Herbicidal compounds

Abstract

The present invention relates to a compound of formula (I) wherein: wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11 and G are as defined herein; and wherein the compound of formula (I) is optionally present as an agrochemically acceptable salt thereof. These compounds are thought to be suitable for use as herbicides. The invention therefore also relates to a method of controlling weeds, especially grassy monocotyledonous weeds, in crops of useful plants, comprising applying a compound of formula (I), or a herbicidal composition comprising such a compound, to the plants or to the locus thereof. ##STR00001##

Claims

1. A compound of formula (I): ##STR00160## or an agrochemically acceptable salt thereof wherein: R.sup.1 is selected from the group consisting of methyl, ethyl, n-propyl, cyclopropyl, trifluoromethyl, vinyl, ethynyl, fluorine, chlorine, bromine, methoxy, ethoxy and fluoromethoxy; R.sup.2 is selected from the group consisting of hydrogen, methyl, ethyl, n-propyl, isopropyl, cyclopropyl, fluoromethyl, fluoroethyl, vinyl, prop-1-enyl, ethynyl, prop-1-ynyl, 2-chloroethynyl, 2-fluoroethynyl, 2-(trifluoromethyl)ethynyl, but-1-ynyl, 2-(cyclopropyl)ethynyl, halogen, methoxy, prop-2-ynyloxy, and (C.sub.1-C.sub.2fluoroalkyl)-methoxy-; or R.sup.2 is phenyl optionally substituted by 1, 2 or 3 of, independently, halogen, C.sub.1-C.sub.2alkyl, C.sub.1-C.sub.2fluoroalkyl, C.sub.1-C.sub.2alkoxy, C.sub.1-C.sub.2fluoroalkoxy, cyano or nitro; or R.sup.2 is monocyclic heteroaryl optionally substituted by 1, 2 or 3 of, independently, halogen, C.sub.1-C.sub.2alkyl, C.sub.1-C.sub.2fluoroalkyl, C.sub.1-C.sub.2alkoxy, C.sub.1-C.sub.2fluoroalkoxy, cyano or nitro; and R.sup.3 is selected from the group consisting of hydrogen, methyl, ethyl, n-propyl, cyclopropyl, trifluoromethyl, vinyl, ethynyl, fluorine, chlorine, bromine, methoxy, ethoxy, n-propoxy, isopropoxy, C.sub.1-C.sub.2fluoroalkoxy, C.sub.1-C.sub.2alkoxy-C.sub.1-C.sub.3alkoxy- and C.sub.1fluoroalkoxy-C.sub.1-C.sub.3alkoxy-; R.sup.4, R.sup.5 and R.sup.6 are independently of each other, selected from the group consisting of hydrogen, C.sub.1-C.sub.5alkyl, C.sub.2-C.sub.3 alkenyl, C.sub.2-C.sub.3alkynyl, C.sub.1-C.sub.2fluoroalkyl and C.sub.1-C.sub.2alkoxyC.sub.1-C.sub.2alkyl; R.sup.7 and R.sup.8 are independently of each other, selected from the group consisting of hydrogen, fluorine and C.sub.1-C.sub.3alkyl; R.sup.9 and R.sup.19 are independently of each other, selected from the group consisting of hydrogen, fluorine and C.sub.1-C.sub.3alkyl; R.sup.11 is (CO)-5,5-dimethyl-4H-isoxazol-2-yl, R.sup.12 is selected from the group consisting of hydrogen, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6alkoxy and hydroxy; and wherein: G is hydrogen; an agriculturally acceptable metal, or an agriculturally acceptable sulfonium or ammonium group; or G is C(X.sup.a)R.sup.a, C(X.sup.b)X.sup.cR.sup.b, C(X.sup.d)N(R.sup.c)R.sup.d, SO.sub.2R.sup.e, P(X.sup.e)(R.sup.f)R.sup.9, CH.sub.2X.sup.fR.sup.h, or CH(Me)-X.sup.fR.sup.h; or phenyl-CH.sub.2 or phenyl-CH(C.sub.1-C.sub.2alkyl)- (in each of which the phenyl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.2alkyl, C.sub.1fluoroalkyl, C.sub.1-C.sub.2alkoxy, C.sub.1fluoroalkoxy, fluorine, chlorine, bromine, cyano or nitro), or heteroaryl-CH.sub.2 or heteroaryl-CH(C.sub.1-C.sub.2alkyl)- (in each of which the heteroaryl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.2alkyl, C.sub.1fluoroalkyl, C.sub.1-C.sub.2alkoxy, C.sub.1fluoroalkoxy, fluorine, chlorine, bromine, cyano or nitro), or phenyl-C(O)CH.sub.2 (wherein the phenyl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.2alkyl, C.sub.1fluoroalkyl, C.sub.1-C.sub.2alkoxy, C.sub.1fluoroalkoxy, fluorine, chlorine, bromine, cyano or nitro); or C.sub.1-C.sub.6alkoxy-C(O)CH.sub.2, C.sub.1-C.sub.6alkyl-C(O)CH.sub.2, C.sub.1-C.sub.6alkoxy-C(O)CHCH, C.sub.2-C.sub.7alken-1-yl-CH.sub.2, C.sub.2-C.sub.7alken-1-yl-CH(C.sub.1-C.sub.2alkyl)-, C.sub.2-C.sub.4fluoroalken-1-yl-CH.sub.2, C.sub.2-C.sub.7alkyn-1-yl-CH.sub.2, or C.sub.2-C.sub.7alkyn-1-yl-CH(C.sub.1-C.sub.2alkyl)-; wherein X.sup.a, X.sup.b, X.sup.d, X.sup.e and X.sup.f are independently of each other oxygen or sulfur; and wherein R.sup.a is H, C.sub.1-C.sub.21alkyl, C.sub.2-C.sub.21alkenyl, C.sub.2-C.sub.18alkynyl, C.sub.1-C.sub.10fluoroalkyl, C.sub.1-C.sub.10cyanoalkyl, C.sub.1-C.sub.10nitroalkyl, C.sub.1-C.sub.10aminoalkyl, C.sub.1-C.sub.5alkylamino(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8dialkylamino(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.7cycloalkyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkoxy(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.5alkenyloxy(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.5alkynyloxy(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylthio(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylsulfinyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylsulfonyl(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8alkylideneaminoxy(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylcarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkoxycarbonyl(C.sub.1-C.sub.5)alkyl, aminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylaminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8dialkylaminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylcarbonylamino(C.sub.1-C.sub.5)alkyl, N(C.sub.1-C.sub.5)alkylcarbonyl-N(C.sub.1-C.sub.5)alkylamino(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.6trialkylsilyl(C.sub.1-C.sub.5)alkyl, phenyl(C.sub.1-C.sub.5)alkyl (wherein the phenyl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, halogen, cyano, or nitro), heteroaryl(C.sub.1-C.sub.5)alkyl (wherein the heteroaryl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfonyl, halogen, cyano, or nitro), C.sub.2-C.sub.5fluoroalkenyl, C.sub.3-C.sub.8cycloalkyl; phenyl or phenyl substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; or heteroaryl or heteroaryl substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; R.sup.b is C.sub.1-C.sub.18alkyl, C.sub.3-C.sub.18alkenyl, C.sub.3-C.sub.18alkynyl, C.sub.2-C.sub.10fluoroalkyl, C.sub.1-C.sub.10cyanoalkyl, C.sub.1-C.sub.10nitroalkyl, C.sub.2-C.sub.10aminoalkyl, C.sub.1-C.sub.5alkylamino(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8dialkylamino(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.7cycloalkyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkoxy(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.5alkenyloxy(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.5alkynyloxy(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylthio(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylsulfinyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylsulfonyl(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8alkylideneaminoxy(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylcarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkoxycarbonyl(C.sub.1-C.sub.5)alkyl, aminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylaminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8dialkylaminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylcarbonylamino(C.sub.1-C.sub.5)alkyl, N(C.sub.1-C.sub.5)alkylcarbonyl-N(C.sub.1-C.sub.5)alkylamino(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.6trialkylsilyl(C.sub.1-C.sub.5)alkyl, phenyl(C.sub.1-C.sub.5)alkyl (wherein the phenyl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, halogen, cyano, or nitro), heteroarylC.sub.1-C.sub.5alkyl (wherein the heteroaryl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, C.sub.1-C.sub.3alkyl-thio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, halogen, cyano, or nitro), C.sub.3-C.sub.5fluoroalkenyl, C.sub.3-C.sub.8cycloalkyl; phenyl or phenyl substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; or heteroaryl or heteroaryl substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; and R.sup.c and R.sup.d are each independently of each other hydrogen, C.sub.1-C.sub.10alkyl, C.sub.3-C.sub.10alkenyl, C.sub.3-C.sub.10alkynyl, C.sub.2-C.sub.10fluoroalkyl, C.sub.1-C.sub.10cyanoalkyl, C.sub.1-C.sub.10nitroalkyl, C.sub.1-C.sub.10aminoalkyl, C.sub.1-C.sub.5alkylamino(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8dialkylamino(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.7cycloalkyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkoxy(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.5alkenyloxy(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.5alkynyloxy(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylthio(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylsulfinyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylsulfonyl(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8alkylideneaminoxy(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylcarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkoxycarbonyl(C.sub.1-C.sub.5)alkyl, aminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylaminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8dialkylaminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylcarbonylamino(C.sub.1-C.sub.5)alkyl, N(C.sub.1-C.sub.5)alkylcarbonyl-N(C.sub.2-C.sub.5)alkylaminoalkyl, C.sub.3-C.sub.6trialkylsilyl(C.sub.1-C.sub.5)alkyl, phenyl(C.sub.1-C.sub.5)alkyl (wherein the phenyl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, halogen, cyano, or nitro), heteroaryl(C.sub.1-C.sub.5)alkyl (wherein the heteroaryl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, halogen, cyano, or nitro), C.sub.2-C.sub.5fluoroalkenyl, C.sub.3-C.sub.8cycloalkyl; phenyl or phenyl substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; heteroaryl or heteroaryl substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; heteroarylamino or heteroarylamino substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; diheteroarylamino or diheteroarylamino substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; phenylamino or phenylamino substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or by nitro; diphenylamino or diphenylamino substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; or C.sub.3-C.sub.7cycloalkylamino, di(C.sub.3-C.sub.7cycloalkyl)amino or C.sub.3-C.sub.7cycloalkoxy; or R.sup.c and R.sup.d, together with the nitrogen to which they are bonded, form an unsubstituted 4, 5, 6 or 7 membered ring, optionally containing one heteroatom selected from O or S; and R.sup.e is C.sub.1-C.sub.10alkyl, C.sub.2-C.sub.10alkenyl, C.sub.2-C.sub.10alkynyl, C.sub.1-C.sub.10fluoroalkyl, C.sub.1-C.sub.10cyanoalkyl, C.sub.1-C.sub.10nitroalkyl, C.sub.1-C.sub.10aminoalkyl, C.sub.1-C.sub.5alkylamino(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8dialkylamino(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.7cycloalkyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkoxy(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.5alkenyloxy(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.5alkynyloxy(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylthio(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylsulfinyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylsulfonyl(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8alkylideneaminoxy(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylcarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkoxycarbonyl(C.sub.1-C.sub.5)alkyl, aminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylaminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8dialkylaminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylcarbonylamino(C.sub.1-C.sub.5)alkyl, N(C.sub.1-C.sub.5)alkylcarbonyl-N(C.sub.1-C.sub.5)alkylamino(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.6trialkylsilyl(C.sub.1-C.sub.5)alkyl, phenyl(C.sub.1-C.sub.5)alkyl (wherein the phenyl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, halogen, cyano, or nitro), heteroaryl(C.sub.1-C.sub.5)alkyl (wherein the heteroaryl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, halogen, cyano, or nitro), C.sub.2-C.sub.5fluoroalkenyl, C.sub.3-C.sub.8cycloalkyl; phenyl or phenyl substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; heteroaryl or heteroaryl substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; heteroarylamino or heteroarylamino substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; diheteroarylamino or diheteroarylamino substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; phenylamino or phenylamino substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; diphenylamino or diphenylamino substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; or C.sub.3-C.sub.7cycloalkylamino, di(C.sub.3-C.sub.7cycloalkyl)amino, C.sub.3-C.sub.7cycloalkoxy, C.sub.1-C.sub.10alkoxy, C.sub.1-C.sub.10fluoroalkoxy, C.sub.1-C.sub.5alkylamino or di(C.sub.1-C.sub.4alkyl)amino; R.sup.f and R.sup.g are are each independently of each other C.sub.1-C.sub.10alkyl, C.sub.2-C.sub.10alkenyl, C.sub.2-C.sub.10alkynyl, C.sub.1-C.sub.10alkoxy, C.sub.1-C.sub.10fluoroalkyl, C.sub.1-C.sub.10cyanoalkyl, C.sub.1-C.sub.10nitroalkyl, C.sub.1-C.sub.10aminoalkyl, C.sub.1-C.sub.5alkylamino(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8dialkylamino(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.7cycloalkyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkoxy(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.5alkenyloxy(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.5alkynyloxy(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylthio(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylsulfinyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylsulfonyl(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8alkylideneaminoxy(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylcarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkoxycarbonyl(C.sub.1-C.sub.5)alkyl, aminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylaminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8dialkylaminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylcarbonylamino(C.sub.1-C.sub.5)alkyl, N(C.sub.1-C.sub.5)alkylcarbonyl-N(C.sub.2-C.sub.5)alkylaminoalkyl, C.sub.3-C.sub.6trialkylsilyl(C.sub.1-C.sub.5)alkyl, phenyl(C.sub.1-C.sub.5)alkyl (wherein the phenyl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, halogen, cyano, or nitro), heteroaryl(C.sub.1-C.sub.5)alkyl (wherein the heteroaryl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, halogen, cyano, or nitro), C.sub.2-C.sub.5fluoroalkenyl, C.sub.3-C.sub.8cycloalkyl; phenyl or phenyl substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; heteroaryl or heteroaryl substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; heteroarylamino or heteroarylamino substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; diheteroarylamino or diheteroarylamino substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; diphenylamino or diphenylamino substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; or C.sub.3-C.sub.7cycloalkylamino, di(C.sub.3-C.sub.7cycloalkyl)amino, C.sub.3-C.sub.7cycloalkoxy, C.sub.1-C.sub.10fluoroalkoxy, C.sub.1-C.sub.5alkylamino or di(C.sub.1-C.sub.4alkyl)amino; or benzyloxy or phenoxy, wherein the benzyl and phenyl groups are in turn optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; and R.sup.h is C.sub.1-C.sub.10alkyl, C.sub.3-C.sub.10alkenyl, C.sub.3-C.sub.10alkynyl, C.sub.1-C.sub.10fluoroalkyl, C.sub.1-C.sub.10cyanoalkyl, C.sub.1-C.sub.10nitroalkyl, C.sub.2-C.sub.10aminoalkyl, C.sub.1-C.sub.5alkylamino(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.8dialkylamino(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.7cycloalkyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkoxy(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.5alkenyloxy(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.5alkynyloxy(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylthio(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylsulfinyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylsulfonyl(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8alkylideneaminoxy(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylcarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkoxycarbonyl(C.sub.1-C.sub.5)alkyl, aminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylaminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8dialkylaminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylcarbonylamino(C.sub.1-C.sub.5)alkyl, N(C.sub.1-C.sub.5)alkylcarbonyl-N(C.sub.1-C.sub.5)alkylamino(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.6trialkylsilyl(C.sub.1-C.sub.5)alkyl, phenyl(C.sub.1-C.sub.5)alkyl (wherein the phenyl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3 alkylsulfonyl, halogen, cyano or nitro), heteroaryl(C.sub.1-C.sub.5)alkyl (wherein the heteroaryl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3 alkylsulfonyl, halogen, cyano or nitro), phenoxy(C.sub.1-C.sub.5)alkyl (wherein the phenyl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3 alkylsulfonyl, halogen, cyano or nitro), heteroaryloxy(C.sub.1-C.sub.5)alkyl (wherein the heteroaryl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3 alkylsulfonyl, halogen, cyano or nitro), C.sub.3-C.sub.5fluoroalkenyl, C.sub.3-C.sub.8cycloalkyl; phenyl or phenyl substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; heteroaryl or heteroaryl substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; C.sub.1-C.sub.6alkyl-C(O); C.sub.1-C.sub.6alkoxy-C(O); or phenyl-C(O) wherein the phenyl is optionally substituted by 1 or 2 of, independently, C.sub.1-C.sub.2alkyl, C.sub.1fluoroalkyl, C.sub.1-C.sub.2alkoxy, C.sub.1fluoroalkoxy, fluorine, chlorine, bromine, cyano or nitro.

