 351.1

(104) The following Chlorides and Isomers were synthesized according the above mentioned procedure:

(105) 7-chloro-2-(4-methoxybenzyl)-5-phenyl-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-2-(4-methoxybenzyl)-5-(pyridin-4-yl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-2-(4-methoxybenzyl)-5-(6-(pyrrolidin-1-yl)pyridin-3-yl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-5-(3,4-dimethoxyphenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-2-(4-methoxybenzyl)-5-(1-methylpiperidin-4-yl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-2-(4-methoxybenzyl)-5-(1H-pyrazol-3-yl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-2-(4-methoxybenzyl)-5-(4-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-2-(4-methoxybenzyl)-5-(3-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-3-yl)-2H-pyrazolo[4,3-d]pyrimidine; 2-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzo[d]thiazole; 7-chloro-2-(4-methoxybenzyl)-5-(3-(pyridin-3-yl)phenyl)-2H-pyrazolo[4,3-d]pyrimidine; 2-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)phenol; 4-(3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)morpholine; 7-chloro-2-(4-methoxybenzyl)-5-(2-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-5-(2,5-dimethoxyphenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; N-(2-aminoethyl)-3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzamide; 7-chloro-5-(imidazo[1,2-a]pyridin-2-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; 5-(1H-benzo[d]imidazol-2-yl)-7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-2-(4-methoxybenzyl)-5-(1-methyl-1H-benzo[d]imidazol-2-yl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-5-(1H-imidazol-5-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-5-(1H-imidazol-2-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; 5-(3-(2H-tetrazol-5-yl)phenyl)-7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; (7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)(phenyl)methanone; 3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoic acid methyl ester; 2-(3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)phenoxy)acetic acid methyl ester; 5-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)thiophene-3-carboxylic acid methyl ester; 2-(3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)acetic acid methyl ester; 6-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)picolinic acid methyl ester; 2-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)thiazole; N-(3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzyl)-1-(p-tolyl)methanamine; 3-(3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)phenoxy)-N,N-dimethylpropan-1-amine; 3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide; N-(3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide; 4-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)thiazole; 4-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)oxazole; 2-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)oxazole; methyl 3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate; methyl 4-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate; 7-chloro-5-(3-(pentafluorosulfanyl)phenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-2-(4-methoxybenzyl)-5-(3-(methylthio)phenyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-2-(4-methoxybenzyl)-5-(3-(trifluoromethoxy)phenyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-2-(4-methoxybenzyl)-5-(3-(trifluoromethyl)phenyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-5-(3-chlorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-5-(2-fluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-5-(3-fluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; 4-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoic acid methyl ester; 7-chloro-2-(4-methoxybenzyl)-5-(3-(methylsulfonyl)phenyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-5-(1H-indazol-6-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-2-(4-methoxybenzyl)-5-(1H-pyrrolo[3,2-b]pyridin-6-yl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-5-(4-fluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-5-(3,4-difluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-5-(3,5-difluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-5-(2,6-difluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-chloro-5-(2,4-difluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine; 7-Chloro-2-(4-methoxy-benzyl)-5-(3-nitro-phenyl)-2H-pyrazolo[4,3-d]pyrimidine; 6-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one;

Example #1

Preparation of N-(1H-indazol-5-yl)-5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(106) 7-chloro-2-(4-methoxybenzyl)-5-phenyl-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1H-indazol-5-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(107) exact mass: 327.1386 g/mol

(108) HPLC-MS: analytical method A

(109) rt: 2.194 min-found mass: 328 (m/z+H)

Example #2

Preparation of N-(1H-benzo[d][1,2,3]triazol-5-yl)-5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(110) 7-chloro-2-(4-methoxybenzyl)-5-phenyl-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1H-benzo[d][1,2,3]triazol-5-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(111) exact mass: 328.1316 g/mol

(112) HPLC-MS: analytical method A

(113) rt: 2.336 min-found mass: 329 (m/z+H)

Example #3

Preparation of 5-phenyl-N-(4-(piperidin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(114) 7-chloro-2-(4-methoxybenzyl)-5-phenyl-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(piperidin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(115) exact mass: 370.2241 g/mol

(116) HPLC-MS: analytical method A

(117) rt: 2.245 min-found mass: 371 (m/z+H)

Example #4

Preparation of N1,N1-dimethyl-N4-(5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)benzene-1,4-diamine

(118) 7-chloro-2-(4-methoxybenzyl)-5-phenyl-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and N1,N1-dimethylbenzene-1,4-diamine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(119) exact mass: 330.1856 g/mol

(120) HPLC-MS: analytical method I

(121) rt: 3.175 min-found mass: 331 (m/z+H)

Example #5

Preparation of 3-((5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)benzamide

(122) 7-chloro-2-(4-methoxybenzyl)-5-phenyl-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3-aminobenzamide (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(123) exact mass: 330.1405 g/mol

(124) HPLC-MS: analytical method A

(125) rt: 2.290 min-found mass: 331 (m/z+H)

Example #6

Preparation of N-(3,4-dimethoxyphenyl)-5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(126) 7-chloro-2-(4-methoxybenzyl)-5-phenyl-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL).

(127) The reaction mixture was irradiated in a microwave reactor for min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(128) exact mass: 347.1618 g/mol

(129) HPLC-MS: analytical method A

(130) rt: 2.544 min-found mass: 348 (m/z+H)

Example #7

Preparation of N-(4-morpholinophenyl)-5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(131) 7-chloro-2-(4-methoxybenzyl)-5-phenyl-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(132) exact mass: 372.199 g/mol

(133) HPLC-MS: analytical method A

(134) rt: 2.546 min-found mass: 373 (m/z+H)

Example #8

Preparation of N-(3-methoxyphenyl)-5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(135) 7-chloro-2-(4-methoxybenzyl)-5-phenyl-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3-methoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(136) exact mass: 317.1479 g/mol

(137) HPLC-MS: analytical method A

(138) rt: 2.867 min-found mass: 318 (m/z+H)

Example #9

Preparation of N-(2-methyl-1H-benzo[d]imidazol-5-yl)-5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(139) 7-chloro-2-(4-methoxybenzyl)-5-phenyl-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 2-methyl-1H-benzo[d]imidazol-5-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(140) exact mass: 341.1581 g/mol

(141) HPLC-MS: analytical method I

(142) rt: 2.576 min-found mass: 342 (m/z+H)

Example #10

Preparation of 4-((5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)benzoic-acid

(143) 7-chloro-2-(4-methoxybenzyl)-5-phenyl-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-aminobenzoic-acid (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(144) exact mass: 331.1224 g/mol

(145) HPLC-MS: analytical method A

(146) rt: 2.581 min-found mass: 332 (m/z+H)

Example #11

Preparation of 4-((5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)benzamide

(147) 7-chloro-2-(4-methoxybenzyl)-5-phenyl-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-aminobenzamide (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(148) exact mass: 330.1405 g/mol

(149) HPLC-MS: analytical method A

(150) rt: 2.287 min-found mass: 331 (m/z+H)

Example #12

Preparation of 4-((5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)benzonitrile

(151) 7-chloro-2-(4-methoxybenzyl)-5-phenyl-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-aminobenzonitrile (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(152) exact mass: 312.126 g/mol

(153) HPLC-MS: analytical method A

(154) rt: 3.081 min-found mass: 313 (m/z+H)

Example #13

Preparation of N-(1H-indazol-5-yl)-5-(pyridin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(155) 7-chloro-2-(4-methoxybenzyl)-5-(pyridin-4-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1H-indazol-5-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(156) exact mass: 328.1316 g/mol

(157) HPLC-MS: analytical method A

(158) rt: 1.850 min-found mass: 329 (m/z+H)

Example #14

Preparation of N-(1H-indazol-5-yl)-5-(6-(pyrrolidin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(159) 7-chloro-2-(4-methoxybenzyl)-5-(6-(pyrrolidin-1-yl)pyridin-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1H-indazol-5-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(160) exact mass: 397.2021 g/mol

(161) HPLC-MS: analytical method A

(162) rt: 2.011 min-found mass: 398 (m/z+H)

Example #15

Preparation of 2-((5-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)benzamide

(163) 7-chloro-5-(3,4-dimethoxyphenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 2-aminobenzamide (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(164) exact mass: 390.1682 g/mol

(165) HPLC-MS: analytical method A

(166) rt: 1.960 min-found mass: 391 (m/z+H)

Example #16

Preparation of N-(1H-indazol-6-yl)-5-(pyridin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(167) 7-chloro-2-(4-methoxybenzyl)-5-(pyridin-4-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1H-indazol-6-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(168) exact mass: 328.1316 g/mol

(169) HPLC-MS: analytical method A

(170) rt: 1.935 min-found mass: 329 (m/z+H)

Example #17

Preparation of N1,N1-dimethyl-N4-(5-(pyridin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)benzene-1,4-diamine

(171) 7-chloro-2-(4-methoxybenzyl)-5-(pyridin-4-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and N1,N1-dimethylbenzene-1,4-diamine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(172) exact mass: 331.1786 g/mol

(173) HPLC-MS: analytical method A

(174) rt: 0.678 min-found mass: 332 (m/z+H)

Example #18

Preparation of N-(3,4-dimethoxyphenyl)-5-(pyridin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(175) 7-chloro-2-(4-methoxybenzyl)-5-(pyridin-4-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(176) exact mass: 348.1548 g/mol

(177) HPLC-MS: analytical method A

(178) rt: 2.013 min-found mass: 349 (m/z+H)

Example #19

Preparation of N-(4-morpholinophenyl)-5-(pyridin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(179) 7-chloro-2-(4-methoxybenzyl)-5-(pyridin-4-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(180) exact mass: 373.192 g/mol

(181) HPLC-MS: analytical method A

(182) rt: 1.974 min-found mass: 374 (m/z+H)

Example #20

Preparation of N-(4-(4-methylpiperazin-1-yl)phenyl)-5-(pyridin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(183) 7-chloro-2-(4-methoxybenzyl)-5-(pyridin-4-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(184) exact mass: 386.2296 g/mol

(185) HPLC-MS: analytical method A

(186) rt: 0.504 min-found mass: 387 (m/z+H)

Example #21

Preparation of 6-((5-(pyridin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2H-benzo[b][1,4]oxazin-3(4H)-one

(187) 7-chloro-2-(4-methoxybenzyl)-5-(pyridin-4-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 6-amino-2H-benzo[b][1,4]oxazin-3(4H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(188) exact mass: 359.1274 g/mol

(189) HPLC-MS: analytical method A

(190) rt: 1.930 min-found mass: 360 (m/z+H)

Example #22

Preparation of 5-(3,4-dimethoxyphenyl)-N-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(191) 7-chloro-5-(3,4-dimethoxyphenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1H-indazol-6-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(192) exact mass: 387.1664 g/mol

(193) HPLC-MS: analytical method A

(194) rt: 2.233 min-found mass: 388 (m/z+H)

Example #23

Preparation of N1-(5-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-N4,N4-dimethylbenzene-1,4-diamine

(195) 7-chloro-5-(3,4-dimethoxyphenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and N1,N1-dimethylbenzene-1,4-diamine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(196) exact mass: 390.2133 g/mol

(197) HPLC-MS: analytical method A

(198) rt: 2.173 min-found mass: 391 (m/z+H)

Example #24

Preparation of N,5-bis(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(199) 7-chloro-5-(3,4-dimethoxyphenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(200) exact mass: 407.1896 g/mol

(201) HPLC-MS: analytical method A

(202) rt: 2.303 min-found mass: 408 (m/z+H)

Example #25

Preparation of 5-(3,4-dimethoxyphenyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(203) 7-chloro-5-(3,4-dimethoxyphenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(204) exact mass: 432.2267 g/mol

(205) HPLC-MS: analytical method A

(206) rt: 2.282 min-found mass: 433 (m/z+H)

Example #26

Preparation of 6-((5-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2H-benzo[b][1,4]oxazin-3(4H)-one

(207) 7-chloro-5-(3,4-dimethoxyphenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 6-amino-2H-benzo[b][1,4]oxazin-3(4H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(208) exact mass: 418.1621 g/mol

(209) HPLC-MS: analytical method A

(210) rt: 2.218 min-found mass: 419 (m/z+H)

Example #27

Preparation of N-(1H-indazol-6-yl)-5-(1-methylpiperidin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(211) 7-chloro-2-(4-methoxybenzyl)-5-(1-methylpiperidin-4-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1H-indazol-6-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(212) exact mass: 348.211 g/mol

(213) HPLC-MS: analytical method A

(214) rt: 0.486 min-found mass: 349 (m/z+H)

Example #28

Preparation of N1,N1-dimethyl-N4-(5-(1-methylpiperidin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)benzene-1,4-diamine

(215) 7-chloro-2-(4-methoxybenzyl)-5-(1-methylpiperidin-4-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and N1,N1-dimethylbenzene-1,4-diamine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(216) exact mass: 351.258 g/mol

(217) HPLC-MS: analytical method A

(218) rt: 0.293 min-found mass: 352 (m/z+H)

Example #29

Preparation of N-(4-chlorophenyl)-5-(1-methylpiperidin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(219) 7-chloro-2-(4-methoxybenzyl)-5-(1-methylpiperidin-4-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-chloroaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(220) exact mass: 342.1648 g/mol

(221) HPLC-MS: analytical method A

(222) rt: 0.935 min-found mass: 343 (m/z+H)

Example #30

Preparation of N-(1H-indazol-6-yl)-5-(6-(pyrrolidin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(223) 7-chloro-2-(4-methoxybenzyl)-5-(6-(pyrrolidin-1-yl)pyridin-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1H-indazol-6-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(224) exact mass: 397.2021 g/mol

(225) HPLC-MS: analytical method A

(226) rt: 2.060 min-found mass: 398 (m/z+H)

Example #31

Preparation of N1,N1-dimethyl-N4-(5-(6-(pyrrolidin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)benzene-1,4-diamine

(227) 7-chloro-2-(4-methoxybenzyl)-5-(6-(pyrrolidin-1-yl)pyridin-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and N1,N1-dimethylbenzene-1,4-diamine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(228) exact mass: 400.2491 g/mol

(229) HPLC-MS: analytical method A

(230) rt: 1.890 min-found mass: 401 (m/z+H)

Example #32

Preparation of N-(3,4-dimethoxyphenyl)-5-(6-(pyrrolidin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(231) 7-chloro-2-(4-methoxybenzyl)-5-(6-(pyrrolidin-1-yl)pyridin-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(232) exact mass: 417.2253 g/mol

(233) HPLC-MS: analytical method I

(234) rt: 2.551 min-found mass: 418 (m/z+H)

Example #33

Preparation of N-(4-morpholinophenyl)-5-(6-(pyrrolidin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(235) 7-chloro-2-(4-methoxybenzyl)-5-(6-(pyrrolidin-1-yl)pyridin-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(236) exact mass: 442.2624 g/mol

(237) HPLC-MS: analytical method I

(238) rt: 2.553 min-found mass: 443 (m/z+H)