2. The compound according to claim 1, wherein G is hydrogen.

3. The compound according to claim 1, wherein R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9 and R.sup.10 are hydrogen.

4. The compound according to claim 1, wherein R.sup.2 is selected from the group consisting of methyl, prop-1-ynyl and an optionally substituted monocyclic heteroaryl selected from the group consisting of R.sup.2a and R.sup.2b: ##STR00161## in which: X.sup.1 is N or CH; X.sup.2 is N or CR.sup.a; R.sup.a is selected from the group consisting of hydrogen, fluorine, chlorine and C.sub.1fluoroalkyl; R.sup.b is selected from the group consisting of hydrogen, fluorine, chlorine and C.sub.1fluoroalkyl; R.sup.b is selected from the group consisting of hydrogen, fluorine, chlorine, bromine, methyl, C.sub.1fluoroalkyl and cyano; and R.sup.d is selected from the group consisting of hydrogen, fluorine, chlorine, bromine, methyl, C.sub.1fluoroalkyl and cyano.

5. The compound according to claim 1, wherein R.sup.1 and R.sup.3 are methyl.

6. The compound according to claim 1, wherein R.sup.1 is methyl, R.sup.2 is methyl and R.sup.3 is methyl.

7. The compound of claim 1, wherein the compound of formula (I) is a compound of formula (Ia): ##STR00162## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11, R.sup.12 and G are as defined therein.

8. The compound according to claim 7, wherein, more than 50% by molarity of the compound of formula (Ia) has the indicated stereochemistry at the ring-carbon atom bonded to R.sup.6 and CR.sup.7R.sup.8CR.sup.9R.sup.10NR.sup.11R.sup.12.

9. A herbicidal composition which comprises a compound of formula (I) as defined in claim 1, and an agrochemically acceptable carrier, diluent and/or solvent.

10. The herbicidal composition according to claim 9, which comprises one or more further herbicides and/or a safener.

11. A method of controlling grassy monocotyledonous weeds in crops of useful plants, comprising applying a herbicidal composition according to claim 9, to the weeds or to the locus thereof.

Description

PREPARATION EXAMPLES

(1) Those skilled in the art will appreciate that certain compounds described below are 8-ketoenols, and as such may exist as a single tautomer or as a mixture of keto-enol and diketone tautomers, as described, for example by J. March, Advanced Organic Chemistry, third edition, John Wiley and Sons. The compounds shown below, and in Tables A1, A2, A3 or P1 below, are usually drawn as an arbitrary single enol tautomer, but it should be inferred that this description covers both the diketone form and any possible enols which could arise through tautomerism. Where more than one tautomer is observed in proton NMR (.sup.1H NMR), the data shown are for the mixture of tautomers. Furthermore, some of the compounds shown below are drawn as single enantiomers for the purposes of simplicity, but unless specified as single enantiomers, these structures should be construed as representing a mixture of enantiomers. Additionally, some of the compounds can exist as diastereoisomers, and it should be inferred that these can be present as a mixture of diastereoisomers or as any possible single diastereoisomer. Within the detailed experimental section the diketone tautomer is chosen for naming purposes, even if the predominant tautomer is the enol form.