Example #34

Preparation of 5-(3,4-dimethoxyphenyl)-N-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(239) 7-chloro-5-(3,4-dimethoxyphenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(240) exact mass: 445.2643 g/mol

(241) HPLC-MS: analytical method A

(242) rt: 1.761 min-found mass: 446 (m/z+H)

Example #35

Preparation of N-(4-(4-methylpiperazin-1-yl)phenyl)-5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(243) 7-chloro-2-(4-methoxybenzyl)-5-phenyl-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(244) exact mass: 385.2366 g/mol

(245) HPLC-MS: analytical method I

(246) rt: 2.028 min-found mass: 386 (m/z+H)

Example #36

Preparation of N-(1H-indazol-6-yl)-5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(247) 7-chloro-2-(4-methoxybenzyl)-5-phenyl-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1H-indazol-6-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(248) exact mass: 327.1386 g/mol

(249) HPLC-MS: analytical method A

(250) rt: 2.428 min-found mass: 328 (m/z+H)

Example #37

Preparation of 6-((5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2H-benzo[b][1,4]oxazin-3(4H)-one

(251) 7-chloro-2-(4-methoxybenzyl)-5-phenyl-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 6-amino-2H-benzo[b][1,4]oxazin-3(4H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(252) exact mass: 358.1344 g/mol

(253) HPLC-MS: analytical method A

(254) rt: 2.390 min-found mass: 359 (m/z+H)

Example #38

Preparation of 5-phenyl-N-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(255) 7-chloro-2-(4-methoxybenzyl)-5-phenyl-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1H-pyrazol-3-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(256) exact mass: 277.1205 g/mol

(257) HPLC-MS: analytical method A

(258) rt: 2.202 min-found mass: 278 (m/z+H)

Example #39

Preparation of 5-phenyl-N-(4-(pyrrolidin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(259) 7-chloro-2-(4-methoxybenzyl)-5-phenyl-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(pyrrolidin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(260) exact mass: 356.2046 g/mol

(261) HPLC-MS: analytical method A

(262) rt: 2.714 min-found mass: 357 (m/z+H)

Example #40

Preparation of 5-(3,4-dimethoxyphenyl)-N-(1H-indazol-5-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(263) 7-chloro-5-(3,4-dimethoxyphenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1H-indazol-5-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(264) exact mass: 387.1664 g/mol

(265) HPLC-MS: analytical method A

(266) rt: 2.102 min-found mass: 388 (m/z+H)

Example #41

Preparation of 5-(3,4-dimethoxyphenyl)-N-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(267) 7-chloro-5-(3,4-dimethoxyphenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1H-pyrazol-3-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(268) exact mass: 337.1483 g/mol

(269) HPLC-MS: analytical method A

(270) rt: 2.046 min-found mass: 338 (m/z+H)

Example #42

Preparation of 5-(3,4-dimethoxyphenyl)-N-(4-(pyrrolidin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(271) 7-chloro-5-(3,4-dimethoxyphenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(pyrrolidin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(272) exact mass: 416.2323 g/mol

(273) HPLC-MS: analytical method A

(274) rt: 2.560 min-found mass: 417 (m/z+H)

Example #43

Preparation of N-(1H-pyrazol-3-yl)-5-(pyridin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(275) 7-chloro-2-(4-methoxybenzyl)-5-(pyridin-4-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1H-pyrazol-3-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(276) exact mass: 278.1135 g/mol

(277) HPLC-MS: analytical method A

(278) rt: 0.823 min-found mass: 279 (m/z+H)

Example #44

Preparation of 5-(pyridin-4-yl)-N-(4-(pyrrolidin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(279) 7-chloro-2-(4-methoxybenzyl)-5-(pyridin-4-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(pyrrolidin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(280) exact mass: 357.1976 g/mol

(281) HPLC-MS: analytical method A

(282) rt: 2.138 min-found mass: 358 (m/z+H)

Example #45

Preparation of N,5-di(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(283) 7-chloro-2-(4-methoxybenzyl)-5-(1H-pyrazol-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1H-pyrazol-3-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(284) exact mass: 267.1069 g/mol

(285) HPLC-MS: analytical method A

(286) rt: 0.817 min-found mass: 268 (m/z+H)

Example #46

Preparation of N-(4-(4-methylpiperazin-1-yl)phenyl)-5-(6-(pyrrolidin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(287) 7-chloro-2-(4-methoxybenzyl)-5-(6-(pyrrolidin-1-yl)pyridin-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(288) exact mass: 455.3001 g/mol

(289) HPLC-MS: analytical method A

(290) rt: 1.038 min-found mass: 456 (m/z+H)

Example #47

Preparation of 6-((5-(6-(pyrrolidin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2H-benzo[b][1,4]oxazin-3(4H)-one

(291) 7-chloro-2-(4-methoxybenzyl)-5-(6-(pyrrolidin-1-yl)pyridin-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 6-amino-2H-benzo[b][1,4]oxazin-3(4H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(292) exact mass: 428.1979 g/mol

(293) HPLC-MS: analytical method A

(294) rt: 2.047 min-found mass: 429 (m/z+H)

Example #48

Preparation of N-(1H-pyrazol-3-yl)-5-(6-(pyrrolidin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(295) 7-chloro-2-(4-methoxybenzyl)-5-(6-(pyrrolidin-1-yl)pyridin-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1H-pyrazol-3-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(296) exact mass: 347.184 g/mol

(297) HPLC-MS: analytical method A

(298) rt: 1.867 min-found mass: 348 (m/z+H)

Example #49

Preparation of N-(4-(pyrrolidin-1-yl)phenyl)-5-(6-(pyrrolidin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(299) 7-chloro-2-(4-methoxybenzyl)-5-(6-(pyrrolidin-1-yl)pyridin-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(pyrrolidin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(300) exact mass: 426.2681 g/mol

(301) HPLC-MS: analytical method A

(302) rt: 2.326 min-found mass: 427 (m/z+H)

Example #50

Preparation of N-(1H-indazol-5-yl)-5-(1-methylpiperidin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(303) 7-chloro-2-(4-methoxybenzyl)-5-(1-methylpiperidin-4-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1H-indazol-5-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(304) exact mass: 348.211 g/mol

(305) HPLC-MS: analytical method I

(306) rt: 0.465 min-found mass: 349 (m/z+H)

Example #51

Preparation of N-(3,4-dimethoxyphenyl)-5-(1-methylpiperidin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(307) 7-chloro-2-(4-methoxybenzyl)-5-(1-methylpiperidin-4-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(308) exact mass: 368.2343 g/mol

(309) HPLC-MS: analytical method I

(310) rt: 0.331 min-found mass: 369 (m/z+H)

Example #52

Preparation of 5-(1-methylpiperidin-4-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(311) 7-chloro-2-(4-methoxybenzyl)-5-(1-methylpiperidin-4-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(312) exact mass: 393.2714 g/mol

(313) HPLC-MS: analytical method I

(314) rt: 0.331 min-found mass: 394 (m/z+H)

Example #53

Preparation of N-(4-(4-methylpiperazin-1-yl)phenyl)-5-(1-methylpiperidin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(315) 7-chloro-2-(4-methoxybenzyl)-5-(1-methylpiperidin-4-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(316) exact mass: 406.309 g/mol

(317) HPLC-MS: analytical method I

(318) rt: 0.326 min-found mass: 407 (m/z+H)

Example #54

Preparation of 6-((5-(1-methylpiperidin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2H-benzo[b][1,4]oxazin-3(4H)-one

(319) 7-chloro-2-(4-methoxybenzyl)-5-(1-methylpiperidin-4-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 6-amino-2H-benzo[b][1,4]oxazin-3(4H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(320) exact mass: 379.2068 g/mol

(321) HPLC-MS: analytical method I

(322) rt: 0.331 min-found mass: 380 (m/z+H)

Example #55

Preparation of 5-(1-methylpiperidin-4-yl)-N-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(323) 7-chloro-2-(4-methoxybenzyl)-5-(1-methylpiperidin-4-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1H-pyrazol-3-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(324) exact mass: 298.193 g/mol

(325) HPLC-MS: analytical method I

(326) rt: 0.344 min-found mass: 299 (m/z+H)

Example #56

Preparation of 5-(1-methylpiperidin-4-yl)-N-(4-(pyrrolidin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(327) 7-chloro-2-(4-methoxybenzyl)-5-(1-methylpiperidin-4-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(pyrrolidin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(328) exact mass: 377.277 g/mol

(329) HPLC-MS: analytical method I

(330) rt: 2.282 min-found mass: 378 (m/z+H)

Example #57

Preparation of N-(5-cyclopropyl-1H-pyrazol-3-yl)-5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(331) 7-chloro-2-(4-methoxybenzyl)-5-phenyl-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 5-cyclopropyl-1H-pyrazol-3-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(332) exact mass: 317.159 g/mol

(333) HPLC-MS: analytical method A

(334) rt: 2.540 min-found mass: 318 (m/z+H)

Example #58

Preparation of N-(3,4-dimethoxyphenyl)-5-(4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(335) 7-chloro-2-(4-methoxybenzyl)-5-(4-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(336) exact mass: 377.1757 g/mol

(337) HPLC-MS: analytical method A

(338) rt: 2.386 min-found mass: 378 (m/z+H)

Example #59

Preparation of 5-(4-methoxyphenyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(339) 7-chloro-2-(4-methoxybenzyl)-5-(4-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(340) exact mass: 402.2128 g/mol

(341) HPLC-MS: analytical method A

(342) rt: 2.336 min-found mass: 403 (m/z+H)

Example #60

Preparation of N-(3,4-dimethoxyphenyl)-5-(3-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(343) 7-chloro-2-(4-methoxybenzyl)-5-(3-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(344) exact mass: 377.1757 g/mol

(345) HPLC-MS: analytical method A

(346) rt: 2.561 min-found mass: 378 (m/z+H)

Example #61

Preparation of 5-(3-methoxyphenyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(347) 7-chloro-2-(4-methoxybenzyl)-5-(3-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(348) exact mass: 402.2128 g/mol

(349) HPLC-MS: analytical method A

(350) rt: 2.487 min-found mass: 403 (m/z+H)

Example #62

Preparation of 5-(3-methoxyphenyl)-N-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(351) 7-chloro-2-(4-methoxybenzyl)-5-(3-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(352) exact mass: 415.2504 g/mol

(353) HPLC-MS: analytical method B

(354) rt: 1.631 min-found mass: 416 (m/z+H)

Example #63

Preparation of N1-(5-(3-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-N4,N4-dimethylbenzene-1,4-diamine

(355) 7-chloro-2-(4-methoxybenzyl)-5-(3-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and N1,N1-dimethylbenzene-1,4-diamine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(356) exact mass: 360.1994 g/mol

(357) HPLC-MS: analytical method A

(358) rt: 2.312 min-found mass: 361 (m/z+H)

Example #64

Preparation of N-(5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-amine

(359) 7-chloro-2-(4-methoxybenzyl)-5-phenyl-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dihydro-2H-benzo[b][1,4]oxazin-6-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(360) exact mass: 344.16 g/mol

(361) HPLC-MS: analytical method A

(362) rt: 2.358 min-found mass: 345 (m/z+H)

Example #65

Preparation of 3-((5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenol

(363) 7-chloro-2-(4-methoxybenzyl)-5-phenyl-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3-aminophenol (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(364) exact mass: 303.1284 g/mol

(365) HPLC-MS: analytical method A

(366) rt: 2.408 min-found mass: 304 (m/z+H)

Example #66

Preparation of 5-(4-methoxyphenyl)-N-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(367) 7-chloro-2-(4-methoxybenzyl)-5-(4-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(368) exact mass: 415.2504 g/mol

(369) HPLC-MS: analytical method B

(370) rt: 1.540 min-found mass: 416 (m/z+H)

Example #67

Preparation of N-(1H-indazol-6-yl)-5-(3-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(371) 7-chloro-2-(4-methoxybenzyl)-5-(3-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1H-indazol-6-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(372) exact mass: 357.1524 g/mol

(373) HPLC-MS: analytical method A

(374) rt: 2.485 min-found mass: 358 (m/z+H)

Example #68

Preparation of N-(3,4-dimethoxyphenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(375) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(376) exact mass: 353.1143 g/mol

(377) HPLC-MS: analytical method A

(378) rt: 2.541 min-found mass: 354 (m/z+H)

Example #69

Preparation of N-(4-morpholinophenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(379) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(380) exact mass: 378.1515 g/mol

(381) HPLC-MS: analytical method A

(382) rt: 2.497 min-found mass: 379 (m/z+H)

Example #70

Preparation of N-(4-(4-methylpiperazin-1-yl)phenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(383) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(384) exact mass: 391.1891 g/mol

(385) HPLC-MS: analytical method B

(386) rt: 1.587 min-found mass: 392 (m/z+H)

Example #71

Preparation of N1,N1-dimethyl-N4-(5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)benzene-1,4-diamine

(387) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and N1,N1-dimethylbenzene-1,4-diamine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(388) exact mass: 336.138 g/mol

(389) HPLC-MS: analytical method A

(390) rt: 2.230 min-found mass: 337 (m/z+H)

Example #72

Preparation of N-(3,4-dimethoxyphenyl)-5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(391) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(392) exact mass: 353.1143 g/mol

(393) HPLC-MS: analytical method A

(394) rt: 2.319 min-found mass: 354 (m/z+H)

Example #73

Preparation of N-(4-morpholinophenyl)-5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(395) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(396) exact mass: 378.1515 g/mol

(397) HPLC-MS: analytical method A

(398) rt: 2.288 min-found mass: 379 (m/z+H)

Example #74

Preparation of N-(4-(4-methylpiperazin-1-yl)phenyl)-5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(399) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(400) exact mass: 391.1891 g/mol

(401) HPLC-MS: analytical method B

(402) rt: 1.478 min-found mass: 392 (m/z+H)

Example #75

Preparation of N1,N1-dimethyl-N4-(5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)benzene-1,4-diamine

(403) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and N1,N1-dimethylbenzene-1,4-diamine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(404) exact mass: 336.138 g/mol

(405) HPLC-MS: analytical method A

(406) rt: 2.121 min-found mass: 337 (m/z+H)

Example #76

Preparation of N-(1H-indazol-6-yl)-5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(407) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1H-indazol-6-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(408) exact mass: 333.091 g/mol

(409) HPLC-MS: analytical method A

(410) rt: 2.242 min-found mass: 334 (m/z+H)

Example #77

Preparation of N-(5-cyclopropyl-1H-pyrazol-3-yl)-5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(411) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 5-cyclopropyl-1H-pyrazol-3-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(412) exact mass: 323.1115 g/mol

(413) HPLC-MS: analytical method A

(414) rt: 2.379 min-found mass: 324 (m/z+H)

Example #78

Preparation of N1-(5-(4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-N4,N4-dimethylbenzene-1,4-diamine

(415) 7-chloro-2-(4-methoxybenzyl)-5-(4-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and N1,N1-dimethylbenzene-1,4-diamine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(416) exact mass: 360.1994 g/mol