Abbreviations Used Herein

(2) DCM-dichloromethane

(3) DMF-N,N-dimethylformamide

(4) DMSO-dimethyl sulfoxide

(5) EDTA-ethylenediaminetetraacetic acid

(6) Hunig's base-N,N-diisopropylethylamine

(7) LDA-lithium diisopropylamide

(8) LiHMDS-lithium hexamethyldisilazide, also called lithium 1,1,1,3,3,3-hexamethyldisilazan-2-ide, or lithium bis(trimethylsilyl)amide

(9) PTFE-polytetrafluoroethylene

(10) SPhos (S-Phos)-2-(dicyclohexylphosphino)-2,6-dimethoxybiphenyl

(11) TFA-trifluoroacetic acid

(12) THF-tetrahydrofuran

(13) RT-room temperature (typically ca. 15-30 C. such as ca. 18-25 C.)

(14) HPLC-high performance (or high pressure) liquid chromatography

(15) MS-mass spectrometry

(16) NMR-nuclear magnetic resonance

(17) within .sup.1H NMR spectral data given herein: s=singlet, d=doublet, t=triplet, q=quartet, dd=doublet of doublets, m=multiplet, br.=broad

(18) SFC-supercritical fluid chromatography

Intermediate 1

Preparation of 3-methoxy-2-(2,4,6-trimethylphenyl)-cyclopent-2-en-1-one (previously described as Example 1 step 1 on pages 54-55 of WO 2010/000773 A1)

(19) To a suspension of 2-bromo-3-methoxy-cyclopent-2-en-1-one (6.75 g, 35.3 mmol), 2,4,6-trimethylphenyl boronic acid (6.99 g, 42.6 mmol) and freshly ground potassium phosphate (15 g, 70.6 mmol) in degassed toluene (180 ml) under nitrogen are added Pd(OAc).sub.2 (159 mg, 0.71 mmol) and S-Phos (2-(dicyclohexylphosphino)-2,6-dimethoxybiphenyl) (579 mg, 1.41 mmol), and the reaction heated to 90 C. with stirring under nitrogen for 4 hours. The reaction mixture is partitioned between ethyl acetate (150 ml) and water (150 ml), and the organic layer is removed, silica gel is added to the organic layer, the solvent is evaporated under reduced pressure and the residue is purified by flash chromatography on silica gel to give 3-methoxy-2-(2,4,6-trimethylphenyl)-cyclopent-2-en-1-one (6.2 g).

Intermediate 2

Synthesis of 5-(2-aminoethyl)-3-methoxy-2-(2,4,6-trimethylphenyl)cyclopent-2-en-1-one

(20) Step One: Synthesis of 2-nitroethyl trifluoromethanesulfonate

(21) To a stirred solution of 2-nitroethanol (4.88 ml, 68 mmol) in dichloromethane (200 ml) at 0 C. was added pyridine (11 ml, 136 mmol) followed by dropwise addition of trifluoromethanesulfonic anhydride. The colour of the reaction transitioned from pale pink through dark red to yellow during the addition of the anhydride. The reaction was allowed to warm to room temperature over three hours and then quenched by cautious addition of H.sub.2O (200 ml). The phases were separated and the aqueous phase was extracted with further dichloromethane (2100 ml). The combined organics were washed with saturated aqueous NH.sub.4Cl solution (100 ml) and H.sub.2O (100 ml), dried over MgSO.sub.4, filtered and evaporated to dryness under reduced pressure to give the desired product (4.2 g, 28%) as a yellow/brown oil with was used in subsequent steps without additional purification. .sup.1H NMR (400 MHz, CDCl.sub.3) .sub.H 5.00 (t, 2H), 4.75 (t, 2H). .sup.19F NMR (375 MHz, CDCl.sub.3) .sub.F74.1

(22) Step Two: Synthesis of 3-methoxy-5-(2-nitroethyl)-2-(2,4,6-trimethylphenyl)cyclopent-2-en-1-one

(23) To a stirred solution of 3-methoxy-2-(2,4,6-trimethylphenyl)cyclopent-2-en-1-one (2.30 g, 10.0 mmol) (e.g. preparable by the method shown in Intermediate 1 herein, or preparable by method(s) disclosed in WO 2010/069834 A1 and/or WO 2011/073060 A2) in tetrahydrofuran (100 ml) at 78 C. under an atmosphere of N.sub.2 was added dropwise lithium diisopropylamide (6.11 ml of a 1.8M solution in tetrahydrofuran/ethylbenzene/heptane, 11.0 mmol). The reaction was stirred at 78 C. for 105 minutes and then a solution of 2-nitroethyl trifluoromethanesulfonate (2.68 g, 12.0 mmol) in tetrahydrofuran (10 ml) was added dropwise. The reaction was stirred at 78 C. for 30 minutes and then allowed to warm to room temperature. The reaction was quenched cautiously with H.sub.2O (200 ml) and extracted with EtOAc (3100 ml). The combined organic extracts were washed with brine (50 ml), dried over MgSO.sub.4, filtered and evaporated to dryness under reduced pressure to give a brown oil. The crude product was purified by silica gel chromatography using a 100% hexane to 100% EtOAc gradient to give the desired compound (780 mg, 26%) as a colourless oil.

(24) .sup.1H NMR (400 MHz, CDCl.sub.3) 6.85 (s, 2H), 4.65 (t, 2H), 3.70 (s, 3H), 3.05 (dd, 1H), 2.75-2.65 (m, 1H) 2.55-2.40 (m, 2H), 2.30 (s, 3H), 2.30 (m, 1H), 2.05 (s, 6H).

Step Three: Synthesis of 5-(2-aminoethyl)-3-methoxy-2-(2,4,6-trimethylphenyl)cyclopent-2-en-1-one

(25) To a stirred solution of 3-methoxy-5-(2-nitroethyl)-2-(2,4,6-trimethylphenyl)cyclopent-2-en-1-one (108 mg, 0.356 mmol) in MeOH (10 ml) under an N.sub.2 atmosphere was added ammonium formate (67 mg, 1.07 mmol) followed by 10% Pd/C (5 mg, catalytic). The reaction was heated at reflux for 1 hour, allowed to cool to room temperature and then filtered through a pad of celite, washing through with further MeOH (10 ml). The solvent was removed under reduced pressure to give the crude product (64 mg) which was used without further purification.

(26) .sup.1H NMR (400 MHz, CDCl.sub.3) 6.85 (s, 2H), 3.70 (s, 3H), 2.95 (dd, 1H), 2.90-2.75 (m, 2H), 2.75-2.65 (m, 1H), 2.50 (d, 1H), 2.25 (s, 3H), 2.10-2.05 (m, 1H), 2.05 (2s, 23H), 1.65-1.55 (m, 1H).

Intermediate 2

Alternative synthesis of 5-(2-aminoethyl)-3-methoxy-2-(2,4,6-trimethylphenyl)cyclopent-2-en-1-one

Step One: Synthesis of 1-nitroethylene

(27) To a flask equipped with distillation apparatus was added nitroethanol (60.0 g, 0.44 mol) and phthalic anhydride (146.38 g, 0.66 mol). The flask was evacuated to 110 mmbar and the receiver flask cooled with dry ice and acetone. The mixture was then heated to 130 C. After 1 hr at 130 C. the temperature was slowly increased to 180 C. over 2 hrs. Once the distillation was complete the heating was removed and the distillate was dissolved in 100 mL of anhydrous tetrahydrofuran, dried over anhydrous CaCl.sub.2 and stored as a solution in tetrahydrofuran (33.34 g, 69%).

(28) .sup.1H NMR (400 MHz, CDCl.sub.3) 6.85-6.95 (br, 1H), 6.25-6.35 (br, 1H), 5.60-5.70 (br s, 1H).

Step two: Synthesis of 3-methoxy-5-(2-nitroethyl)-2-(2,4,6-trimethylphenyl)cyclopent-2-en-1-one

(29) To a solution of 3-methoxy-2-(2,4,6-trimethylphenyl)cyclopent-2-en-1-one (2.50 g, 10.86 mmol) in anhydrous tetrahydrofuran (25 mL) at 78 C. under an argon atmosphere was added dropwise lithium diisopropylamide (1.8M in tetrahydrofuran, 6.03 mL, 10.86 mmol) keeping the temperature below 50 C. Once the addition was complete the mixture was allowed to stir for 30 mins. A solution of the nitroethylene (2.38 mL, 10.86 mmol) in THF was then added dropwise over 1 hr using a dropping funnel. Once the addition was complete the mixture was stirred for 30 mins before being allowed to warm to room temperature. After stirring for 1 hr the reaction was quenched by the addition of water (50 mL) followed by saturated ammonium chloride solution (50 mL). The mixture was then extracted with ethyl acetate (320 mL). The combined organic extracts were dried, filtered and evaporated to dryness. The crude product was purified by silica gel chromatography using a hexane/ethyl acetate gradient to give the desired product (2.00 g, 60%) as a colourless oil. .sup.1H NMR (400 MHz, CDCl.sub.3) 6.85 (s, 2H), 4.65 (t, 2H), 3.70 (s, 3H), 3.05 (dd, 1H), 2.75-2.65 (m, 1H) 2.55-2.40 (m, 2H), 2.30 (s, 3H), 2.30 (m, 1H), 2.05 (s, 6H).

Step Three: Synthesis of 5-(2-aminoethyl)-3-methoxy-2-(2,4,6-trimethylphenyl)cyclopent-2-en-1-one

(30) To a solution of 3-methoxy-5-(2-nitroethyl)-2-(2,4,6-trimethylphenyl)cyclopent-2-en-1-one (2.00 g, 6.59 mmol) in MeOH (40.0 mL) was added ammonium formate (2.08 g, 32.96 mmol) followed by palladium on carbon (10%, 0.50 g). The mixture was then stirred for two hours and then filtered through a pad of celite and the filtrate was evaporated to dryness under reduced pressure. The residue was then dissolved in dichloromethane (20 mL) and washed with saturated sodium bicarbonate solution (210 mL). The organic phase was dried over magnesium sulphate, filtered and evaporated to dryness under reduced pressure to give the crude product (0.35 g, 19%) as a brown oil which was used without further purification. .sup.1H NMR (400 MHz, d4-methanol) 6.86-6.89 (s, 2H), 4.64-4.70 (t, 2H), 3.71-3.73 (s, 3H), 3.00-3.08 (m, 1H), 2.66-2.75 (m, 1H), 2.39-2.52 (m, 2H), 2.24-2.32 (m, 4H), 2.06-2.09 (d, 6H).

Intermediate 3

Preparation of 2-(4-Bromo-2,6-dimethyl-phenyl)-3-methoxy-cyclopent-2-en-1-one

Step 1: Preparation of ([4-bromo-2,6-dimethylphenyl]furan-2-yl)methanol (previously described in Example 1 step 1 on pages 51-52 of WO 2010/089210 A1)

(31) 4-Bromo-2,6-dimethyl-1-iodobenzene (5 g, 16 mmol) is dissolved in dry tetrahydrofuran (20 ml) and cooled to 78 C. under an atmosphere of dry nitrogen. Isopropylmagnesium chloride (2M solution in tetrahydrofuran, 10 ml, 20 mmol) is added dropwise with vigorous stirring over 30 minutes. When the addition is complete, the reaction is allowed to warm to room temperature and is stirred for 30 minutes at room temperature. The reaction mixture is cooled to 78 C. and a solution of 2-furaldehyde (2.4 g, 25 mmol) in dry tetrahydrofuran (10 ml) is added dropwise over 30 minutes. Once the addition is complete, the mixture is allowed to warm to room temperature and stirring was continued for 2 h. A solution of saturated aqueous ammonium chloride (30 ml) is added, and the mixture is extracted with dichloromethane (325 ml). The organic extracts are combined, washed with brine, dried over anhydrous magnesium sulfate, filtered and the filtrate is evaporated under reduced pressure. The residue is purified by chromatography on silica gel to give ([4-bromo-2,6-dimethylphenyl]furan-2-yl)methanol (3.71 g).

Step 2: Preparation of 5-(4-bromo-2,6-dimethylphenyl)-4-hydroxycyclopent-2-enone (previously described in Example 1 step 2 on page 52 of WO 2010/089210 A1)

(32) Polyphosphoric acid (500 mg) is added to a warm (55 C.) solution of ([4-bromo-2,6-dimethylphenyl]furan-2-yl)methanol (843 mg, 3 mmol) in acetone (8 ml) and water (2 ml) and the mixture is heated at 55 C. for 24 hours. The mixture is cooled to room temperature and the acetone is removed under reduced pressure. The remaining mixture is partitioned between diethyl ether (20 ml) and water (20 ml). The aqueous phase is extracted with ether (250 ml), and then the organic phases are combined, washed with saturated aqueous sodium bicarbonate solution (20 ml), and brine (20 ml), dried over anhydrous magnesium sulfate, filtered and the filtrate is evaporated under reduced pressure. The residue is purified by chromatography on silica gel to give 5-(4-bromo-2,6-dimethylphenyl)-4-hydroxycyclopent-2-enone (596 mg).

Step 3: Preparation of 2-(4-bromo-2,6-dimethylphenyl)cyclopent-4-ene-1,3-dione (previously described in Example 1 step 3 on page 52 of WO 2010/089210 A1)

(33) To a solution of 5-(4-bromo-2,6-dimethylphenyl)-4-hydroxycyclopent-2-enone (18.33 g. 65 mmol) in acetone (200 ml) at 0 C. is added, dropwise, a solution of Jones reagent (1.67 M, 39 ml, 65 mmol) and the resulting yellow solution is stirred at 0 C. for 90 minutes. The reaction is quenched by the addition of propan-2-ol (1 ml) and stirred for a further 2 hours. Brine (300 ml) is added and the reaction is extracted with ethyl acetate (3250 ml). The organic extracts are combined, washed with brine, dried over anhydrous magnesium sulfate, filtered and the filtrate is concentrated under reduced pressure. The residue is purified by chromatography on silica gel to give 2-(4-bromo-2,6-dimethylphenyl)cyclopent-4-ene-1,3-dione (17.2 g).

Step 4: Preparation of 2-(4-Bromo-2,6-dimethylphenyl)cyclopentane-1,3-dione

(34) To a solution of 2-(4-bromo-2,6-dimethylphenyl)cyclopent-4-ene-1,3-dione (50 g, 0.18 mol) in acetic acid (2000 ml) at 25-30 C. is added zinc powder (82.3 g, 1.26 mol). The resulting suspension is heated to 90 C. for 2 hours, followed by cooling to room temperature then filtration through a bed of diatomaceous earth. The residue is washed with methanol (100 ml2) and the solution is concentrated in vacuo. Distilled water is added and the crude product is extracted with ethyl acetate (500 ml3). Organic fractions are combined then washed with distilled water, brine, then dried over sodium sulfate, filtered and the filtrate is concentrated in vacuo to afford 2-(4-bromo-2,6-dimethylphenyl)cyclopentane-1,3-dione. This material is used directly in the next step without further purification.

Step 5: Preparation of 2-(4-Bromo-2,6-dimethyl-phenyl)-3-methoxy-cyclopent-2-en-1-one

(35) To a solution of 2-(4-bromo-2,6-dimethylphenyl)cyclopentane-1,3-dione (40 g, 0.143 mol) in acetone (2000 ml) is added anhydrous potassium carbonate (98.5 g, 0.714 mol) and iodomethane (45 ml, 0.72 mol). The resulting mixture is stirred at 25-30 C. for 16 hours, then volatile solvents are removed in vacuo, and the residue is diluted with distilled water (200 ml) and extracted with ethyl acetate (3500 ml). Organic fractions are combined, washed with distilled water, brine, then dried over sodium sulphate, filtered and the filtrate concentrated in vacuo. The crude product is purified by silica gel chromatography to afford 2-(4-bromo-2,6-dimethyl-phenyl)-3-methoxy-cyclopent-2-en-1-one.

Example 1

Synthesis of N-[2-[2,4-dioxo-3-(2,4,6-trimethylphenyl)cyclopentyl]ethylcarbamoyl]pyridine-2-carboxamide (Compound A1)

(36) To a solution of the pyridine-2-carboxamide (1.0 mmol, 0.12 g) in tetrahydrofuran (10 mL) was added the oxalyl chloride (1.1 mmol, 0.093 mL, 0.14 g). The mixture was heated in the microwave at 120 C. for 5 min. The 5-(2-aminoethyl)-3-methoxy-2-(2,4,6-trimethylphenyl)cyclopent-2-en-1-one (1.0 mmol, 0.27 g) was then added and the mixture heated for a further 5 min at 120 C., then Hunigs base (0.5 mL) was added. After stirring 1 h, the reaction was reduced in vacuo and purified by silica gel chromatography to afford N-[2-[4-methoxy-2-oxo-3-(2,4,6-trimethylphenyl)cyclopent-3-en-1-yl]ethylcarbamoyl]pyridine-2-carboxamide (0.17 mmol, 0.070 g).

(37) The above material was dissolved in ethanol (2 mL) and 1M hydrochloric acid (2 mL) and the mixture heated to 60 C. for 4 h. The ethanol was removed in vacuo, the pH of the aqueous adjusted to 5 using saturated aqueous NaHCO.sub.3 and the aqueous layer was extracted with chloroform. The combined organic layers were dried, filtered and reduced in vacuo to give N-[2-[4-hydroxy-2-oxo-3-(2,4,6-trimethylphenyl)cyclopent-3-en-1-yl]ethylcarbamoyl]pyridine-2-carboxamide (0.046 g, 0.11 mmol). 1H NMR (400 MHz, d4-methanol) 1.68-1.78 (1H, m), 2.03-2.08 (6H, s), 2.13-2.21 (1H, m), 2.22-2.26 (3H, s), 2.44-2.52 (1H, dd), 2.77-2.84 (1H, m), 2.88-2.97 (1H, dd) 3.48-3.54 (1H, dt), 6.83-6.87 (2H, s), 7.59-7.64 (1H, m), 7.97-8.03 (1H, dt), 8.16-8.22 (1H, d), 8.64-8.68 (1H, d).

Example 2

Synthesis of Compound A40

Step One: Synthesis of 2-[2-methoxy-4-oxo-3-(2,4,6-trimethylphenyl)cyclopent-2-en-1-yl]acetonitrile

(38) To a solution of 3-methoxy-2-(2,4,6-trimethylphenyl)cyclopent-2-en-1-one (intermediate 1, 43.420 mmol, 10.0 g) in THF (100 mL), under nitrogen at 78 C., LiHMDS (1M in THF, 47.762 mL, 47.762 mmol) was added dropwise. The temperature of the reaction was maintained below 55 C. during the dropwise addition of LiHMDS. After stirring for 15 minutes at 78 C., 2-bromoacetonitrile (52.1 mmol, 6.25 g, 3.63 mL) in THF (20 mL) was added over a period of 15 minutes. Stirring was continued at 78 C. for 40 minutes then the reaction was warmed to room temperature. After quenching the reaction with saturated ammonium chloride the solvent was removed under reduced pressure and the crude material was dissolved in dichloromethane and water. The phases were separated and the aqueous layer was extracted with dichloromethane. The combined organic layers were washed with water and brine then dried over MgSO.sub.4 and the solvent was removed under reduced pressure to leave a brown oil. The crude material was purified by silica gel chromoatography (gradient elution: 0-100% ethyl acetate in hexane) to give the desired product (11.136 g, 95%) as a brown oil. .sup.1H NMR (400 MHz, CDCl.sub.3) 6.88 (d, 2H), 3.57 (s, 3H), 3.14-3.32 (m, 1H), 2.88 (dd, 1H), 2.75-2.82 (m, 2H), 2.48 (dd, 1H), 2.23-2.34 (m, 3H), 2.14-2.22 (m, 3H), 2.06-2.14 (m, 3H).