(417) HPLC-MS: analytical method A

(418) rt: 2.244 min-found mass: 361 (m/z+H)

Example #79

Preparation of N-(1H-indazol-6-yl)-5-(4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(419) 7-chloro-2-(4-methoxybenzyl)-5-(4-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1H-indazol-6-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(420) exact mass: 357.1524 g/mol

(421) HPLC-MS: analytical method A

(422) rt: 2.294 min-found mass: 358 (m/z+H)

Example #80

Preparation of 3-((5-(4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenol

(423) 7-chloro-2-(4-methoxybenzyl)-5-(4-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3-aminophenol (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(424) exact mass: 333.1423 g/mol

(425) HPLC-MS: analytical method A

(426) rt: 2.253 min-found mass: 334 (m/z+H)

Example #81

Preparation of 3-((5-(3-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenol

(427) 7-chloro-2-(4-methoxybenzyl)-5-(3-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3-aminophenol (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(428) exact mass: 333.1423 g/mol

(429) HPLC-MS: analytical method A

(430) rt: 2.486 min-found mass: 334 (m/z+H)

Example #82

Preparation of N-(1H-indazol-6-yl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(431) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1H-indazol-6-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(432) exact mass: 333.091 g/mol

(433) HPLC-MS: analytical method A

(434) rt: 2.463 min-found mass: 334 (m/z+H)

Example #83

Preparation of 3-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenol

(435) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3-aminophenol (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(436) exact mass: 309.0809 g/mol

(437) HPLC-MS: analytical method A

(438) rt: 2.441 min-found mass: 310 (m/z+H)

Example #84

Preparation of N-(5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-amine

(439) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dihydro-2H-benzo[b][1,4]oxazin-6-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(440) exact mass: 350.1124 g/mol

(441) HPLC-MS: analytical method A

(442) rt: 2.255 min-found mass: 351 (m/z+H)

Example #85

Preparation of 3-((5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenol

(443) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3-aminophenol (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(444) exact mass: 309.0809 g/mol

(445) HPLC-MS: analytical method A

(446) rt: 2.255 min-found mass: 310 (m/z+H)

Example #86

Preparation of N-(5-cyclopropyl-1H-pyrazol-3-yl)-5-(4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(447) 7-chloro-2-(4-methoxybenzyl)-5-(4-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 5-cyclopropyl-1H-pyrazol-3-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(448) exact mass: 347.1729 g/mol

(449) HPLC-MS: analytical method A

(450) rt: 2.412 min-found mass: 348 (m/z+H)

Example #87

Preparation of N-(5-(4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-amine

(451) 7-chloro-2-(4-methoxybenzyl)-5-(4-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dihydro-2H-benzo[b][1,4]oxazin-6-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(452) exact mass: 374.1738 g/mol

(453) HPLC-MS: analytical method A

(454) rt: 2.296 min-found mass: 375 (m/z+H)

Example #88

Preparation of N-(5-cyclopropyl-1H-pyrazol-3-yl)-5-(3-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(455) 7-chloro-2-(4-methoxybenzyl)-5-(3-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 5-cyclopropyl-1H-pyrazol-3-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(456) exact mass: 347.1729 g/mol

(457) HPLC-MS: analytical method A

(458) rt: 2.604 min-found mass: 348 (m/z+H)

Example #89

Preparation of N-(5-(3-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-amine

(459) 7-chloro-2-(4-methoxybenzyl)-5-(3-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dihydro-2H-benzo[b][1,4]oxazin-6-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(460) exact mass: 374.1738 g/mol

(461) HPLC-MS: analytical method A

(462) rt: 2.434 min-found mass: 375 (m/z+H)

Example #90

Preparation of N-(5-cyclopropyl-1H-pyrazol-3-yl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(463) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 5-cyclopropyl-1H-pyrazol-3-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(464) exact mass: 323.1115 g/mol

(465) HPLC-MS: analytical method F

(466) rt: 5.010 min-found mass: 324 (m/z+H)

Example #91

Preparation of N-(5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-amine

(467) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dihydro-2H-benzo[b][1,4]oxazin-6-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(468) exact mass: 350.1124 g/mol

(469) HPLC-MS: analytical method A

(470) rt: 2.425 min-found mass: 351 (m/z+H)

Example #92

Preparation of N-(5-cyclopropyl-1H-pyrazol-3-yl)-5-(1-methylpiperidin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(471) 7-chloro-2-(4-methoxybenzyl)-5-(1-methylpiperidin-4-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 5-cyclopropyl-1H-pyrazol-3-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(472) exact mass: 338.2315 g/mol

(473) HPLC-MS: analytical method A

(474) rt: 0.330 min-found mass: 339 (m/z+H)

Example #93

Preparation of N-(5-(1-methylpiperidin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-amine

(475) 7-chloro-2-(4-methoxybenzyl)-5-(1-methylpiperidin-4-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dihydro-2H-benzo[b][1,4]oxazin-6-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(476) exact mass: 365.2325 g/mol

(477) HPLC-MS: analytical method A

(478) rt: 0.321 min-found mass: 366 (m/z+H)

Example #94

Preparation of 3-((5-(1-methylpiperidin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenol

(479) 7-chloro-2-(4-methoxybenzyl)-5-(1-methylpiperidin-4-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3-aminophenol (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(480) exact mass: 324.2009 g/mol

(481) HPLC-MS: analytical method A

(482) rt: 0.308 min-found mass: 325 (m/z+H)

Example #95

Preparation of 5-(benzo[d]thiazol-2-yl)-N-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(483) 2-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzo[d]thiazole (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(484) exact mass: 442.2001 g/mol

(485) HPLC-MS: analytical method A

(486) rt: 2.111 min-found mass: 443 (m/z+H)

Example #96

Preparation of 5-(benzo[d]thiazol-2-yl)-N-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(487) 2-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzo[d]thiazole (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(488) exact mass: 404.1254 g/mol

(489) HPLC-MS: analytical method A

(490) rt: 3.058 min-found mass: 405 (m/z+H)

Example #97

Preparation of N-(5-(benzo[d]thiazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-amine

(491) 2-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzo[d]thiazole (0.16 mmol) and 3,4-dihydro-2H-benzo[b][1,4]oxazin-6-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(492) exact mass: 401.1235 g/mol

(493) HPLC-MS: analytical method A

(494) rt: 2.909 min-found mass: 402 (m/z+H)

Example #98

Preparation of 5-(benzo[d]thiazol-2-yl)-N-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(495) 2-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzo[d]thiazole (0.16 mmol) and 1H-indazol-6-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(496) exact mass: 384.1021 g/mol

(497) HPLC-MS: analytical method C

(498) rt: 2.360 min-found mass: 385 (m/z+H)

Example #99

Preparation of N-(4-(4-methylpiperazin-1-yl)phenyl)-5-(3-(pyridin-3-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(499) 7-chloro-2-(4-methoxybenzyl)-5-(3-(pyridin-3-yl)phenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(500) exact mass: 462.2667 g/mol

(501) HPLC-MS: analytical method A

(502) rt: 1.861 min-found mass: 463 (m/z+H)

Example #100

Preparation of N-(5-cyclopropyl-1H-pyrazol-3-yl)-5-(3-(pyridin-3-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(503) 7-chloro-2-(4-methoxybenzyl)-5-(3-(pyridin-3-yl)phenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 5-cyclopropyl-1H-pyrazol-3-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(504) exact mass: 394.1891 g/mol

(505) HPLC-MS: analytical method A

(506) rt: 2.318 min-found mass: 395 (m/z+H)

Example #101

Preparation of N-(3,4-dimethoxyphenyl)-5-(3-(pyridin-3-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(507) 7-chloro-2-(4-methoxybenzyl)-5-(3-(pyridin-3-yl)phenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(508) exact mass: 424.1919 g/mol

(509) HPLC-MS: analytical method A

(510) rt: 2.349 min-found mass: 425 (m/z+H)

Example #102

Preparation of N-(4-morpholinophenyl)-5-(3-(pyridin-3-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(511) 7-chloro-2-(4-methoxybenzyl)-5-(3-(pyridin-3-yl)phenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(512) exact mass: 449.2291 g/mol

(513) HPLC-MS: analytical method A

(514) rt: 2.299 min-found mass: 450 (m/z+H)

Example #103

Preparation of N-(5-(3-(pyridin-3-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-amine

(515) 7-chloro-2-(4-methoxybenzyl)-5-(3-(pyridin-3-yl)phenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dihydro-2H-benzo[b][1,4]oxazin-6-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(516) exact mass: 421.1901 g/mol

(517) HPLC-MS: analytical method A

(518) rt: 2.218 min-found mass: 422 (m/z+H)

Example #104

Preparation of N-(1H-indazol-6-yl)-5-(3-(pyridin-3-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(519) 7-chloro-2-(4-methoxybenzyl)-5-(3-(pyridin-3-yl)phenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1H-indazol-6-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(520) exact mass: 404.1687 g/mol

(521) HPLC-MS: analytical method A

(522) rt: 2.238 min-found mass: 405 (m/z+H)

Example #105

Preparation of 2-(7-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenol

(523) 2-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)phenol (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(524) exact mass: 401.231 g/mol

(525) HPLC-MS: analytical method A

(526) rt: 2.011 min-found mass: 402 (m/z+H)

Example #106

Preparation of N-(4-(4-methylpiperazin-1-yl)phenyl)-5-(3-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(527) 4-(3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)morpholine (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(528) exact mass: 470.3015 g/mol

(529) HPLC-MS: analytical method A

(530) rt: 1.793 min-found mass: 471 (m/z+H)

Example #107

Preparation of N-(3,4-dimethoxyphenyl)-5-(3-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(531) 4-(3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)morpholine (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(532) exact mass: 432.2267 g/mol

(533) HPLC-MS: analytical method A

(534) rt: 2.410 min-found mass: 433 (m/z+H)

Example #108

Preparation of 5-(2-methoxyphenyl)-N-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(535) 7-chloro-2-(4-methoxybenzyl)-5-(2-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(536) exact mass: 415.2504 g/mol

(537) HPLC-MS: analytical method A

(538) rt: 1.338 min-found mass: 416 (m/z+H)

Example #109

Preparation of N-(3,4-dimethoxyphenyl)-5-(2-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(539) 7-chloro-2-(4-methoxybenzyl)-5-(2-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(540) exact mass: 377.1757 g/mol

(541) HPLC-MS: analytical method A

(542) rt: 2.215 min-found mass: 378 (m/z+H)

Example #110

Preparation of N-(5-(2-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-amine

(543) 7-chloro-2-(4-methoxybenzyl)-5-(2-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dihydro-2H-benzo[b][1,4]oxazin-6-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(544) exact mass: 374.1738 g/mol

(545) HPLC-MS: analytical method A

(546) rt: 2.227 min-found mass: 375 (m/z+H)

Example #111

Preparation of N-(1H-indazol-6-yl)-5-(2-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(547) 7-chloro-2-(4-methoxybenzyl)-5-(2-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1H-indazol-6-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(548) exact mass: 357.1524 g/mol

(549) HPLC-MS: analytical method A

(550) rt: 2.125 min-found mass: 358 (m/z+H)

Example #112

Preparation of 5-(2-methoxyphenyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(551) 7-chloro-2-(4-methoxybenzyl)-5-(2-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(552) exact mass: 402.2128 g/mol

(553) HPLC-MS: analytical method A

(554) rt: 2.252 min-found mass: 403 (m/z+H)

Example #113

Preparation of N-(5-cyclopropyl-1H-pyrazol-3-yl)-5-(2-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(555) 7-chloro-2-(4-methoxybenzyl)-5-(2-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 5-cyclopropyl-1H-pyrazol-3-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(556) exact mass: 347.1729 g/mol

(557) HPLC-MS: analytical method A

(558) rt: 2.242 min-found mass: 348 (m/z+H)

Example #114

Preparation of N1,N1-dimethyl-N3-(5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)benzene-1,3-diamine

(559) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and N1,N1-dimethylbenzene-1,3-diamine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(560) exact mass: 336.138 g/mol

(561) HPLC-MS: analytical method C

(562) rt: 2.085 min-found mass: 337 (m/z+H)

Example #115

Preparation of (1R,2R)—N-(5-Thiophen-3-yl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-cyclohexane-1,2-diamine

(563) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and ((1R,2R)-2-Amino-cyclohexyl)-carbamic acid tert-butyl ester (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(564) exact mass: 314.159 g/mol

(565) HPLC-MS: analytical method C

(566) rt: 1.411 min-found mass: 315 (m/z+H)

Example #116

Preparation of (1S,2R)—N-(5-Thiophen-3-yl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-cyclohexane-1,2-diamine

(567) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and ((1S,2R)-2-Amino-cyclohexyl)-carbamic acid tert-butyl ester (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(568) exact mass: 314.159 g/mol

(569) HPLC-MS: analytical method C

(570) rt: 1.388 min-found mass: 315 (m/z+H)

Example #117

Preparation of N1-(5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)benzene-1,3-diamine

(571) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and benzene-1,3-diamine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(572) exact mass: 308.099 g/mol

(573) HPLC-MS: analytical method A

(574) rt: 1.937 min-found mass: 309 (m/z+H)

Example #118

Preparation of N-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(575) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 6-(4-methylpiperazin-1-yl)pyridin-3-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(576) exact mass: 392.1821 g/mol

(577) HPLC-MS: analytical method C

(578) rt: 1.428 min-found mass: 393 (m/z+H)

Example #119

Preparation of N-(4-(4-ethylpiperazin-1-yl)phenyl)-5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(579) 7-chloro-2-(4-methoxybenzyl)-5-phenyl-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-ethylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(580) exact mass: 399.2561 g/mol

(581) HPLC-MS: analytical method C

(582) rt: 1.586 min-found mass: 400 (m/z+H)

Example #120

Preparation of N-(4-((dimethylamino)methyl)phenyl)-5-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(583) 7-chloro-2-(4-methoxybenzyl)-5-phenyl-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-((dimethylamino)methyl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(584) exact mass: 344.2051 g/mol

(585) HPLC-MS: analytical method C

(586) rt: 1.601 min-found mass: 345 (m/z+H)

Example #121

Preparation of 5-(2,5-dimethoxyphenyl)-N-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(587) 7-chloro-5-(2,5-dimethoxyphenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(588) exact mass: 407.1896 g/mol

(589) HPLC-MS: analytical method A

(590) rt: 2.363 min-found mass: 408 (m/z+H)

Example #122

Preparation of 5-(2,5-dimethoxyphenyl)-N-(4-(4-ethylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(591) 7-chloro-5-(2,5-dimethoxyphenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-ethylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(592) exact mass: 459.2839 g/mol

(593) HPLC-MS: analytical method A

(594) rt: 1.848 min-found mass: 460 (m/z+H)

Example #123

Preparation of N-(4-(4-cyclopropylpiperazin-1-yl)phenyl)-5-(2,5-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(595) 7-chloro-5-(2,5-dimethoxyphenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-cyclopropylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(596) exact mass: 471.2833 g/mol