Step Two: Synthesis of tert-butyl N-[2-[2-methoxy-4-oxo-3-(2,4,6-trimethylphenyl)cyclopent-2-en-1-yl]ethyl]carbamate

(39) To a solution of 2-[2-methoxy-4-oxo-3-(2,4,6-trimethylphenyl)cyclopent-2-en-1-yl]acetonitrile (3.713 mmol, 1.00 g) in methanol (28 mL) under nitrogen was added tert-butoxycarbonyl tert-butyl carbonate (7.43 mmol, 1.62 g) and nickel (II) chloride (0.668 mmol, 0.0867 g). The mixture was cooled to 5 C. in an acetone/dry ice bath before the sodium borohydride (22.28 mmol, 0.8601 g) was added portionwise over 30 minutes. After stirring for 1 hour at 5 C. the reaction was allowed to warm to room temperature then stirred for a further 3.5 hours. N-(2-aminoethyl)ethane-1,2-diamine (3.713 mmol, 0.3909 g, 0.409 mL) was added and the mixture left to stir at room temperature for 1 hour. After diluting with saturated sodium bicarbonate and ethyl acetate, the phases were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with water and brine then dried over MgSO.sub.4 and the solvent was removed under reduced pressure to leave a brown oil. The crude material was purified by silica gel chromoatography (gradient elution: 0-75% ethyl acetate in hexane) to give the desired product (1.167 g, 84%) as a colourless oil. .sup.1H NMR (400 MHz, CDCl.sub.3) 6.78-6.95 (m, 2H), 4.60 (br. s., 1H), 3.44-3.63 (m, 3H), 3.14-3.36 (m, 2H), 2.86-3.04 (m, 1H), 2.68-2.85 (m, 1H), 2.22-2.37 (m, 4H), 2.01-2.16 (m, 6H), 1.36-1.71 (m, 10H).

Step Three: Synthesis of 2-[2,4-dioxo-3-(2,4,6-trimethylphenyl)cyclopentyl]ethylammonium chloride

(40) To a solution of tert-butyl N-[2-[4-methoxy-2-oxo-3-(2,4,6-trimethylphenyl)cyclopent-3-en-1-yl]ethyl]carbamate (2.14 mmol, 0.800 g) in acetone (30 mL) was added Hydrochloric acid (2M, 40 mmol, 20 mL). The mixture was heated to 70 C. for 3 h and then the mixture was concentrated in vacuo to give the desired product as a a white solid. 1H NMR (400 MHz, DMSO-d6) 1.54-1.78 (m, 1H) 1.80-2.12 (m, 8H) 2.16-2.42 (m, 5H) 2.67 (br. s., 1H) 2.76-3.01 (m, 3H) 6.83 (s, 2H) 7.91 (br. s., 3H)

Step Four: Synthesis of N-[2-[2,4-dioxo-3-(2,4,6-trimethylphenyl)cyclopentyl]ethyl]-5,5-dimethyl-4H-isoxazole-3-carboxamide

(41) The 4-(2-aminoethyl)-2-(2,4,6-trimethylphenyl)cyclopentane-1,3-dione hydrochloride (0.541 mmol, 0.160 g) was suspended in dichloromethane (10 mL) then (2,3,4,5,6-pentafluorophenyl) 5,5-dimethyl-4H-isoxazole-3-carboxylate (0.595 mmol, 0.184 g) was added followed by the N,N-diethylethanamine (1.62 mmol, 0.164 g, 0.226 mL). After stirring for 1.5 h, the reaction mixture was acidified with 2M HCl and the organic layer was concentratd in vacuo and the crude product was purified by silica gel chromatography (gradient elution: 0-100% ethyl acetate in hexane) to give the desired product as colourless oil (0.186 g). 1H NMR (400 MHz, CDCl.sub.3) =7.43-7.29 (m, 1H), 6.82 (s, 2H), 3.63-3.22 (m, 2H), 2.93 (s, 2H), 2.82-2.59 (m, 2H), 2.29-2.11 (m, 4H), 2.10-1.63 (m, 8H), 1.43 (d, 6H)

Example 3

Synthesis of Compound A43

Step One: Synthesis of 2-[4-(4-chloropyrazol-1-yl)-2,6-dimethyl-phenyl]-3-methoxy-cyclopent-2-en-1-one

(42) A flask charged with 2-(4-bromo-2,6-dimethyl-phenyl)-3-methoxy-cyclopent-2-en-1-one (2 g, 6.7755 mmol), 4-chloro-1H-pyrazole (1.39 g, 13.551 mmol), potassium carbonate (2.83 g, 20.3265 mmol) and copper (I) Iodide (0.658 g, 3.3878 mmol) was evacuated and purged with nitrogen. Chlorobenzene (10 mL) was added, followed by N,N-dimethylethylene diamine (0.737 mL, 6.775 mmol), and the reaction was refluxed (131 C.) for 1 hour. The reaction was allowed to cool to ambient temperature, diluted with chloroform (25 mL) and washed with saturated aqueous ammonium chloride (25 mL). The aqueous layer was acidified to pH 5 with 2N HCl and re-extracted with chloroform. The combined organic layers were filtered through a PTFE frit, concentrated in vacuo and diluted with acetone (10 mL). Potassium carbonate (1.89 g, 13.55 mmol) and iodomethane (0.844 mL, 13.55 mmol) were added to the above solution, and the reaction was stirred for 4 hours at ambient temperature. The reaction was diluted with chloroform (25 mL), washed with saturated aqueous ammonium chloride (25 mL) and filtered through a PTFE frit. The filtrate was dry loaded onto silica, purified by silica gel chromatography (gradient elution: 20-100% EtOAc in hexane) to give 2-[4-(4-chloropyrazol-1-yl)-2,6-dimethyl-phenyl]-3-methoxy-cyclopent-2-en-1-one (1.61 g, 5.08 mmol, 75.0% Yield) as a white solid. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.87 (s, 1H), 7.61 (s, 1H), 7.34 (s, 2H), 3.78 (s, 3H), 2.93-2.79 (m, 2H), 2.73-2.61 (m, 2H), 2.20 (s, 6H).

Step Two: Synthesis of 2-[3-[4-(4-chloropyrazol-1-yl)-2,6-dimethyl-phenyl]-2-methoxy-4-oxo-cyclopent-2-en-1-yl]acetonitrile

(43) An oven-dried 3-neck flask was charged with 2-[4-(4-chloropyrazol-1-yl)-2,6-dimethyl-phenyl]-3-methoxy-cyclopent-2-en-1-one (869 mg, 2.74 mmol), purged with nitrogen, and THF (8.69 mL) was added. The reaction is cooled to 65 C. and LiHMDS (1M in THF, 3.01 mL, 3.01 mmol) was added dropwise over a period of 2 minutes and the reaction was allowed to stir for 20 minutes. A solution of 2-bromoacetonitrile (395 mg, 3.2918 mmol) in THF (1.738 mL) was then added dropwise, and the reaction was allowed to stir for a further 60 minutes, before being allowed to warm to ambient temperature over a period of 40 minutes. The reaction was quenched by the addition of saturated aqueous ammonium chloride solution (25 ml) and the reaction was allowed to stir for a further 10 minutes. The reaction was extracted with EtOAc (225 mL). The combined organic layers were filtered through a PTFE frit, dry loaded onto silica and purified by silica gel chromatography (0-100% EtOAc in hexane) to give 2-[3-[4-(4-chloropyrazol-1-yl)-2,6-dimethyl-phenyl]-4-methoxy-2-oxo-cyclopent-3-en-1-yl]acetonitrile (854 mg, 2.40 mmol, 87.5% yield) as a beige solid. .sup.1H NMR (400 MHz, CDCl.sub.3) 2.21 (s, 3H), 2.30 (s, 3H), 2.52 (dd, 1H), 2.76-2.95 (m, 3H), 3.28 (dd, 1H), 3.60 (s, 3H), 7.36 (s, 2H), 7.62 (s, 1H), 7.89 (s, 1H).

Step Three: Synthesis of tert-butyl N-[2-[3-[4-(4-chloropyrazol-1-yl)-2,6-dimethyl-phenyl]-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl]carbamate

(44) Prepared from 2-[3-[4-(4-chloropyrazol-1-yl)-2,6-dimethyl-phenyl]-2-methoxy-4-oxo-cyclopent-2-en-1-yl]acetonitrile according to substantially the same procedure used to prepare A44 (step 2) to give the desired product (194 mg, 30%) as a pale yellow gum. .sup.1H NMR (500 MHz, CDCl.sub.3 and a few drops of d4-methanol) 7.88 (m, 1H), 7.62 (s, 1H), 7.34 (s, 2H), 4.59-4.75 (m, 1H), 3.57 (s, 5H), 3.03-3.19 (m, 1H), 2.65-2.80 (m, 1H), 2.33-2.48 (m, 1H), 2.22 (d, 6H), 1.45 (s, 10H).

Step Four: Synthesis of 2-[3-[4-(4-chloropyrazol-1-yl)-2,6-dimethyl-phenyl]-2,4-dioxo-cyclopentyl]ethylammonium chloride

(45) To a solution of tert-butyl N-[2-[3-[4-(4-chloropyrazol-1-yl)-2,6-dimethyl-phenyl]-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl]carbamate (0.100 g, 0.224 mmol) in acetone (2 mL) was added 2M HCl (2 mL). The reaction mixture was heated to 120 C. under microwave irradiation for 20 minutes after which it was diluted with dichloromethane and the phases were separated. The aqueous phase was evaporated to dryness to give the desired product (0.085 g, 99%) as an off white glass. .sup.1H NMR (500 MHz, D.sub.2O) 7.89 (s, 1H), 7.58 (s, 1H), 7.09 (m, 2H), 3.11 (m, 2H), 3.00 (m, 1H), 2.88 (m, 1H), 2.50 (m, 1H), 2.11 (m, 1H), 1.99 (s, 6H), 1.86 (m, 1H).

(46) Note: The above-shown HCl salt of the amine (RNH.sub.3.sup.+Cl.sup.), produced in the above process, can be converted to the corresponding free amine (RNH.sub.2) if desired, e.g. via an ion exchange column.

Step Five: Synthesis of of Compound A43

(47) The 2-[3-[4-(4-chloropyrazol-1-yl)-2,6-dimethyl-phenyl]-2,4-dioxo-cyclopentyl]ethylammonium chloride (0.523 mmol, 0.200 g) was suspended in dichloromethane (10 mL) then the (2,3,4,5,6-pentafluorophenyl) 5,5-dimethyl-4H-isoxazole-3-carboxylate (0.575 mmol, 0.178 g) was added followed by the N,N-diethylethanamine (1.57 mmol, 0.159 g, 0.219 mL). On stirring at room temperature the solid all gradually dissolved. After stirring for 2 hours, the reaction mixture was washed with 2M HCl, the organic layer was concentrated in vacuo and purified by silica gel chromatography (gradient elution: 0-100% ethyl acetate in hexane) to give the desired product as a white foam (0.190 g). 1H NMR (400 MHz, CDCl.sub.3) =7.83 (s, 1H), 7.57 (s, 1H), 7.46-7.33 (m, 1H), 7.22 (s, 2H), 3.41 (s, 2H), 2.96 (s, 2H), 2.90-2.68 (m, 2H), 2.33-2.20 (m, 1H), 2.16-1.88 (m, 7H), 1.87-1.67 (m, 1H), 1.44 (s, 6H)

Example 4

Synthesis of Compound A36

Step One: Synthesis of 2-[2-methoxy-4-oxo-3-(2,4,6-trimethylphenyl)cyclopent-2-en-1-yl]ethylammonium chloride

(48) To a solution of tert-butyl N-[2-[2-methoxy-4-oxo-3-(2,4,6-trimethylphenyl)cyclopent-2-en-1-yl]ethyl]carbamate (15.06 mmol, 5.624 g) in dichloromethane (30 mL) at room temperature was added hydrogen chloride (4M in 1,4-dioxane, 40 mmol, 10 mL). After stirring at room temperature for 4 hours the solvent was removed to leave an off white solid which was carried on directly to the next stage of the synthesis.

Step Two: Synthesis of 4-[2-[[3-chloro-5-(trifluoromethyl)-2-pyridyl]amino]ethyl]-3-methoxy-2-(2,4,6-trimethylphenyl)cyclopent-2-en-1-one

(49) 2-[2-methoxy-4-oxo-3-(2,4,6-trimethylphenyl)cyclopent-2-en-1-yl]ethylammonium chloride (0.100 g, 0.323 mmol), 3-chloro-2-fluoro-5-(trifluoromethyl)pyridine (0.323 mmol) and potassium carbonate (0.403 mmol) were suspended in acetonitrile (3 mL) and the reaction mixture was heated at reflux for 5 hours. After cooling the reaction to room temperature, the mixture was diluted with 2M HCl to pH 7 and extracted with EtOAc. The organic phase was dried and concentrated in vacuo and purified by silica gel chromatography (gradient elution: 5% EtOAc in iso-hexane to 100% EtOAc) to give the desired product as a gum (0.056 g, 0.12 mmol). 1H NMR (400 MHz, CDCl.sub.3) 8.29 (d, 1H), 7.66-7.62 (m, 1H), 6.86 (s, 2H), 5.49 (t, 1H), 3.73-3.63 (m, 2H), 3.57-3.45 (m, 3H), 2.99 (dddd, 1H), 2.81 (dd, 1H), 2.39 (dd, 1H), 2.28-2.21 (m, 4H), 2.15-2.08 (m, 6H), 1.84-1.68 (m, 1H)

Step Three: Synthesis of Compound A36

(50) 4-[2-[[3-chloro-5-(trifluoromethyl)-2-pyridyl]amino]ethyl]-3-methoxy-2-(2,4,6-trimethylphenyl)cyclopent-2-en-1-one (0.056 g, 0.12 mmol) was dissolved in acetone (5.89 mL/mmol) and hydrochloric acid (2M) (5.89 mL/mmol, 1.5 mmol) was added.

(51) The reaction mixture was heated to 60 C. and allowed to stir for 5.5 hours. The mixture was coiled down, concentrated in vacuo to remove the acetone and the resulting aqueous layer was neutralized to pH 7 by the addition of aqueous potassium hydroxide. The aqueous layer was extracted with EtOAc and the organic layers were dried and concentrated in vacuo to to give the desired product as a white glassy solid (0.0505 g, 0.115 mmol). 1H NMR (400 MHz, d4-methanol) 8.33-8.23 (m, 1H), 8.20-8.08 (m, 1H), 6.88 (s, 2H), 3.86-3.77 (m, 1H), 3.74-3.67 (m, 1H), 3.02 (dd, 1H), 2.90-2.79 (m, 1H), 2.56-2.43 (m, 1H), 2.26 (s, 3H), 2.15 (qd, 1H), 2.09-2.03 (m, 6H), 2.00-1.89 (m, 1H)

Example 5

Synthesis of Compound A9

Step One: Syntheis of phenyl N-[2-[2-methoxy-4-oxo-3-(2,4,6-trimethylphenyl)cyclopent-2-en-1-yl]ethyl]carbamate

(52) 2-[2-methoxy-4-oxo-3-(2,4,6-trimethylphenyl)cyclopent-2-en-1-yl]ethylammonium chloride (2.724 mmoll) was taken up into dichloromethane (15 mL). Pyridine (3.541 mmol) was added followed by addition of phenyl chloroformate (3.269 mmol). The reaction mixture was stirred for 2 hours then a further 0.5 eq of phenyl chloroformate was added. After stirring for 1 hour, a further 1 eq of pyridine was added and stirring continued for 1 hour. The reaction mixture was left to stand over night. The reaction mixture was diluted with DCM and then quenched with water. The reaction mixture was extracted with DCM and the organic layers were dried with MgSO.sub.4, concentrated in vacuo and purified by silica gel chromatography (gradient elution: 5% EtOAc in iso-hexane to 100% EtOAc) to give the desire product as a yellow gum (0.485 g, 1.23 mmol). 1H NMR (400 MHz, CDCl.sub.3) 7.40-7.32 (m, 2H), 7.24-7.17 (m, 1H), 7.13 (d, 2H), 6.86 (s, 2H), 5.14 (br. s., 1H), 3.58-3.50 (m, 3H), 3.42 (q, 2H), 2.99 (br. s., 1H), 2.81 (dd, 1H), 2.32 (dd, 1H), 2.28-2.22 (m, 3H), 2.23-2.16 (m, 1H), 2.11 (s, 6H), 1.80-1.68 (m, 1H)

Step Two: Synthesis of 1-[2-[2-methoxy-4-oxo-3-(2,4,6-trimethylphenyl)cyclopent-2-en-1-yl]ethyl]-3-phenyl-urea

(53) Phenyl N-[2-[2-methoxy-4-oxo-3-(2,4,6-trimethylphenyl)cyclopent-2-en-1-yl]ethyl]carbamate (0.4025 mmol) was taken up into acetonitrile (2 mL) and placed in a microwave vial. N,N-diethylethanamine (0.4025 mmol) was added followed by aniline (0.8050 mmol). The reaction mixture was heated at 86 C. for 90 min. The reaction mixture was diluted with EtOAc and washed with 2M HCl. The aqueous layer was extracted with EtOAc, the organic layers were concentrated invacuo and purified by silica gel chromatography (gradient elution: 5% EtOAc in iso-hexane to 100% EtOAc) to give the desired product (0.0677 g, 0.172 mmol). 1H NMR (400 MHz, CDCl.sub.3) 7.31-7.21 (m, 4H), 7.09-7.00 (m, 1H), 6.91 (s, 1H), 6.85 (s, 2H), 5.25 (t, 1H), 3.52-3.46 (m, 2H), 3.36-3.25 (m, 1H), 2.95-2.86 (m, 1H), 2.77 (dd, 1H), 2.30 (dd, 1H), 2.25 (s, 2H), 2.18-2.11 (m, 1H), 2.08 (d, 4H), 1.54 (tdd, 1H)

Step Three: Synthesis of 1-[2-[2,4-dioxo-3-(2,4,6-trimethylphenyl)cyclopentyl]ethyl]-3-phenyl-urea

(54) 1-[2-[2-methoxy-4-oxo-3-(2,4,6-trimethylphenyl)cyclopent-2-en-1-yl]ethyl]-3-phenyl-urea (0.086 g, 0.22 mmol) was dissolved in acetone (5.89 mL/mmol) and hydrochloric acid (2M, 5.89 mL/mmol, 2.6 mmol) was added. The reaction mixture was heated to 60 C. for 8 hours. The reaction mixture was allowed to cool over the weekend during which time a pale solid crashed out of solution. This solid was collected by filtration and washed with water, dried to give the desired product as a white powder (0.0544 g, 0.144 mmol). 1H NMR (400 MHz, d.sub.4-methanol) =7.38-7.31 (m, 2H), 7.27-7.18 (m, 2H), 7.00-6.92 (m, 1H), 6.86 (s, 2H), 3.42-3.33 (m, 2H), 2.95-2.75 (m, 2H), 2.48-2.41 (m, 1H), 2.25 (s, 3H), 2.12-2.06 (m, 1H), 2.05 (s, 6H), 1.66 (qd, 1H)