(597) HPLC-MS: analytical method A

(598) rt: 1.976 min-found mass: 472 (m/z+H)

Example #124

Preparation of N-(3,4-dimethoxyphenyl)-5-(imidazo[1,2-a]pyridin-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(599) 7-chloro-5-(imidazo[1,2-a]pyridin-2-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(600) exact mass: 387.1664 g/mol

(601) HPLC-MS: analytical method A

(602) rt: 1.962 min-found mass: 388 (m/z+H)

Example #125

Preparation of N-(4-(4-ethylpiperazin-1-yl)phenyl)-5-(imidazo[1,2-a]pyridin-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(603) 7-chloro-5-(imidazo[1,2-a]pyridin-2-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-ethylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(604) exact mass: 439.2607 g/mol

(605) HPLC-MS: analytical method C

(606) rt: 1.787 min-found mass: 440 (m/z+H)

Example #126

Preparation of 5-(imidazo[1,2-a]pyridin-2-yl)-N-(1H-indazol-5-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(607) 7-chloro-5-(imidazo[1,2-a]pyridin-2-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1H-indazol-5-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(608) exact mass: 367.1431 g/mol

(609) HPLC-MS: analytical method A

(610) rt: 1.835 min-found mass: 368 (m/z+H)

Example #127

Preparation of 5-(imidazo[1,2-a]pyridin-2-yl)-N-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(611) 7-chloro-5-(imidazo[1,2-a]pyridin-2-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1H-indazol-6-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(612) exact mass: 367.1431 g/mol

(613) HPLC-MS: analytical method A

(614) rt: 1.900 min-found mass: 368 (m/z+H)

Example #128

Preparation of 4-((5-(imidazo[1,2-a]pyridin-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)benzoic-acid

(615) 7-chloro-5-(imidazo[1,2-a]pyridin-2-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-aminobenzoic-acid (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(616) exact mass: 371.1269 g/mol

(617) HPLC-MS: analytical method C

(618) rt: 2.104 min-found mass: 372 (m/z+H)

Example #129

Preparation of 5-(1H-benzo[d]imidazol-2-yl)-N-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(619) 5-(1H-benzo[d]imidazol-2-yl)-7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(620) exact mass: 387.1664 g/mol

(621) HPLC-MS: analytical method A

(622) rt: 2.255 min-found mass: 388 (m/z+H)

Example #130

Preparation of N-(3,4-dimethoxyphenyl)-5-(1-methyl-1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(623) 7-chloro-2-(4-methoxybenzyl)-5-(1-methyl-1H-benzo[d]imidazol-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(624) exact mass: 401.1859 g/mol

(625) HPLC-MS: analytical method A

(626) rt: 2.267 min-found mass: 402 (m/z+H)

Example #131

Preparation of 5-(3-methoxyphenyl)-N-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(627) 7-chloro-2-(4-methoxybenzyl)-5-(3-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-Amino-phenyl)-(4-methyl-piperazin-1-yl)-methanone (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and dissolved in THF (dry) LiAlH4 powder was added (excess, 2 by 2 eq) until completion of reaction is observed (by LCMS). The reaction was quenched with water (1 mL per gram LiAlH4), then NaOH (ca. 15% aq., 1 mL per g LiAlH4), water (3 mL per gram LiAlH4). The mixture was filtered, washed with THF, MeOH, MeCN (ca. 10 mL each). The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(628) exact mass: 429.27 g/mol

(629) HPLC-MS: analytical method A

(630) rt: 2.239 min-found mass: 430 (m/z+H)

Example #132

Preparation of 5-(3-methoxyphenyl)-N-(4-(pyrrolidin-1-ylmethyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(631) 7-chloro-2-(4-methoxybenzyl)-5-(3-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and (4-Amino-phenyl)-pyrrolidin-1-yl-methanone (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and dissolved in THF (dry) LiAlH4 powder was added (excess, 2 by 2 eq) until completion of reaction is observed (by LCMS). The reaction was quenched with water (1 mL per gram LiAlH4), then NaOH (ca. 15% aq., 1 mL per g LiAlH4), water (3 mL per gram LiAlH4). The mixture was filtered, washed with THF, MeOH, MeCN (ca. 10 mL each). The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(632) exact mass: 400.238 g/mol

(633) HPLC-MS: analytical method A

(634) rt: 2.021 min-found mass: 401 (m/z+H)

Example #133

Preparation of 1-(4-((5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)-3-(m-tolyl)urea

(635) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1-(4-aminophenyl)-3-(m-tolyl)urea (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(636) exact mass: 441.1620 g/mol

(637) HPLC-MS: analytical method C

(638) rt: 2.74 min-found mass: 442 (m/z+H)

Example #134

Preparation of (4-methylpiperazin-1-yl)(4-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)methanone

(639) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and (4-aminophenyl)(4-methylpiperazin-1-yl)methanone (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(640) exact mass: 419.1830 g/mol

(641) HPLC-MS: analytical method C

(642) rt: 1.97 min-found mass: 420 (m/z+H)

Example #135

Preparation of pyrrolidin-1-yl(4-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)methanone

(643) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and (4-aminophenyl)(pyrrolidin-1-yl)methanone (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(644) exact mass: 390.1510 g/mol

(645) HPLC-MS: analytical method J

(646) rt: 5.14 min-found mass: 391 (m/z+H)

Example #136

Preparation of N-(4-thiomorpholinophenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(647) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-thiomorpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(648) exact mass: 394.1286 g/mol

(649) HPLC-MS: analytical method C

(650) rt: 2.81 min-found mass: 395 (m/z+H)

Example #137

Preparation of 4-(4-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)thiomorpholine 1,1-dioxide

(651) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-aminophenyl)thiomorpholine 1,1-dioxide (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(652) exact mass: 426.1174 g/mol

(653) HPLC-MS: analytical method A

(654) rt: 2.32 min-found mass: 427 (m/z+H)

Example #138

Preparation of 1-(4-(4-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one

(655) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1-(4-(4-aminophenyl)piperazin-1-yl)ethan-1-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(656) exact mass: 419.1830 g/mol

(657) HPLC-MS: analytical method J

(658) rt: 4.21 min-found mass: 420 (m/z+H)

Example #139

Preparation of (3-methoxy-4-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)(4-(4-methylpiperazin-1-yl)piperidin-1-yl)methanone

(659) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and (4-amino-3-methoxyphenyl)(4-(4-methylpiperazin-1-yl)piperidin-1-yl)methanone (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(660) exact mass: 532.2869 g/mol

(661) HPLC-MS: analytical method A

(662) rt: 1.91 min-found mass: 533 (m/z+H)

Example #140

Preparation of 5-(1H-imidazol-5-yl)-N-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(663) 7-chloro-5-(1H-imidazol-5-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(664) exact mass: 375.2231 g/mol

(665) HPLC-MS: analytical method A

(666) rt: 0.47 min-found mass: 376 (m/z+H)

Example #141

Preparation of 5-(1H-imidazol-2-yl)-N-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(667) 7-chloro-5-(1H-imidazol-2-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(668) exact mass: 375.2231 g/mol

(669) HPLC-MS: analytical method A

(670) rt: 0.41 min-found mass: 376 (m/z+H)

Example #142

Preparation of pyrrolidin-1-yl(4-((5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)methanone

(671) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and (4-aminophenyl)(pyrrolidin-1-yl)methanone (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(672) exact mass: 390.1510 g/mol

(673) HPLC-MS: analytical method A

(674) rt: 2.40 min-found mass: 391 (m/z+H)

Example #143

Preparation of 4-(4-((5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)thiomorpholine 1,1-dioxide

(675) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-aminophenyl)thiomorpholine 1,1-dioxide (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(676) exact mass: 426.1174 g/mol

(677) HPLC-MS: analytical method A

(678) rt: 2.14 min-found mass: 427 (m/z+H)

Example #144

Preparation of 1-(4-(4-((5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one

(679) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1-(4-(4-aminophenyl)piperazin-1-yl)ethan-1-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(680) exact mass: 419.1830 g/mol

(681) HPLC-MS: analytical method A

(682) rt: 2.11 min-found mass: 420 (m/z+H)

Example #145

Preparation of N-(4-thiomorpholinophenyl)-5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(683) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-thiomorpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(684) exact mass: 394.1286 g/mol

(685) HPLC-MS: analytical method A

(686) rt: 2.50 min-found mass: 395 (m/z+H)

Example #146

Preparation of 6-((5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2H-benzo[b][1,4]oxazin-3(4H)-one

(687) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 6-amino-2H-benzo[b][1,4]oxazin-3(4H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(688) exact mass: 364.0869 g/mol

(689) HPLC-MS: analytical method A

(690) rt: 2.17 min-found mass: 365 (m/z+H)

Example #147

Preparation of (4-methylpiperazin-1-yl)(4-((5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)methanone

(691) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and (4-aminophenyl)(4-methylpiperazin-1-yl)methanone (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(692) exact mass: 419.1830 g/mol

(693) HPLC-MS: analytical method A

(694) rt: 0.29 min-found mass: 420 (m/z+H)

Example #148

Preparation of 2,2-dimethyl-N-(5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-3,4-dihydro-2H-benzo[b][1,4]thiazin-6-amine

(695) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 2,2-dimethyl-3,4-dihydro-2H-benzo[b][1,4]thiazin-6-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(696) exact mass: 394.1286 g/mol

(697) HPLC-MS: analytical method C

(698) rt: 2.95 min-found mass: 395 (m/z+H)

Example #149

Preparation of 5-(3-(2H-tetrazol-5-yl)phenyl)-N-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(699) 5-(3-(2H-tetrazol-5-yl)phenyl)-7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(700) exact mass: 453.2462 g/mol

(701) HPLC-MS: analytical method L

(702) rt: 3.29 min-found mass: 454 (m/z+H)

Example #150

Preparation of (7-((2-(dimethylamino)ethyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)(phenyl)methanone

(703) (7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)(phenyl)methanone (0.16 mmol) and N1,N1-dimethylethane-1,2-diamine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(704) exact mass: 310.1815 g/mol

(705) HPLC-MS: analytical method L

(706) rt: 3.17 min-found mass: 311 (m/z+H)

Example #151

Preparation of (7-(((1-methylpiperidin-4-yl)methyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)(phenyl)methanone

(707) (7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)(phenyl)methanone (0.16 mmol) and (1-methylpiperidin-4-yl)methanamine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(708) exact mass: 350.2200 g/mol

(709) HPLC-MS: analytical method L

(710) rt: 2.92 min-found mass: 351 (m/z+H)

Example #152

Preparation of (7-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)(phenyl)methanone

(711) (7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)(phenyl)methanone (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(712) exact mass: 413.2305 g/mol

(713) HPLC-MS: analytical method L

(714) rt: 3.50 min-found mass: 414 (m/z+H)

Example #153

Preparation of (7-((3,4-dimethoxyphenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)(phenyl)methanone

(715) (7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)(phenyl)methanone (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(716) exact mass: 375.1558 g/mol

(717) HPLC-MS: analytical method L

(718) rt: 4.51 min-found mass: 376 (m/z+H)

Example #154

Preparation of (4-((5-benzoyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)(pyrrolidin-1-yl)methanone

(719) (7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)(phenyl)methanone (0.16 mmol) and (4-aminophenyl)(pyrrolidin-1-yl)methanone (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(720) exact mass: 412.1924 g/mol

(721) HPLC-MS: analytical method L

(722) rt: 4.42 min-found mass: 413 (m/z+H)

Example #155

Preparation of 7-((5-benzoyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3,4-dihydroquinolin-2(1H)-one

(723) (7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)(phenyl)methanone (0.16 mmol) and 7-amino-3,4-dihydroquinolin-2(1H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(724) exact mass: 384.1534 g/mol

(725) HPLC-MS: analytical method L

(726) rt: 4.22 min-found mass: 385 (m/z+H)

Example #156

Preparation of 3-(7-((4-morpholinophenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoic acid

(727) Methyl 3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate (0.16 mmol) and 4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. For the saponification the residue was dissolved in methanol. 2M aqueous NaOH-solution was added to ensure basic conditions. The mixture was irradiated in a microwave reactor for 10 min at 120° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(728) exact mass: 416.1872 g/mol

(729) HPLC-MS: analytical method A

(730) rt: 2.39 min-found mass: 417 (m/z+H)

Example #157

Preparation of morpholino(4-((5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)methanone

(731) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and (4-aminophenyl)(morpholino)methanone (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(732) exact mass: 406.1454 g/mol

(733) HPLC-MS: analytical method A

(734) rt: 2.44 min-found mass: 407 (m/z+H)

Example #158

Preparation of 6-((5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2H-benzo[b][1,4]thiazin-3(4H)-one

(735) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 6-amino-2H-benzo[b][1,4]thiazin-3(4H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(736) exact mass: 380.0640 g/mol

(737) HPLC-MS: analytical method A

(738) rt: 2.58 min-found mass: 381 (m/z+H)

Example #159

Preparation of 7-((5-(4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3,4-dihydroquinolin-2(1H)-one

(739) 7-chloro-2-(4-methoxybenzyl)-5-(4-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 7-amino-3,4-dihydroquinolin-2(1H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(740) exact mass: 386.1733 g/mol

(741) HPLC-MS: analytical method A

(742) rt: 2.30 min-found mass: 387 (m/z+H)

Example #160

Preparation of (4-((5-(4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)(pyrrolidin-1-yl)methanone

(743) 7-chloro-2-(4-methoxybenzyl)-5-(4-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and (4-aminophenyl)(pyrrolidin-1-yl)methanone (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(744) exact mass: 414.2123 g/mol

(745) HPLC-MS: analytical method A

(746) rt: 2.44 min-found mass: 415 (m/z+H)

Example #161

Preparation of N-(4-(4-(tert-butyl)piperazin-1-yl)phenyl)-5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(747) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-(tert-butyl)piperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(748) exact mass: 433.2476 g/mol

(749) HPLC-MS: analytical method L

(750) rt: 3.23 min-found mass: 434 (m/z+H)

Example #162

Preparation of 6-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2H-benzo[b][1,4]oxazin-3(4H)-one

(751) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 6-amino-2H-benzo[b][1,4]oxazin-3(4H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(752) exact mass: 364.0869 g/mol

(753) HPLC-MS: analytical method A

(754) rt: 2.40 min-found mass: 365 (m/z+H)

Example #163

Preparation of N-(4-(4-(tert-butyl)piperazin-1-yl)phenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(755) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-(tert-butyl)piperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(756) exact mass: 433.2476 g/mol

(757) HPLC-MS: analytical method A

(758) rt: 1.94 min-found mass: 434 (m/z+H)

Example #164

Preparation of 8-((5-(4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-4,5-dihydro-1H-benzo[b]azepin-2(3H)-one

(759) 7-chloro-2-(4-methoxybenzyl)-5-(4-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 8-amino-4,5-dihydro-1H-benzo[b]azepin-2(3H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(760) exact mass: 400.1928 g/mol

(761) HPLC-MS: analytical method A

(762) rt: 2.33 min-found mass: 401 (m/z+H)