Example 6

Synthesis of Compound A73

(55) To a solution of 5-(2-aminoethyl)-3-methoxy-2-(2,4,6-trimethylphenyl)cyclopent-2-en-1-one (0.100 g, 0.366 mmol, 100 mg) in dichloromethane (1 mL) was added Hunig's base (0.402 mmol, 69 L, 52 mg) followed by 4-fluorobenzenesulfonyl chloride (0.366 mmol). The mixture was stirred for 4 h and a further 1 eq of 4-fluorobenzenesulfonyl chloride was added then the mixture was stirred for a further 4 h. The reaction was worked up by dilution with DCM and washing with 2M HCl. The combined organic layer was dried of MgSO.sub.4, filtered and concentrated in vacuo. The resulting residue was purified by preparative HPLC to give the desired sulfonamide, which was dissolved in ethanol (2 mL) and aqueous hydrochloric acid (2M, 2 mL). The reaction mixture was heated to 60 C. for 4 h, cooled to room temperature and then concentrated in vacuo to give the desired product (29.4 mg). 1H NMR (400 MHz, d4-methanol) 8.05 (d, 2H), 7.89 (d, 2H), 6.84 (br. s., 2H), 3.04 (t, 2H), 2.88-2.66 (m, 2H), 2.30 (dd, 1H), 2.23 (s, 3H), 2.07-1.90 (m, 7H), 1.58 (qd, 1H)

Example 7

Preparation of 1-[2-[2,4-dioxo-3-(2,4,6-trimethylphenyl)cyclopentyl]ethyl]-3-[4-(trifluoromethyl)-2-pyridyl]urea (Compound A2)

Step 1: Preparation of phenyl N-[4-(trifluoromethyl)-2-pyridyl]carbamate

(56) To a solution of 4-(trifluoromethyl)pyridin-2-amine (10 g) in dichloromethane (100 mL) was added pyridine (6.49 mL). The solution was cooled with an ice water bath and phenyl chloroformate (9.286 mL) was added drop-wise, taking care to keep the internal reaction temperature below 5 C. Further dichloromethane (20 mL) was added to improve stirring. The reaction mixture was allowed to warm to room temperature and then stirred for 40 minutes. The reaction mixture was partitioned between water and dichloromethane (100 mL), and then extracted with further dichloromethane (100 mL). The organic layers were dried over anhydrous sodium sulfate and concentrated to give phenyl N-[4-(trifluoromethyl)-2-pyridyl]carbamate (18.92 g). .sup.1H NMR (400 MHz, CDCl.sub.3) 9.33 (br s, 1H), 8.55 (d, 1H), 8.37 (s, 1H), 7.45 (m, 2H), 7.22-7.33 (m, 4H)

Step 2: Preparation of 1-[2-[4-methoxy-2-oxo-3-(2,4,6-trimethylphenyl)cyclopent-3-en-1-yl]ethyl]-3-[4-(trifluoromethyl)-2-pyridyl]urea

(57) To a suspension of 5-(2-aminoethyl)-3-methoxy-2-(2,4,6-trimethylphenyl)cyclopent-2-en-1-one hydrochloride (0.100 g) and phenyl N-[4-(trifluoromethyl)-2-pyridyl]carbamate (Intermediate 2, 0.100 g) in dichloromethane (2.5 mL) was added diisopropylethylamine (0.09 mL). The mixture was stirred for 4 hours and then partitioned with 2M hydrochloric acid. The aqueous phase was extracted with further dichloromethane (2). The combined organics were dried with magnesium sulfate, concentrated and purified by chromatography on silica to give 1-[2-]4-methoxy-2-oxo-3-(2,4,6-trimethylphenyl)cyclopent-3-en-1-yl]ethyl]-3-[4-(trifluoromethyl)-2-pyridyl]urea as a white solid (0.066 g). .sup.1H NMR (400 MHz, CDCl.sub.3) 9.28 (brs, 1H) 8.94 (s, 1H) 8.35 (d, 1H) 7.04-7.10 (m, 1H) 6.86 (s, 1H) 3.48-3.59 (m, 5H) 2.95-3.06 (m, 1H) 2.82 (dd, 1H) 2.36-2.43 (m, 1H) 2.25-2.32 (m, 4H) 2.11 (d, 6H) 1.67-1.81 (m, 1H)

Step 3: Preparation of 1-[2-[2,4-dioxo-3-(2,4,6-trimethylphenyl)cyclopentyl]ethyl]-3-[4-(trifluoromethyl)-2-pyridyl]urea

(58) A solution of 1-[2-[4-methoxy-2-oxo-3-(2,4,6-trimethylphenyl)cyclopent-3-en-1-yl]ethyl]-3-[4-(trifluoromethyl)-2-pyridyl]urea (0.052 g) in acetone (0.66 mL) and 2M hydrochloric acid (0.66 mL) was heated to 60 C. for 4 hours. Upon cooling the mixture was concentrated to remove the acetone and the aqueous residue was extracted with ethyl acetate. The solid was suspended in the organic phase so the biphasic solution was filtered and a white solid collected. The organic phase was dried over anhydrous magnesium sulfate and concentrated to give a second white solid. Both solids collected were the desired compound and so were combined and triturated with ether to give 1-[2-[2,4-dioxo-3-(2,4,6-trimethylphenyl)cyclopentyl]ethyl]-3-[4-(trifluoromethyl)-2-pyridyl]urea as a white solid.

(59) .sup.1H NMR (400 MHz, CD.sub.3OD) 8.36-8.47 (m, 1H), 7.60 (s, 1H), 7.42 (d, 1H), 6.88 (s, 2H), 3.47-3.56 (m, 2H), 2.97 (dd, 1H), 2.77-2.89 (m, 1H), 2.50 (dd, 1H), 2.27 (s, 3H), 2.17 (d, 1H), 2.00-2.10 (m, 6H), 1.69-1.82 (m, 1H)

Example 8

Preparation of 1-[2-[2,4-dioxo-3-(2,4,6-trimethylphenyl)cyclopentyl]ethyl]-3-phenyl-thiourea (Compound A90)

Step 1: Preparation of 1-[2-[4-methoxy-2-oxo-3-(2,4,6-trimethylphenyl)cyclopent-3-en-1-yl]ethyl]-3-phenyl-thiourea

(60) To a solution of 5-(2-aminoethyl)-3-methoxy-2-(2,4,6-trimethylphenyl)cyclopent-2-en-1-one (Intermediate 2, 0.100 g) in chloroform (1 mL) was added the phenyl isothiocyanate (0.049 g) and the mixture stirred for 4 hours. The reaction was partitioned between DCM and 2M hydrochloric acid. The organic layer was dried over anhydrous sodium sulfate and concentrated to give crude 1-[2-[4-methoxy-2-oxo-3-(2,4,6-trimethylphenyl)cyclopent-3-en-1-yl]ethyl]-3-phenyl-thiourea.

Step 2: Preparation of 1-[2-[2,4-dioxo-3-(2,4,6-trimethylphenyl)cyclopentyl]ethyl]-3-phenyl-thiourea

(61) The crude 1-[2-[4-methoxy-2-oxo-3-(2,4,6-trimethylphenyl)cyclopent-3-en-1-yl]ethyl]-3-phenyl-thiourea from Step 1 was dissolved in ethanol (2 mL) and 1M hydrochloric acid (2 mL) and the mixture heated to 60 C. for 4 hours. The reaction mixture was concentrated and purified by chromatography on silica to give 1-[2-[2,4-dioxo-3-(2,4,6-trimethylphenyl)cyclopentyl]ethyl]-3-phenyl-thiourea (0.055 g).

(62) .sup.1H NMR (400 MHz, CD.sub.3OD) 7.29-7.42 (m, 3H) 7.14-7.23 (m, 2H) 6.86 (s, 2H) 3.66-3.80 (m, 2H) 2.88-2.99 (m, 1H) 2.70-2.82 (m, 1H) 2.56 (d, 1H) 2.24 (s, 3H) 1.99-2.20 (m, 7H) 1.68-1.81 (m, 1H)

Example 9

Preparation of 4-[2-[(5-bromopyrimidin-2-yl)amino]ethyl]-2-(2,4,6-trimethylphenyl)cyclopentane-1,3-dione (Compound A126)

Step 1: Preparation of 4-[2-[(5-bromopyrimidin-2-yl)amino]ethyl]-2-(2,4,6-trimethylphenyl)cyclopentane-1,3-dione

(63) A flask was charged with 4-(2-aminoethyl)-2-(2,4,6-trimethylphenyl)cyclopentane-1,3-dione hydrochloride (0.250 g, 0.845 mmol) was dissolved in 1,4-dioxane (3 mL) and N,N-diethylethanamine (0.930 mmol) was added. After stirring for 2 mins, cesium carbonate (2.54 mmol), 5-bromo-2-iodo-pyrimidine (0.845 mmol), (5-diphenylphosphanyl-9,9-dimethyl-xanthen-4-yl)-diphenyl-phosphane (0.127 mmol) and tris(dibenzylideneacetone)dipalladium(0) (0.0423 mmol) were added. The reaction mixture was heated at 90 C. for 3.5 hours then cooled to room temperature. The soluction was diluted with 2M HCl and extracted twice with EtOAc. The organic layers were dried (MgSO.sub.4) and concentrated in vacuo to leave an orange oil which was purified by flash column chromatography using a gradient elution from DCM to 10% MeOH in DCM to furnish 4-[2-[(5-bromopyrimidin-2-yl)amino]ethyl]-2-(2,4,6-trimethylphenyl)cyclopentane-1,3-dione (0.074 g, 0.18 mmol, 21% yield).