Example #165

Preparation of 6-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2H-benzo[b][1,4]thiazin-3(4H)-one

(763) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 6-amino-2H-benzo[b][1,4]thiazin-3(4H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(764) exact mass: 380.0640 g/mol

(765) HPLC-MS: analytical method A

(766) rt: 2.63 min-found mass: 381 (m/z+H)

Example #166

Preparation of 1-methyl-N-(5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-1,2,3,4-tetrahydroquinolin-7-amine

(767) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1-methyl-1,2,3,4-tetrahydroquinolin-7-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(768) exact mass: 362.1571 g/mol

(769) HPLC-MS: analytical method L

(770) rt: 4.78 min-found mass: 363 (m/z+H)

Example #167

Preparation of 2-methyl-2-(4-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)propanenitrile

(771) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 2-(4-aminophenyl)-2-methylpropanenitrile (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(772) exact mass: 360.1371 g/mol

(773) HPLC-MS: analytical method A

(774) rt: 3.12 min-found mass: 361 (m/z+H)

Example #168

Preparation of 5-(4-methoxyphenyl)-N-(4-thiomorpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(775) 7-chloro-2-(4-methoxybenzyl)-5-(4-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-thiomorpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(776) exact mass: 418.1899 g/mol

(777) HPLC-MS: analytical method A

(778) rt: 2.57 min-found mass: 419 (m/z+H)

Example #169

Preparation of 4-(4-((5-(4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)thiomorpholine 1,1-dioxide

(779) 7-chloro-2-(4-methoxybenzyl)-5-(4-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-aminophenyl)thiomorpholine 1,1-dioxide (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(780) exact mass: 450.1787 g/mol

(781) HPLC-MS: analytical method A

(782) rt: 2.23 min-found mass: 451 (m/z+H)

Example #170

Preparation of 1-(4-(4-((5-(4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one

(783) 7-chloro-2-(4-methoxybenzyl)-5-(4-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1-(4-(4-aminophenyl)piperazin-1-yl)ethan-1-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(784) exact mass: 443.2443 g/mol

(785) HPLC-MS: analytical method A

(786) rt: 2.21 min-found mass: 444 (m/z+H)

Example #171

Preparation of 6-((5-(4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-2H-benzo[b][1,4]oxazin-3(4H)-one

(787) 7-chloro-2-(4-methoxybenzyl)-5-(4-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 6-amino-2H-benzo[b][1,4]oxazin-3(4H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(788) exact mass: 388.1483 g/mol

(789) HPLC-MS: analytical method A

(790) rt: 2.26 min-found mass: 389 (m/z+H)

Example #172

Preparation of N-(4-(4-(tert-butyl)piperazin-1-yl)phenyl)-5-(4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(791) 7-chloro-2-(4-methoxybenzyl)-5-(4-methoxyphenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-(tert-butyl)piperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(792) exact mass: 457.3090 g/mol

(793) HPLC-MS: analytical method C

(794) rt: 2.13 min-found mass: 458 (m/z+H)

Example #173

Preparation of 2,2-dimethyl-N-(5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-3,4-dihydro-2H-benzo[b][1,4]thiazin-6-amine

(795) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 2,2-dimethyl-3,4-dihydro-2H-benzo[b][1,4]thiazin-6-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(796) exact mass: 394.1286 g/mol

(797) HPLC-MS: analytical method A

(798) rt: 3.18 min-found mass: 395 (m/z+H)

Example #174

Preparation of 2-(3-(7-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenoxy)acetic acid

(799) 2-(3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)phenoxy)acetic acid methyl ester (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. For the saponification the residue was dissolved in methanol. 2M aqueous NaOH-solution was added to ensure basic conditions. The mixture was irradiated in a microwave reactor for 10 min at 120° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(800) exact mass: 459.2388 g/mol

(801) HPLC-MS: analytical method L

(802) rt: 3.04 min-found mass: 460 (m/z+H)

Example #175

Preparation of 5-(7-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)thiophene-3-carboxylic acid

(803) 5-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)thiophene-3-carboxylic acid methyl ester (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. For the saponification the residue was dissolved in methanol. 2M aqueous NaOH-solution was added to ensure basic conditions. The mixture was irradiated in a microwave reactor for 10 min at 120° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(804) exact mass: 435.1774 g/mol

(805) HPLC-MS: analytical method L

(806) rt: 3.19 min-found mass: 436 (m/z+H)

Example #176

Preparation of 2-(3-(7-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)acetic acid

(807) 2-(3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)acetic acid methyl ester (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. For the saponification the residue was dissolved in methanol. 2M aqueous NaOH-solution was added to ensure basic conditions. The mixture was irradiated in a microwave reactor for 10 min at 120° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(808) exact mass: 443.2444 g/mol

(809) HPLC-MS: analytical method L

(810) rt: 3.06 min-found mass: 444 (m/z+H)

Example #177

Preparation of 6-(7-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)picolinic acid

(811) 6-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)picolinic acid methyl ester (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. For the saponification the residue was dissolved in methanol. 2M aqueous NaOH-solution was added to ensure basic conditions. The mixture was irradiated in a microwave reactor for 10 min at 120° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(812) exact mass: 430.2179 g/mol

(813) HPLC-MS: analytical method L

(814) rt: 2.70 min-found mass: 431 (m/z+H)

Example #178

Preparation of N-(4-(pentafluorosulfanyl)phenyl)-5-(thiophen-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(815) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-3-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-Aminophenylsulphur pentafluoride (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(816) exact mass: 419.0376 g/mol

(817) HPLC-MS: analytical method C

(818) rt: 3.40 min-found mass: 420 (m/z+H)

Example #179

Preparation of N-(4-(4-methylpiperazin-1-yl)phenyl)-5-(thiazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(819) 2-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)thiazole (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(820) exact mass: 392.1821 g/mol

(821) HPLC-MS: analytical method D

(822) rt: 2.67 min-found mass: 393 (m/z+H)

Example #180

Preparation of 5-(3-(((4-methylbenzyl)amino)methyl)phenyl)-N-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(823) N-(3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzyl)-1-(p-tolyl)methanamine (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(824) exact mass: 518.3447 g/mol

(825) HPLC-MS: analytical method L

(826) rt: 3.20 min-found mass: 519 (m/z+H)

Example #181

Preparation of 5-(3-(3-(dimethylamino)propoxy)phenyl)-N-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(827) 3-(3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)phenoxy)-N,N-dimethylpropan-1-amine (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(828) exact mass: 486.3410 g/mol

(829) HPLC-MS: analytical method L

(830) rt: 3.21 min-found mass: 487 (m/z+H)

Example #182

Preparation of 3-(7-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide

(831) 3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(832) exact mass: 464.2094 g/mol

(833) HPLC-MS: analytical method L

(834) rt: 0.46 min-found mass: 465 (m/z+H)

Example #183

Preparation of 3-(7-((3,4-dimethoxyphenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide

(835) 3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(836) exact mass: 426.1346 g/mol

(837) HPLC-MS: analytical method L

(838) rt: 3.91 min-found mass: 427 (m/z+H)

Example #184

Preparation of 1-(4-(4-((5-(thiazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one

(839) 2-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)thiazole (0.16 mmol) and 1-(4-(4-aminophenyl)piperazin-1-yl)ethan-1-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(840) exact mass: 420.1760 g/mol

(841) HPLC-MS: analytical method L

(842) rt: 3.66 min-found mass: 421 (m/z+H)

Example #185

Preparation of N-(3,4-dimethoxyphenyl)-5-(thiazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(843) 2-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)thiazole (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(844) exact mass: 354.1073 g/mol

(845) HPLC-MS: analytical method L

(846) rt: 3.93 min-found mass: 355 (m/z+H)

Example #186

Preparation of 7-((5-(thiazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3,4-dihydroquinolin-2(1H)-one

(847) 2-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)thiazole (0.16 mmol) and 7-amino-3,4-dihydroquinolin-2(1H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(848) exact mass: 363.1049 g/mol

(849) HPLC-MS: analytical method A

(850) rt: 2.30 min-found mass: 364 (m/z+H)

Example #187

Preparation of N-(3-(7-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide

(851) N-(3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(852) exact mass: 478.2289 g/mol

(853) HPLC-MS: analytical method D

(854) rt: 3.27 min-found mass: 479 (m/z+H)

Example #188

Preparation of N-(3-(7-((4-(piperazin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide

(855) N-(3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide (0.16 mmol) and 4-(piperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(856) exact mass: 464.2094 g/mol

(857) HPLC-MS: analytical method L

(858) rt: 2.90 min-found mass: 465 (m/z+H)

Example #189

Preparation of N-(3-(7-((3,4-dimethoxyphenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide

(859) N-(3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(860) exact mass: 440.1541 g/mol

(861) HPLC-MS: analytical method L

(862) rt: 4.06 min-found mass: 441 (m/z+H)

Example #190

Preparation of N-(3-(7-((2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide

(863) N-(3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide (0.16 mmol) and 7-amino-3,4-dihydroquinolin-2(1H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(864) exact mass: 449.1518 g/mol

(865) HPLC-MS: analytical method D

(866) rt: 4.65 min-found mass: 450 (m/z+H)

Example #191

Preparation of N-(3-(7-((4-(4-acetylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide

(867) N-(3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide (0.16 mmol) and 1-(4-(4-aminophenyl)piperazin-1-yl)ethan-1-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(868) exact mass: 506.2228 g/mol

(869) HPLC-MS: analytical method L

(870) rt: 3.75 min-found mass: 507 (m/z+H)

Example #192

Preparation of 1-(4-(4-((5-(3-(2H-tetrazol-5-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one

(871) 5-(3-(2H-tetrazol-5-yl)phenyl)-7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1-(4-(4-aminophenyl)piperazin-1-yl)ethan-1-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(872) exact mass: 481.2401 g/mol

(873) HPLC-MS: analytical method A

(874) rt: 2.34 min-found mass: 482 (m/z+H)

Example #193

Preparation of 5-(3-(2H-tetrazol-5-yl)phenyl)-N-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(875) 5-(3-(2H-tetrazol-5-yl)phenyl)-7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(876) exact mass: 415.1714 g/mol

(877) HPLC-MS: analytical method A

(878) rt: 2.49 min-found mass: 416 (m/z+H)

Example #194

Preparation of 3-(7-((3,4-dimethoxyphenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoic acid

(879) 3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoic acid methyl ester (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. For the saponification the residue was dissolved in methanol. 2M aqueous NaOH-solution was added to ensure basic conditions. The mixture was irradiated in a microwave reactor for 10 min at 120° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(880) exact mass: 391.1501 g/mol

(881) HPLC-MS: analytical method L

(882) rt: 4.04 min-found mass: 392 (m/z+H)

Example #195

Preparation of 3-(7-((2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoic acid

(883) 3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoic acid methyl ester (0.16 mmol) and 7-amino-3,4-dihydroquinolin-2(1H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. For the saponification the residue was dissolved in methanol. 2M aqueous NaOH-solution was added to ensure basic conditions. The mixture was irradiated in a microwave reactor for 10 min at 120° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(884) exact mass: 400.1478 g/mol

(885) HPLC-MS: analytical method L

(886) rt: 4.02 min-found mass: 401 (m/z+H)

Example #196

Preparation of 7-((5-(3-(2H-tetrazol-5-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3,4-dihydroquinolin-2(1H)-one

(887) 5-(3-(2H-tetrazol-5-yl)phenyl)-7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 7-amino-3,4-dihydroquinolin-2(1H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(888) exact mass: 424.1690 g/mol

(889) HPLC-MS: analytical method L

(890) rt: 3.97 min-found mass: 425 (m/z+H)

Example #197

Preparation of N-(4-(4-methylpiperazin-1-yl)phenyl)-5-(thiazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(891) 4-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)thiazole (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(892) exact mass: 392.1821 g/mol

(893) HPLC-MS: analytical method CP

(894) rt: 2.13 min-found mass: 393 (m/z+H)

Example #198

Preparation of 1-(4-(4-((5-(thiazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one

(895) 4-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)thiazole (0.16 mmol) and 1-(4-(4-aminophenyl)piperazin-1-yl)ethan-1-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(896) exact mass: 420.1760 g/mol

(897) HPLC-MS: analytical method L

(898) rt: 3.32 min-found mass: 421 (m/z+H)

Example #199

Preparation of N-(3,4-dimethoxyphenyl)-5-(thiazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(899) 4-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)thiazole (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(900) exact mass: 354.1073 g/mol

(901) HPLC-MS: analytical method L

(902) rt: 3.47 min-found mass: 355 (m/z+H)

Example #200

Preparation of N-(4-(4-methylpiperazin-1-yl)phenyl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(903) 4-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)oxazole (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(904) exact mass: 376.2050 g/mol

(905) HPLC-MS: analytical method CP

(906) rt: 2.18 min-found mass: 377 (m/z+H)

Example #201

Preparation of 1-(4-(4-((5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one

(907) 4-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)oxazole (0.16 mmol) and 1-(4-(4-aminophenyl)piperazin-1-yl)ethan-1-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(908) exact mass: 404.1989 g/mol

(909) HPLC-MS: analytical method A

(910) rt: 2.01 min-found mass: 405 (m/z+H)

Example #202

Preparation of N-(3,4-dimethoxyphenyl)-5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(911) 4-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)oxazole (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(912) exact mass: 338.1302 g/mol

(913) HPLC-MS: analytical method A

(914) rt: 2.13 min-found mass: 339 (m/z+H)

Example #203

Preparation of N-(4-(4-methylpiperazin-1-yl)phenyl)-5-(oxazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(915) 2-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)oxazole (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(916) exact mass: 376.2050 g/mol

(917) HPLC-MS: analytical method CP

(918) rt: 2.23 min-found mass: 377 (m/z+H)

Example #204

Preparation of 1-(4-(4-((5-(oxazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one

(919) 2-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)oxazole (0.16 mmol) and 1-(4-(4-aminophenyl)piperazin-1-yl)ethan-1-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(920) exact mass: 404.1989 g/mol

(921) HPLC-MS: analytical method L

(922) rt: 3.59 min-found mass: 405 (m/z+H)

Example #205

Preparation of N-(3,4-dimethoxyphenyl)-5-(oxazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(923) 2-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)oxazole (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(924) exact mass: 338.1302 g/mol

(925) HPLC-MS: analytical method L

(926) rt: 3.88 min-found mass: 339 (m/z+H)

Example #206

Preparation of 7-((5-(thiazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3,4-dihydroquinolin-2(1H)-one

(927) 4-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)thiazole (0.16 mmol) and 7-amino-3,4-dihydroquinolin-2(1H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(928) exact mass: 363.1049 g/mol

(929) HPLC-MS: analytical method L

(930) rt: 3.42 min-found mass: 364 (m/z+H)

Example #207

Preparation of 7-((5-(oxazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3,4-dihydroquinolin-2(1H)-one

(931) 4-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)oxazole (0.16 mmol) and 7-amino-3,4-dihydroquinolin-2(1H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(932) exact mass: 347.1278 g/mol

(933) HPLC-MS: analytical method L

(934) rt: 3.47 min-found mass: 348 (m/z+H)

Example #208

Preparation of 7-((5-(oxazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3,4-dihydroquinolin-2(1H)-one

(935) 2-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)oxazole (0.16 mmol) and 7-amino-3,4-dihydroquinolin-2(1H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(936) exact mass: 347.1278 g/mol

(937) HPLC-MS: analytical method L

(938) rt: 3.68 min-found mass: 348 (m/z+H)

Example #209

Preparation of N-(4-(1-methylpiperidin-4-yl)phenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(939) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(1-methylpiperidin-4-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(940) exact mass: 390.1961 g/mol

(941) HPLC-MS: analytical method L

(942) rt: 4.22 min-found mass: 391 (m/z+H)

Example #210

Preparation of methyl 3-(7-((2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate

(943) methyl 3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate (0.16 mmol) and 7-amino-3,4-dihydroquinolin-2(1H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(944) exact mass: 414.1673 g/mol

(945) HPLC-MS: analytical method L

(946) rt: 4.53 min-found mass: 415 (m/z+H)

Example #211

Preparation of methyl 3-(7-((3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate

(947) methyl 3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate (0.16 mmol) and 6-amino-2H-benzo[b][1,4]oxazin-3(4H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(948) exact mass: 416.1422 g/mol

(949) HPLC-MS: analytical method L

(950) rt: 4.50 min-found mass: 417 (m/z+H)

Example #212

Preparation of 3-(7-((3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoic acid

(951) 3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoic acid methyl ester (0.16 mmol) and 6-amino-2H-benzo[b][1,4]oxazin-3(4H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. For the saponification the residue was dissolved in methanol. 2M aqueous NaOH-solution was added to ensure basic conditions. The mixture was irradiated in a microwave reactor for 10 min at 120° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(952) exact mass: 402.1227 g/mol

(953) HPLC-MS: analytical method D

(954) rt: 4.69 min-found mass: 403 (m/z+H)

Example #213

Preparation of methyl 4-(7-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate

(955) methyl 4-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(956) exact mass: 443.2443 g/mol

(957) HPLC-MS: analytical method L

(958) rt: 3.54 min-found mass: 444 (m/z+H)

Example #214

Preparation of methyl 4-(7-((3,4-dimethoxyphenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate

(959) methyl 4-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(960) exact mass: 405.1697 g/mol

(961) HPLC-MS: analytical method L

(962) rt: 4.81 min-found mass: 406 (m/z+H)

Example #215

Preparation of methyl 4-(7-((2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate

(963) methyl 4-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate (0.16 mmol) and 7-amino-3,4-dihydroquinolin-2(1H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(964) exact mass: 414.1673 g/mol

(965) HPLC-MS: analytical method L

(966) rt: 4.54 min-found mass: 415 (m/z+H)

Example #216

Preparation of methyl 3-(7-((3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazin-6-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate

(967) methyl 3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate (0.16 mmol) and 6-amino-2H-benzo[b][1,4]thiazin-3(4H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(968) exact mass: 432.1193 g/mol

(969) HPLC-MS: analytical method L

(970) rt: 4.81 min-found mass: 433 (m/z+H)

Example #217

Preparation of methyl 3-(7-((2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-8-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate

(971) methyl 3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate (0.16 mmol) and 8-amino-4,5-dihydro-1H-benzo[b]azepin-2(3H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(972) exact mass: 428.1868 g/mol

(973) HPLC-MS: analytical method L

(974) rt: 4.65 min-found mass: 429 (m/z+H)

Example #218

Preparation of 3-(7-((2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-8-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoic acid

(975) 3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoic acid methyl ester (0.16 mmol) and 8-amino-4,5-dihydro-1H-benzo[b]azepin-2(3H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. For the saponification the residue was dissolved in methanol. 2M aqueous NaOH-solution was added to ensure basic conditions. The mixture was irradiated in a microwave reactor for 10 min at 120° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(976) exact mass: 414.1673 g/mol

(977) HPLC-MS: analytical method L

(978) rt: 4.04 min-found mass: 415 (m/z+H)

Example #219

Preparation of N-(3,4-dimethoxyphenyl)-5-(3-(pentafluorosulfanyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(979) 7-chloro-5-(3-(pentafluorosulfanyl)phenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(980) exact mass: 473.1128 g/mol

(981) HPLC-MS: analytical method D

(982) rt: 7.77 min-found mass: 474 (m/z+H)

Example #220

Preparation of 5-(3-(pentafluorosulfanyl)phenyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(983) 7-chloro-5-(3-(pentafluorosulfanyl)phenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(984) exact mass: 498.1500 g/mol

(985) HPLC-MS: analytical method D

(986) rt: 7.74 min-found mass: 499 (m/z+H)

Example #221

Preparation of N-(4-(4-methylpiperazin-1-yl)phenyl)-5-(3-(pentafluorosulfanyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(987) 7-chloro-5-(3-(pentafluorosulfanyl)phenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(988) exact mass: 511.1876 g/mol

(989) HPLC-MS: analytical method D

(990) rt: 5.24 min-found mass: 512 (m/z+H)

Example #222

Preparation of 7-((5-(3-(pentafluorosulfanyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3,4-dihydroquinolin-2(1H)-one

(991) 7-chloro-5-(3-(pentafluorosulfanyl)phenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 7-amino-3,4-dihydroquinolin-2(1H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(992) exact mass: 482.1105 g/mol

(993) HPLC-MS: analytical method D

(994) rt: 7.25 min-found mass: 483 (m/z+H)

Example #223

Preparation of N-(3,4-dimethoxyphenyl)-5-(3-(methylthio)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(995) 7-chloro-2-(4-methoxybenzyl)-5-(3-(methylthio)phenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(996) exact mass: 393.1528 g/mol

(997) HPLC-MS: analytical method D

(998) rt: 6.18 min-found mass: 394 (m/z+H)

Example #224

Preparation of 5-(3-(methylthio)phenyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(999) 7-chloro-2-(4-methoxybenzyl)-5-(3-(methylthio)phenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1000) exact mass: 418.1899 g/mol

(1001) HPLC-MS: analytical method D

(1002) rt: 6.11 min-found mass: 419 (m/z+H)

Example #225

Preparation of N-(4-(4-methylpiperazin-1-yl)phenyl)-5-(3-(methylthio)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1003) 7-chloro-2-(4-methoxybenzyl)-5-(3-(methylthio)phenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1004) exact mass: 431.2275 g/mol

(1005) HPLC-MS: analytical method D

(1006) rt: 3.80 min-found mass: 432 (m/z+H)

Example #226

Preparation of N-(3,4-dimethoxyphenyl)-5-(3-(trifluoromethoxy)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1007) 7-chloro-2-(4-methoxybenzyl)-5-(3-(trifluoromethoxy)phenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1008) exact mass: 431.1394 g/mol

(1009) HPLC-MS: analytical method A

(1010) rt: 3.35 min-found mass: 432 (m/z+H)

Example #227

Preparation of N-(4-morpholinophenyl)-5-(3-(trifluoromethoxy)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1011) 7-chloro-2-(4-methoxybenzyl)-5-(3-(trifluoromethoxy)phenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1012) exact mass: 456.1765 g/mol

(1013) HPLC-MS: analytical method A

(1014) rt: 3.31 min-found mass: 457 (m/z+H)

Example #228

Preparation of N-(3,4-dimethoxyphenyl)-5-(3-(trifluoromethyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1015) 7-chloro-2-(4-methoxybenzyl)-5-(3-(trifluoromethyl)phenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1016) exact mass: 415.1450 g/mol

(1017) HPLC-MS: analytical method A

(1018) rt: 3.30 min-found mass: 416 (m/z+H)

Example #229

Preparation of N-(4-morpholinophenyl)-5-(3-(trifluoromethyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1019) 7-chloro-2-(4-methoxybenzyl)-5-(3-(trifluoromethyl)phenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1020) exact mass: 440.1821 g/mol

(1021) HPLC-MS: analytical method A

(1022) rt: 3.28 min-found mass: 441 (m/z+H)

Example #230

Preparation of 5-(3-chlorophenyl)-N-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1023) 7-chloro-5-(3-chlorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1024) exact mass: 381.1201 g/mol

(1025) HPLC-MS: analytical method A

(1026) rt: 3.23 min-found mass: 382 (m/z+H)

Example #231

Preparation of 5-(3-chlorophenyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1027) 7-chloro-5-(3-chlorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1028) exact mass: 406.1572 g mol

(1029) HPLC-MS: analytical method A

(1030) rt: 3.20 min-found mass: 407 (m/z+H)

Example #232

Preparation of N-(3,4-dimethoxyphenyl)-5-(2-fluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1031) 7-chloro-5-(2-fluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1032) exact mass: 365.1497 g/mol

(1033) HPLC-MS: analytical method A

(1034) rt: 2.64 min-found mass: 366 (m/z+H)

Example #233

Preparation of 5-(2-fluorophenyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1035) 7-chloro-5-(2-fluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1036) exact mass: 390.1868 g/mol

(1037) HPLC-MS: analytical method A

(1038) rt: 2.59 min-found mass: 391 (m/z+H)

Example #234

Preparation of N-(3,4-dimethoxyphenyl)-5-(3-fluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1039) 7-chloro-5-(3-fluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1040) exact mass: 365.1497 g/mol

(1041) HPLC-MS: analytical method A

(1042) rt: 3.01 min-found mass: 366 (m/z+H)

Example #235

Preparation of 5-(3-fluorophenyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1043) 7-chloro-5-(3-fluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1044) exact mass: 390.1868 g/mol

(1045) HPLC-MS: analytical method A

(1046) rt: 2.97 min-found mass: 391 (m/z+H)

Example #236

Preparation of 7-((5-(3-(methylthio)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3,4-dihydroquinolin-2(1H)-one

(1047) 7-chloro-2-(4-methoxybenzyl)-5-(3-(methylthio)phenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 7-amino-3,4-dihydroquinolin-2(1H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1048) exact mass: 402.1505 g/mol

(1049) HPLC-MS: analytical method D

(1050) rt: 5.89 min-found mass: 403 (m/z+H)

Example #237

Preparation of 3-(7-((4-(4-acetylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide

(1051) 3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide (0.16 mmol) and 1-(4-(4-aminophenyl)piperazin-1-yl)ethan-1-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1052) exact mass: 492.2033 g/mol

(1053) HPLC-MS: analytical method L

(1054) rt: 3.83 min-found mass: 493 (m/z+H)

Example #238

Preparation of 3-(7-((2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide

(1055) 3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide (0.16 mmol) and 7-amino-3,4-dihydroquinolin-2(1H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1056) exact mass: 435.1323 g/mol

(1057) HPLC-MS: analytical method L

(1058) rt: 3.91 min-found mass: 436 (m/z+H)

Example #239

Preparation of 3-(7-((4-morpholinophenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide

(1059) 3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide (0.16 mmol) and 4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1060) exact mass: 451.1718 g/mol

(1061) HPLC-MS: analytical method L

(1062) rt: 4.03 min-found mass: 452 (m/z+H)

Example #240

Preparation of 3-(7-((3-methoxy-4-morpholinophenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide

(1063) 3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide (0.16 mmol) and 3-methoxy-4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1064) exact mass: 481.1856 g/mol

(1065) HPLC-MS: analytical method L

(1066) rt: 3.99 min-found mass: 482 (m/z+H)

Example #241

Preparation of 4-(7-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoic acid

(1067) 4-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoic acid methyl ester (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. For the saponification the residue was dissolved in methanol. 2M aqueous NaOH-solution was added to ensure basic conditions. The mixture was irradiated in a microwave reactor for 10 min at 120° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1068) exact mass: 429.2249 g/mol

(1069) HPLC-MS: analytical method L

(1070) rt: 3.12 min-found mass: 430 (m/z+H)

Example #242

Preparation of methyl 4-(7-((4-morpholinophenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate

(1071) methyl 4-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate (0.16 mmol) and 4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1072) exact mass: 430.2067 g/mol

(1073) HPLC-MS: analytical method L

(1074) rt: 4.83 min-found mass: 431 (m/z+H)

Example #243

Preparation of 4-(7-((4-morpholinophenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoic acid

(1075) 4-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoic acid methyl ester (0.16 mmol) and 4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. For the saponification the residue was dissolved in methanol. 2M aqueous NaOH-solution was added to ensure basic conditions. The mixture was irradiated in a microwave reactor for 10 min at 120° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1076) exact mass: 416.1872 g/mol

(1077) HPLC-MS: analytical method L

(1078) rt: 4.07 min-found mass: 417 (m/z+H)

Example #244

Preparation of 4-(7-((3,4-dimethoxyphenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoic acid

(1079) 4-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoic acid methyl ester (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. For the saponification the residue was dissolved in methanol. 2M aqueous NaOH-solution was added to ensure basic conditions. The mixture was irradiated in a microwave reactor for 10 min at 120° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1080) exact mass: 391.1501 g/mol

(1081) HPLC-MS: analytical method L

(1082) rt: 4.14 min-found mass: 392 (m/z+H)

Example #245

Preparation of N-(2-methyl-1H-benzo[d]imidazol-5-yl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1083) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 2-methyl-1H-benzo[d]imidazol-5-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1084) exact mass: 347.1105 g/mol

(1085) HPLC-MS: analytical method D

(1086) rt: 3.80 min-found mass: 348 (m/z+H)

Example #246

Preparation of 1-(4-(4-((5-(3-(methylsulfonyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one

(1087) 7-chloro-2-(4-methoxybenzyl)-5-(3-(methylsulfonyl)phenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1-(4-(4-aminophenyl)piperazin-1-yl)ethan-1-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1088) exact mass: 491.2103 g/mol

(1089) HPLC-MS: analytical method L

(1090) rt: 4.09 min-found mass: 492 (m/z+H)

Example #247

Preparation of 5-(1H-indazol-6-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1091) 7-chloro-5-(1H-indazol-6-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1092) exact mass: 412.2036 g/mol

(1093) HPLC-MS: analytical method D

(1094) rt: 4.88 min-found mass: 413 (m/z+H)

Example #248

Preparation of 5-(1H-indazol-6-yl)-N-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1095) 7-chloro-5-(1H-indazol-6-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1096) exact mass: 425.2411 g/mol

(1097) HPLC-MS: analytical method D

(1098) rt: 3.53 min-found mass: 426 (m/z+H)

Example #249

Preparation of N-(3,4-dimethoxyphenyl)-5-(3-(methylsulfonyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1099) 7-chloro-2-(4-methoxybenzyl)-5-(3-(methylsulfonyl)phenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1100) exact mass: 425.1416 g/mol

(1101) HPLC-MS: analytical method L

(1102) rt: 4.38 min-found mass: 426 (m/z+H)

Example #250

Preparation of 7-((5-(3-(methylsulfonyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3,4-dihydroquinolin-2(1H)-one

(1103) 7-chloro-2-(4-methoxybenzyl)-5-(3-(methylsulfonyl)phenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 7-amino-3,4-dihydroquinolin-2(1H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1104) exact mass: 434.1393 g/mol

(1105) HPLC-MS: analytical method L

(1106) rt: 4.04 min-found mass: 435 (m/z+H)

Example #251

Preparation of 5-(3-(methylsulfonyl)phenyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1107) 7-chloro-2-(4-methoxybenzyl)-5-(3-(methylsulfonyl)phenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1108) exact mass: 450.1787 g/mol

(1109) HPLC-MS: analytical method L

(1110) rt: 4.35 min-found mass: 451 (m/z+H)

Example #252

Preparation of N-(2-methyl-1H-benzo[d]imidazol-5-yl)-5-(3-(methylsulfonyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1111) 7-chloro-2-(4-methoxybenzyl)-5-(3-(methylsulfonyl)phenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 2-methyl-1H-benzo[d]imidazol-5-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1112) exact mass: 419.1378 g/mol

(1113) HPLC-MS: analytical method L

(1114) rt: 3.21 min-found mass: 420 (m/z+H)

Example #253

Preparation of N,5-bis(3-(methylsulfonyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1115) 7-chloro-2-(4-methoxybenzyl)-5-(3-(methylsulfonyl)phenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3-(methylsulfonyl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1116) exact mass: 443.0937 g/mol

(1117) HPLC-MS: analytical method L

(1118) rt: 4.29 min-found mass: 444 (m/z+H)

Example #254

Preparation of N-(3-(methylsulfonyl)phenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1119) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3-(methylsulfonyl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1120) exact mass: 371.0664 g/mol

(1121) HPLC-MS: analytical method L

(1122) rt: 4.43 min-found mass: 372 (m/z+H)

Example #255

Preparation of 2-((3-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)sulfonyl)ethan-1-ol

(1123) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 2-((3-aminophenyl)sulfonyl)ethan-1-ol (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1124) exact mass: 401.0803 g/mol

(1125) HPLC-MS: analytical method L

(1126) rt: 4.12 min-found mass: 402 (m/z+H)

Example #256

Preparation of 1-(4-(4-((5-(1H-pyrrolo[3,2-b]pyridin-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)piperazin-1-yl)ethan-1-one

(1127) 7-chloro-2-(4-methoxybenzyl)-5-(1H-pyrrolo[3,2-b]pyridin-6-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1-(4-(4-aminophenyl)piperazin-1-yl)ethan-1-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1128) exact mass: 453.2351 g/mol

(1129) HPLC-MS: analytical method L

(1130) rt: 3.32 min-found mass: 454 (m/z+H)

Example #257

Preparation of 7-((5-(1H-pyrrolo[3,2-b]pyridin-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3,4-dihydroquinolin-2(1H)-one

(1131) 7-chloro-2-(4-methoxybenzyl)-5-(1H-pyrrolo[3,2-b]pyridin-6-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 7-amino-3,4-dihydroquinolin-2(1H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1132) exact mass: 396.1640 g/mol

(1133) HPLC-MS: analytical method CP

(1134) rt: 2.46 min-found mass: 397 (m/z+H)

Example #258

Preparation of N-(4-morpholinophenyl)-5-(1H-pyrrolo[3,2-b]pyridin-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1135) 7-chloro-2-(4-methoxybenzyl)-5-(1H-pyrrolo[3,2-b]pyridin-6-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1136) exact mass: 412.2036 g/mol

(1137) HPLC-MS: analytical method L

(1138) rt: 3.40 min-found mass: 413 (m/z+H)

Example #259

Preparation of N-(2-methyl-1H-benzo[d]imidazol-5-yl)-5-(1H-pyrrolo[3,2-b]pyridin-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1139) 7-chloro-2-(4-methoxybenzyl)-5-(1H-pyrrolo[3,2-b]pyridin-6-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 2-methyl-1H-benzo[d]imidazol-5-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1140) exact mass: 381.1626 g/mol

(1141) HPLC-MS: analytical method L

(1142) rt: 3.20 min-found mass: 382 (m/z+H)

Example #260

Preparation of N,N-dimethyl-4-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)benzenesulfonamide

(1143) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-amino-N,N-dimethylbenzenesulfonamide (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1144) exact mass: 400.0984 g/mol

(1145) HPLC-MS: analytical method L

(1146) rt: 4.90 min-found mass: 401 (m/z+H)

Example #261

Preparation of N-cyclopropyl-3-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)benzenesulfonamide

(1147) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3-amino-N-cyclopropylbenzenesulfonamide (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1148) exact mass: 412.0979 g/mol

(1149) HPLC-MS: analytical method L

(1150) rt: 4.74 min-found mass: 413 (m/z+H)

Example #262

Preparation of N-(3-(2H-1,2,3-triazol-2-yl)phenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1151) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3-(2H-1,2,3-triazol-2-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1152) exact mass: 360.1031 g/mol

(1153) HPLC-MS: analytical method D

(1154) rt: 6.78 min-found mass: 361 (m/z+H)

Example #263

Preparation of N-(4-(2H-1,2,3-triazol-2-yl)phenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1155) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(2H-1,2,3-triazol-2-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1156) exact mass: 360.1031 g/mol

(1157) HPLC-MS: analytical method L

(1158) rt: 5.10 min-found mass: 361 (m/z+H)

Example #264

Preparation of N,N-dimethyl-3-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)benzenesulfonamide

(1159) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3-amino-N,N-dimethylbenzenesulfonamide (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1160) exact mass: 400.0984 g/mol

(1161) HPLC-MS: analytical method A

(1162) rt: 2.93 min-found mass: 401 (m/z+H)

Example #265

Preparation of N-methyl-3-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)benzenesulfonamide

(1163) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3-amino-N-methylbenzenesulfonamide (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1164) exact mass: 386.0789 g/mol

(1165) HPLC-MS: analytical method A

(1166) rt: 2.68 min-found mass: 387 (m/z+H)

Example #266

Preparation of N-(3-(morpholinosulfonyl)phenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1167) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3-(morpholinosulfonyl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1168) exact mass: 442.1118 g/mol

(1169) HPLC-MS: analytical method A

(1170) rt: 2.87 min-found mass: 443 (m/z+H)

Example #267

Preparation of 5-(thiophen-2-yl)-N-(3-((trifluoromethyl)sulfonyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1171) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3-((trifluoromethyl)sulfonyl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1172) exact mass: 425.0301 g/mol

(1173) HPLC-MS: analytical method A

(1174) rt: 3.37 min-found mass: 426 (m/z+H)

Example #268

Preparation of N-(3-(methylsulfinyl)phenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1175) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3-(methylsulfinyl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1176) exact mass: 355.0720 g/mol

(1177) HPLC-MS: analytical method A

(1178) rt: 2.51 min-found mass: 356 (m/z+H)

Example #269

Preparation of 7-((5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)-3,4-dihydroquinolin-2(1H)-one

(1179) 7-chloro-5-(1H-indazol-6-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 7-amino-3,4-dihydroquinolin-2(1H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1180) exact mass: 396.1640 g/mol

(1181) HPLC-MS: analytical method D

(1182) rt: 4.76 min-found mass: 397 (m/z+H)

Example #270

Preparation of N-(3,4-dimethoxyphenyl)-5-(4-fluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1183) 7-chloro-5-(4-fluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1184) exact mass: 365.1497 g/mol

(1185) HPLC-MS: analytical method A

(1186) rt: 2.88 min-found mass: 366 (m/z+H)

Example #271

Preparation of 5-(4-fluorophenyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1187) 7-chloro-5-(4-fluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1188) exact mass: 390.1868 g/mol

(1189) HPLC-MS: analytical method A

(1190) rt: 2.83 min-found mass: 391 (m/z+H)

Example #272

Preparation of 5-(3,4-difluorophenyl)-N-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1191) 7-chloro-5-(3,4-difluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1192) exact mass: 383.1376 g/mol

(1193) HPLC-MS: analytical method A

(1194) rt: 3.15 min-found mass: 384 (m/z+H)

Example #273

Preparation of 5-(3,4-difluorophenyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1195) 7-chloro-5-(3,4-difluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1196) exact mass: 408.1747 g/mol

(1197) HPLC-MS: analytical method A

(1198) rt: 3.13 min-found mass: 409 (m/z+H)

Example #274

Preparation of 5-(3,5-difluorophenyl)-N-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1199) 7-chloro-5-(3,5-difluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1200) exact mass: 383.1376 g/mol

(1201) HPLC-MS: analytical method A

(1202) rt: 3.24 min-found mass: 384 (m/z+H)

Example #275

Preparation of 5-(2-fluorophenyl)-N-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1203) 7-chloro-5-(2-fluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-methylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1204) exact mass: 403.2245 g/mol

(1205) HPLC-MS: analytical method A

(1206) rt: 1.84 min-found mass: 404 (m/z+H)

Example #276

Preparation of 5-(2-fluorophenyl)-N-(3-(methylsulfonyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1207) 7-chloro-5-(2-fluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3-(methylsulfonyl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1208) exact mass: 383.1018 g/mol

(1209) HPLC-MS: analytical method A

(1210) rt: 2.63 min-found mass: 384 (m/z+H)

Example #277

Preparation of 5-(2-fluorophenyl)-N-(2-(methylsulfonyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1211) 7-chloro-5-(2-fluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 2-(methylsulfonyl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1212) exact mass: 383.1018 g/mol

(1213) HPLC-MS: analytical method A

(1214) rt: 2.89 min-found mass: 384 (m/z+H)

Example #278

Preparation of 5-(2-fluorophenyl)-N-(4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1215) 7-chloro-5-(2-fluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1216) exact mass: 486.3146 g/mol

(1217) HPLC-MS: analytical method A

(1218) rt: 2.00 min-found mass: 487 (m/z+H)

Example #279

Preparation of N-(4-(4-cyclopropylpiperazin-1-yl)phenyl)-5-(2-fluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1219) 7-chloro-5-(2-fluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-cyclopropylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1220) exact mass: 429.2434 g/mol

(1221) HPLC-MS: analytical method A

(1222) rt: 2.03 min-found mass: 430 (m/z+H)

Example #280

Preparation of N-(3,4-dimethoxyphenyl)-5-(1H-indazol-6-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1223) 7-chloro-5-(1H-indazol-6-yl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1224) exact mass: 387.1664 g/mol

(1225) HPLC-MS: analytical method D

(1226) rt: 4.93 min-found mass: 388 (m/z+H)

Example #281

Preparation of 5-(2,6-difluorophenyl)-N-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1227) 7-chloro-5-(2,6-difluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1228) exact mass: 383.1377 g/mol

(1229) HPLC-MS: analytical method A

(1230) rt: 2.71 min-found mass: 384 (m/z+H)

Example #282

Preparation of 5-(2,6-difluorophenyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1231) 7-chloro-5-(2,6-difluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1232) exact mass: 408.1747 g/mol

(1233) HPLC-MS: analytical method A

(1234) rt: 2.71 min-found mass: 409 (m/z+H)

Example #283

Preparation of N-(4-(4-cyclopropylpiperazin-1-yl)phenyl)-5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1235) 7-chloro-5-(2,6-difluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-cyclopropylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1236) exact mass: 447.2313 g/mol

(1237) HPLC-MS: analytical method A

(1238) rt: 2.07 min-found mass: 448 (m/z+H)

Example #284

Preparation of 5-(2,6-difluorophenyl)-N-(4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1239) 7-chloro-5-(2,6-difluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1240) exact mass: 504.3025 g/mol

(1241) HPLC-MS: analytical method A

(1242) rt: 1.97 min-found mass: 505 (m/z+H)

Example #285

Preparation of 5-(2,4-difluorophenyl)-N-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1243) 7-chloro-5-(2,4-difluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1244) exact mass: 383.1376 g/mol

(1245) HPLC-MS: analytical method A

(1246) rt: 2.83 min-found mass: 384 (m/z+H)

Example #286

Preparation of 5-(2,4-difluorophenyl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1247) 7-chloro-5-(2,4-difluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1248) exact mass: 408.1747 g/mol

(1249) HPLC-MS: analytical method A

(1250) rt: 2.79 min-found mass: 409 (m/z+H)

Example #287

Preparation of 6-(7-((2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one

(1251) 6-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (0.16 mmol) and 7-amino-3,4-dihydroquinolin-2(1H)-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1252) exact mass: 427.1598 g/mol

(1253) HPLC-MS: analytical method D

(1254) rt: 4.82 min-found mass: 428 (m/z+H)

Example #288

Preparation of 6-(7-((4-morpholinophenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one

(1255) 6-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (0.16 mmol) and 4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1256) exact mass: 443.1992 g/mol

(1257) HPLC-MS: analytical method D

(1258) rt: 4.96 min-found mass: 444 (m/z+H)

Example #289

Preparation of 6-(7-((2-methyl-1H-benzo[d]imidazol-5-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one

(1259) 6-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (0.16 mmol) and 2-methyl-1H-benzo[d]imidazol-5-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1260) exact mass: 412.1584 g/mol

(1261) HPLC-MS: analytical method D

(1262) rt: 3.81 min-found mass: 413 (m/z+H)

Example #290

Preparation of N-(4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1263) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1264) exact mass: 474.2791 g/mol

(1265) HPLC-MS: analytical method L

(1266) rt: 3.08 min-found mass: 475 (m/z+H)

Example #291

Preparation of N-(2-(methylsulfonyl)phenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1267) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 2-(methylsulfonyl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1268) exact mass: 371.0663 g/mol

(1269) HPLC-MS: analytical method L

(1270) rt: 4.94 min-found mass: 372 (m/z+H)

Example #292

Preparation of N-(3-((dimethylamino)methyl)phenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1271) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3-((dimethylamino)methyl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1272) exact mass: 350.1576 g/mol

(1273) HPLC-MS: analytical method L

(1274) rt: 3.33 min-found mass: 351 (m/z+H)

Example #293

Preparation of N-(4-(4-cyclopropylpiperazin-1-yl)phenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1275) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-(4-cyclopropylpiperazin-1-yl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1276) exact mass: 417.2081 g/mol

(1277) HPLC-MS: analytical method L

(1278) rt: 3.40 min-found mass: 418 (m/z+H)

Example #294

Preparation of morpholino(4-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)methanone

(1279) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and (4-aminophenyl)(morpholino)methanone (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1280) exact mass: 406.1454 g/mol

(1281) HPLC-MS: analytical method L

(1282) rt: 4.29 min-found mass: 407 (m/z+H)

Example #295

Preparation of N-(4-(morpholinomethyl)phenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1283) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and (4-Amino-phenyl)-morpholin-4-yl-methanone (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and dissolved in THF (dry) LiAlH4 powder was added (excess, 2 by 2 eq) until completion of reaction is observed (by LCMS). The reaction was quenched with water (1 mL per gram LiAlH4), then NaOH (ca. 15% aq., 1 mL per g LiAlH4), water (3 mL per gram LiAlH4). The mixture was filtered, washed with THF, MeOH, MeCN (ca. 10 mL each). The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1284) exact mass: 392.1710 g/mol

(1285) HPLC-MS: analytical method L

(1286) rt: 3.20 min-found mass: 393 (m/z+H)

Example #296

Preparation of N-(3-fluoro-4-morpholinophenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1287) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3-fluoro-4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1288) exact mass: 396.1393 g/mol

(1289) HPLC-MS: analytical method L

(1290) rt: 4.90 min-found mass: 397 (m/z+H)

Example #297

Preparation of (4-(4-methylpiperazin-1-yl)piperidin-1-yl)(4-((5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino)phenyl)methanone

(1291) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and (4-aminophenyl)(4-(4-methylpiperazin-1-yl)piperidin-1-yl)methanone (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1292) exact mass: 502.2731 g/mol

(1293) HPLC-MS: analytical method L

(1294) rt: 3.25 min-found mass: 503 (m/z+H)

Example #298

Preparation of 6-(7-((4-(4-acetylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one

(1295) 6-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (0.16 mmol) and 1-(4-(4-aminophenyl)piperazin-1-yl)ethan-1-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1296) exact mass: 484.2308 g/mol

(1297) HPLC-MS: analytical method A

(1298) rt: 2.22 min-found mass: 485 (m/z+H)

Example #299

Preparation of 6-(7-((3,4-dimethoxyphenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one

(1299) 6-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1300) exact mass: 418.1621 g/mol

(1301) HPLC-MS: analytical method A

(1302) rt: 2.41 min-found mass: 419 (m/z+H)

Example #300

Preparation of 5-(3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-N-(3,4-dimethoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1303) 6-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (0.16 mmol) and 3,4-dimethoxyaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The reaction mixture was dissolved in THF (dry) LiAlH4 powder was added (excess, 2 by 2 eq) until completion of reaction is observed (by LCMS). The reaction was quenched with water (1 mL per gram LiAlH4), then NaOH (ca. 15% aq., 1 mL per g LiAlH4), water (3 mL per gram LiAlH4). The mixture was filtered, washed with THF, MeOH, MeCN (ca. 10 mL each). The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1304) exact mass: 404.1877 g/mol

(1305) HPLC-MS: analytical method L

(1306) rt: 3.84 min-found mass: 405 (m/z+H)

Example #301

Preparation of 5-(3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-N-(4-morpholinophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1307) 6-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (0.16 mmol) and 4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The reaction mixture was dissolved in THF (dry) LiAlH4 powder was added (excess, 2 by 2 eq) until completion of reaction is observed (by LCMS). The reaction was quenched with water (1 mL per gram LiAlH4), then NaOH (ca. 15% aq., 1 mL per g LiAlH4), water (3 mL per gram LiAlH4). The mixture was filtered, washed with THF, MeOH, MeCN (ca. 10 mL each). The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1308) exact mass: 429.2248 g/mol

(1309) HPLC-MS: analytical method L

(1310) rt: 3.81 min-found mass: 430 (m/z+H)

Example #302

Preparation of 5-(3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-N-(2-methyl-1H-benzo[d]imidazol-5-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1311) 6-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (0.16 mmol) and 2-methyl-1H-benzo[d]imidazol-5-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The reaction mixture was dissolved in THF (dry) LiAlH4 powder was added (excess, 2 by 2 eq) until completion of reaction is observed (by LCMS). The reaction was quenched with water (1 mL per gram LiAlH4), then NaOH (ca. 15% aq., 1 mL per g LiAlH4), water (3 mL per gram LiAlH4). The mixture was filtered, washed with THF, MeOH, MeCN (ca. 10 mL each). The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1312) exact mass: 398.1840 g/mol

(1313) HPLC-MS: analytical method L

(1314) rt: 3.09 min-found mass: 399 (m/z+H)

Example #303

Preparation of N-(2-methylisoindolin-5-yl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1315) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 2-methylisoindolin-5-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1316) exact mass: 348.1375 g/mol

(1317) HPLC-MS: analytical method L

(1318) rt: 3.03 min-found mass: 349 (m/z+H)

Example #304

Preparation of N-(1,3-dihydroisobenzofuran-5-yl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1319) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 1,3-dihydroisobenzofuran-5-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1320) exact mass: 335.0999 g/mol

(1321) HPLC-MS: analytical method L

(1322) rt: 4.61 min-found mass: 336 (m/z+H)

Example #305

Preparation of N-(3-(tert-butyl)phenyl)-5-(thiophen-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1323) 7-chloro-2-(4-methoxybenzyl)-5-(thiophen-2-yl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3-(tert-butyl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1324) exact mass: 349.1646 g/mol

(1325) HPLC-MS: analytical method L

(1326) rt: 5.75 min-found mass: 350 (m/z+H)

Example #306

Preparation of methyl 3-(7-((4-(4-acetylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate

(1327) methyl 3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate (0.16 mmol) and 1-(4-(4-aminophenyl)piperazin-1-yl)ethan-1-one (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1328) exact mass: 471.2382 g/mol

(1329) HPLC-MS: analytical method D

(1330) rt: 5.83 min-found mass: 482 (m/z+H)

Example #307

Preparation of methyl 3-(7-((1H-indazol-6-yl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate

(1331) methyl 3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate (0.16 mmol) and 1H-indazol-6-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1332) exact mass: 385.1464 g/mol

(1333) HPLC-MS: analytical method D

(1334) rt: 5.91 min-found mass: 386 (m/z+H)

Example #308

Preparation of methyl 3-(7-((4-morpholinophenyl)amino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate

(1335) methyl 3-(7-chloro-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidin-5-yl)benzoate (0.16 mmol) and 4-morpholinoaniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1336) exact mass: 430.2067 g/mol

(1337) HPLC-MS: analytical method D

(1338) rt: 6.26 min-found mass: 431 (m/z+H)

Example #309

Preparation of 5-(3-aminophenyl)-N-(4-((dimethylamino)methyl)phenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1339) 7-Chloro-2-(4-methoxy-benzyl)-5-(3-nitro-phenyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-((dimethylamino)methyl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The reaction mixture was dissolved in methanol (3 mL). Pd/C was added (20 mg) and the reaction was stirred overnight under N2 at room temperature. After filtration with celite the reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1340) exact mass: 359.2176 g/mol

(1341) HPLC-MS: analytical method D

(1342) rt: 0.63 min-found mass: 360 (m/z+H)

Example #310

Preparation of 5-(2-fluorophenyl)-N-(2-methylisoindolin-5-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1343) 7-chloro-5-(2-fluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 2-methylisoindolin-5-amine (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1344) exact mass: 360.1729 g/mol

(1345) HPLC-MS: analytical method C

(1346) rt: 2.00 min-found mass: 409 (m/z+H)

Example #311

Preparation of N-(4-((dimethylamino)methyl)phenyl)-5-(2-fluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1347) 7-chloro-5-(2-fluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 4-((dimethylamino)methyl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1348) exact mass: 362.1930 g/mol

(1349) HPLC-MS: analytical method C

(1350) rt: 2.17 min-found mass: 361 (m/z+H)

Example #312

Preparation of N-(3-((dimethylamino)methyl)phenyl)-5-(2-fluorophenyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine

(1351) 7-chloro-5-(2-fluorophenyl)-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine (0.16 mmol) and 3-((dimethylamino)methyl)aniline (0.3 mmol 2 eq.) were suspended in MeOH (dry, 3 mL) in a microwave vial (2-5 mL), HCl in dioxane (4M, 3 drops) was added. The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was evaporated and used without further purification. The residue was dissolved in TFA (3 mL). The reaction mixture was irradiated in a microwave reactor for 5 min at 140° C. The reaction mixture was concentrated and purified by semi-preparative HPLC-MS and freeze dried from water/t-BuOH 4/1.

(1352) exact mass: 362.1930 g/mol

(1353) HPLC-MS: analytical method C

(1354) rt: 2.18 min-found mass: 363 (m/z+H)

(1355) Biological Data

(1356) SYK Activities:

(1357) Ki lower than 10 nM:

(1358) Example #1; Example #2; Example #4; Example #5; Example #6; Example #7; Example #10; Example #11; Example #16; Example #20; Example #23; Example #25; Example #30; Example #31; Example #33; Example #34; Example #35; Example #36; Example #46; Example #54; Example #58; Example #59; Example #60; Example #61; Example #62; Example #63; Example #64; Example #66; Example #67; Example #68; Example #69; Example #70; Example #71; Example #72; Example #73; Example #74; Example #75; Example #76; Example #78; Example #79; Example #82; Example #84; Example #87; Example #91; Example #95; Example #98; Example #99; Example #117; Example #118; Example #119; Example #128; Example #131; Example #132; Example #134; Example #137; Example #138; Example #143; Example #144; Example #149; Example #151; Example #160; Example #161; Example #162; Example #163; Example #164; Example #169; Example #170; Example #172; Example #175; Example #179; Example #182; Example #183; Example #184; Example #186; Example #187; Example #188; Example #189; Example #190; Example #191; Example #192; Example #193; Example #194; Example #195; Example #196; Example #197; Example #198; Example #200; Example #201; Example #203; Example #204; Example #205; Example #206; Example #207; Example #208; Example #213; Example #225; Example #232; Example #233; Example #234; Example #235; Example #237; Example #238; Example #239; Example #240; Example #241; Example #243; Example #244; Example #245; Example #246; Example #247; Example #248; Example #251; Example #256; Example #257; Example #269; Example #275; Example #278; Example #280; Example #281; Example #285; Example #290; Example #293; Example #295; Example #296; Example #297; Example #298; Example #300; Example #302; Example #303; Example #304;
Ki between 10 nM and 100 nM:
Example #3; Example #8; Example #9; Example #12; Example #14; Example #17; Example #18; Example #19; Example #22; Example #24; Example #26; Example #27; Example #28; Example #29; Example #32; Example #37; Example #38; Example #40; Example #47; Example #50; Example #51; Example #52; Example #53; Example #57; Example #65; Example #77; Example #80; Example #81; Example #83; Example #85; Example #86; Example #89; Example #90; Example #92; Example #93; Example #94; Example #96; Example #97; Example #100; Example #101; Example #102; Example #103; Example #104; Example #105; Example #106; Example #107; Example #108; Example #109; Example #110; Example #111; Example #112; Example #114; Example #116; Example #120; Example #122; Example #123; Example #124; Example #125; Example #126; Example #127; Example #129; Example #135; Example #136; Example #139; Example #140; Example #141; Example #142; Example #145; Example #146; Example #147; Example #152; Example #156; Example #157; Example #158; Example #159; Example #165; Example #166; Example #167; Example #168; Example #171; Example #173; Example #176; Example #177; Example #180; Example #181; Example #185; Example #199; Example #202; Example #209; Example #210; Example #211; Example #212; Example #216; Example #218; Example #220; Example #221; Example #223; Example #226; Example #227; Example #228; Example #229; Example #230; Example #231; Example #236; Example #242; Example #249; Example #252; Example #253; Example #254; Example #258; Example #260; Example #268; Example #270; Example #271; Example #273; Example #276; Example #279; Example #282; Example #283; Example #284; Example #286; Example #287; Example #288; Example #289; Example #291; Example #294; Example #299; Example #301; Example #306; Example #309; Example #310; Example #311;
Ki between 100 nM and 1000 nM:
Example #13; Example #21; Example #39; Example #45; Example #48; Example #55; Example #56; Example #88; Example #113; Example #115; Example #121; Example #130; Example #133; Example #148; Example #150; Example #153; Example #174; Example #178; Example #215; Example #217; Example #219; Example #222; Example #224; Example #255; Example #259; Example #262; Example #263; Example #264; Example #265; Example #266; Example #267; Example #272; Example #274; Example #277; Example #292; Example #305; Example #307; Example #312;
LRRK2 Activities:
IC50 lower than 10 nM:
Example #36; Example #82; Example #135; Example #144; Example #247; Example #269;
IC50 between 10 nM and 100 nM:
Example #23; Example #26; Example #37; Example #46; Example #59; Example #62; Example #64; Example #69; Example #70; Example #71; Example #72; Example #73; Example #75; Example #76; Example #77; Example #79; Example #84; Example #87; Example #89; Example #91; Example #95; Example #117; Example #118; Example #136; Example #137; Example #139; Example #143; Example #145; Example #147; Example #158; Example #161; Example #164; Example #166; Example #182; Example #183; Example #184; Example #185; Example #190; Example #195; Example #199; Example #206; Example #235; Example #238; Example #280; Example #297;
IC50 between 100 nM and 1000 nM:
Example #1; Example #2; Example #4; Example #5; Example #6; Example #7; Example #9; Example #10; Example #14; Example #16; Example #17; Example #18; Example #20; Example #21; Example #22; Example #24; Example #25; Example #27; Example #28; Example #32; Example #33; Example #34; Example #35; Example #40; Example #41; Example #47; Example #48; Example #50; Example #51; Example #58; Example #60; Example #61; Example #63; Example #65; Example #66; Example #67; Example #68; Example #74; Example #78; Example #80; Example #81; Example #83; Example #85; Example #86; Example #88; Example #93; Example #96; Example #97; Example #99; Example #101; Example #108; Example #109; Example #110; Example #111; Example #114; Example #119; Example #120; Example #126; Example #127; Example #131; Example #132; Example #134; Example #138; Example #140; Example #142; Example #146; Example #156; Example #157; Example #159; Example #162; Example #163; Example #169; Example #170; Example #171; Example #172; Example #173; Example #179; Example #186; Example #187; Example #188; Example #189; Example #191; Example #193; Example #194; Example #196; Example #197; Example #198; Example #200; Example #201; Example #202; Example #203; Example #204; Example #205; Example #207; Example #208; Example #209; Example #218; Example #225; Example #232; Example #233; Example #234; Example #237; Example #239; Example #240; Example #248; Example #251; Example #254; Example #257; Example #261; Example #265; Example #268; Example #271; Example #275; Example #278; Example #279; Example #281; Example #282; Example #283; Example #284; Example #290; Example #293; Example #294; Example #295; Example #296; Example #300; Example #301; Example #302; Example #303; Example #304; Example #310; Example #311;
MYLK Activities:
IC50 lower than 5000 nM:
Example #5; Example #8; Example #20; Example #21; Example #34; Example #35; Example #45; Example #46; Example #57; Example #58; Example #62; Example #68; Example #70; Example #74; Example #83; Example #91; Example #95; Example #97; Example #99; Example #114; Example #117; Example #118; Example #120; Example #127; Example #131; Example #132; Example #134; Example #138; Example #139; Example #143; Example #144; Example #147; Example #160; Example #161; Example #163; Example #172; Example #175; Example #179; Example #182; Example #187; Example #188; Example #189; Example #190; Example #191; Example #225; Example #238; Example #240; Example #241; Example #247; Example #248; Example #252; Example #254; Example #255; Example #268; Example #275; Example #276; Example #277; Example #279; Example #280; Example #284; Example #286; Example #288; Example #289; Example #290; Example #293; Example #294; Example #295;

(1359) FIG. 1 shows the LAD2-SYK Correlation