(64) 1H NMR (400 MHz, CD.sub.3OD) 8.30 (s, 2H), 6.92-6.74 (m, 2H), 3.56-3.43 (m, 2H), 2.95-2.85 (m, 1H), 2.79 (br. s., 1H), 2.46 (dd, 17.7 Hz, 1H), 2.24 (s, 3H), 2.22-2.10 (m, 1H), 2.04 (d, 6H), 1.76-1.63 (m, 1H)

Example 10

Preparation of 1-[2-[2,4-dioxo-3-(2,4,6-trimethylphenyl)cyclopentyl]ethyl]-1-methyl-3-(2-pyridyl)urea (Compound A101)

Step 1: Preparation of tert-butyl N-[2-[4-methoxy-2-oxo-3-(2,4,6-trimethylphenyl)cyclopent-3-en-1-yl]ethyl]-N-methyl-carbamate

(65) tert-Butyl N-[2-[4-methoxy-2-oxo-3-(2,4,6-trimethylphenyl)cyclopent-3-en-1-yl]ethyl]carbamate (0.20600 g, 0.5515 mmol) was dissolved in DMF (8 mL) and iodomethane (0.8273 mmol) and sodium hydride (60% dispersion in mineral oil, 0.8273 mmol) were added. The reaction mixture was stirred at room temperature for 3 hour, then quenched by the addition of saturated sodium bicarbonate solution. The mixture was extracted twice with diethyl-ether and the combined organic layers were washed with water, dried (MgSO.sub.4) and concentrated in vacuo to leave a yellow oil. The resulting residue was purified by flash column chromatography using a gradient elution from 5% EtOAc in i-hexane to 100% EtOAc to furnish tert-butyl N-[2-[4-methoxy-2-oxo-3-(2,4,6-trimethylphenyl)cyclopent-3-en-1-yl]ethyl]-N-methyl-carbamate (0.177 g, 0.457 mmol, 83% yield).

(66) 1H NMR (400 MHz, CDCl.sub.3) 6.91-6.78 (m, 2H), 3.53 (s, 3H), 3.46-3.21 (m, 2H), 2.88 (s, 4H), 2.80-2.68 (m, 1H), 2.31 (s, 1H), 2.30-2.24 (m, 3H), 2.24-2.13 (m, 1H), 2.13-2.07 (m, 6H), 1.55 (s, 1H), 1.47 (s, 9H)

Step 2: Preparation of 1-[2-[4-methoxy-2-oxo-3-(2,4,6-trimethylphenyl)cyclopent-3-en-1-yl]ethyl]-1-methyl-3-(2-pyridypurea

(67) tert-Butyl N-[2-[4-methoxy-2-oxo-3-(2,4,6-trimethylphenyl)cyclopent-3-en-1-yl]ethyl]-N-methyl-carbamate (0.102 g, 0.263 mmol) was stirred for 2 hours at room temperature in hydrogen chloride (4M in 1,4 Dioxane, 2 mL, 8 mmol). The reaction mixture was concentrated in vacuo to leave a yellow gum which was taken up in dichloromethane (2 mL) and phenyl N-(2-pyridyl)carbamate (0.316 mmol) was added followed by N,N-diethylethanamine (0.526 mmol). After stirring at room temperature for 1.5 hours, the reaction mixture was heated at reflux for 2.5 hours. The reaction mixture was cooled to room temperature, diluted with 2M HCl and extracted twice with DCM. The organic layers were dried (MgSO.sub.4) and concentrated in vacuo to leave an orange gum which was purified by flash column chromatography using a gradient elution from 5% EtOAc in i-hexane to 100% EtOAc to furnish 1-[2-[4-methoxy-2-oxo-3-(2,4,6-trimethylphenyl)cyclopent-3-en-1-yl]ethyl]-1-methyl-3-(2-pyridypurea (0.0906 g, 0.222 mmol, 84% yield).

(68) 1H NMR (400 MHz, CDCl.sub.3) 8.19 (d, 1H), 8.06 (d, 1H), 7.68-7.55 (m, 1H), 7.24 (br. s., 1H), 6.99-6.91 (m, 1H), 6.86 (s, 2H), 3.61-3.43 (m, 5H), 3.12-3.03 (m, 3H), 2.94 (br. s., 1H), 2.87-2.76 (m, 1H), 2.33 (dd, 1H), 2.27-2.20 (m, 4H), 2.10 (s, 6H), 1.78-1.64 (m, 1H)

Step 3: Preparation of 1-[2-[2,4-dioxo-3-(2,4,6-trimethylphenyl)cyclopentyl]ethyl]-1-methyl-3-(2-pyridypurea

(69) 1-[2-[4-Methoxy-2-oxo-3-(2,4,6-trimethylphenyl)cyclopent-3-en-1-yl]ethyl]-1-methyl-3-(2-pyridypurea (0.090 g, 0.22 mmol) was dissolved in acetone (5.89 mL/mmol) and hydrochloric acid (2M solution, 5.89 mL/mmol, 2.6 mmol) was added. The reaction mixture was heated to 60 C. for 4 hours. The reaction mixture was concentrated in vacuo to furnish 1-[2-[2,4-dioxo-3-(2,4,6-trimethylphenyl)cyclopentyl]ethyl]-1-methyl-3-(2-pyridypurea (0.0860 g, 0.219 mmol, 99% yield).

(70) 1H NMR (400 MHz, CDCl.sub.3) 8.26 (d, 2H), 7.57 (d, 1H), 7.41 (t, 1H), 6.89 (s, 2H), 3.22-2.98 (m, 5H), 2.83 (d, 1H), 2.48 (d, 1H), 2.32-2.23 (m, 4H), 2.13 (d, 8H),

Example 11

1-[2-[2,4-dioxo-3-(2,4,6-trimethylphenyl)cyclopentyl]ethyl]-3-methyl-urea (Compound A94)

Step 1: Preparation of (2,3,4,5,6-pentafluorophenyl) phenyl carbonate

(71) 2,3,4,5,6-Pentafluorophenol (3.000 g, 16.30 mmol) was dissolved in dichloromethane (10 mL) and pyridine (21.19 mmol) was added followed by drop-wise addition of phenyl carbonochloridate (19.56 mmol) in dichloromethane (10 mL) over 10 mins. The reaction mixture was stirred for 2 hours, then diluted with DCM (20 mL) and quenched with water. The organic layer was dried (MgSO.sub.4) and concentrated in vacuo to give (2,3,4,5,6-pentafluorophenyl) phenyl carbonate (4.878 g, 16.04 mmol, 98% yield) as a solid,

(72) 1H NMR (400 MHz, CDCl.sub.3) 7.48-7.39 (m, 2H), 7.35-7.26 (m, 3H)

Step 2: Preparation of phenyl N-2-[2-methoxy-4-oxo-3-(2,4,6-trimethylphenyl)cyclopent-2-en-1-yl]ethyl]carbamate

(73) 5-(2-Aminoethyl)-3-methoxy-2-(2,4,6-trimethylphenyl)cyclopent-2-en-1-one hydrochloride (4.6 mmol, 4.6 mmol) was dissolved in dichloromethane (50 mL) and N,N-diethylethanamine (9.2 mmol) was added. (2,3,4,5,6-Pentafluorophenyl) phenyl carbonate (4.6 mmol) was added and the reaction mixture was stirred at room temperature for 1.5 hours. The reaction mixture was diluted with 2M HCl and extracted twice with DCM. The organic layers were dried (MgSO.sub.4) and concentrated in vacuo to leave an orange gum which was purified by flash column chromatography using a gradient elution from 5% EtOAc in i-hexane to 100% EtOAc to give phenyl N-2-[2-methoxy-4-oxo-3-(2,4,6-trimethylphenyl)cyclopent-2-en-1-yl]ethyl]carbamate (1.883 g, 4.785 mmol, 100% yield).

(74) 1H NMR (400 MHz, CDCl.sub.3) 7.41-7.34 (m, 2H), 7.24-7.18 (m, 1H), 7.13 (d, 2H), 6.86 (s, 2H), 5.18-5.00 (m, 1H), 3.54 (s, 3H), 3.47-3.34 (m, 2H), 2.99 (br. s., 1H), 2.81 (dd, 1H), 2.32 (dd, 1H), 2.26 (s, 3H), 2.24-2.15 (m, 1H), 2.11 (s, 6H), 1.79-1.66 (m, 1H)

Step 3: Preparation of 1-[2-[2-methoxy-4-oxo-3-(2,4,6-trimethylphenyl)cyclopent-2-en-1-yl]ethyl]-3-methyl-urea

(75) Phenyl N-[2-[2-methoxy-4-oxo-3-(2,4,6-trimethylphenyl)cyclopent-2-en-1-yl]ethyl]carbamate (0.209 g, 0.531 mmol) was dissolved in acetonitrile (3 mL). N,N-Diethylethanamine (1.17 mmol) was added followed by methanamine hydrochloride (0.637 mmol). The reaction mixture was heated in the microwave at 120 C. for 45 mins. The reaction mixture was diluted with water and the pH was adjusted to 7 using 2M HCl. the reaction mixture was extracted twice with EtOAc. The combined organic layers were dried (MgSO.sub.4) and concentrated in vacuo to leave a yellow gum which was purified by flash column chromatography using a gradient elution from DCM to 10% Me0H in DCM to furnish 1-[2-[2-methoxy-4-oxo-3-(2,4,6-trimethylphenyl)cyclopent-2-en-1-yl]ethyl]-3-methyl-urea (0.105 g, 0.318 mmol, 60% yield).

(76) 1H NMR (400 MHz, CDCl.sub.3) 6.86 (s, 2H), 4.43 (t, 1H), 4.28 (d, 1H), 3.55-3.47 (m, 3H), 3.36-3.25 (m, 2H), 3.00-2.86 (m, 1H), 2.83-2.74 (m, 4H), 2.30 (dd, 1H), 2.26 (s, 3H), 2.18-2.11 (m, 1H), 2.10-2.05 (m, 6H), 1.65-1.59 (m, 1H).

Step 4: Preparation of 1-[2-[2,4-dioxo-3-(2,4,6-trimethylphenyl)cyclopentyl]ethyl]-3-methyl-urea

(77) 1-[2-[2-methoxy-4-oxo-3-(2,4,6-trimethylphenyl)cyclopent-2-en-1-yl]ethyl]-3-methyl-urea (0.055 g, 0.17 mmol) was dissolved in acetone (10 mL/mmol) and hydrochloric acid (2 M solutionm, 10 mL/mmol, 3.3 mmol) was added. The reaction mixture was heated at 60 C. for 13 hours, then a further potrion of hydrochloric acid (2 M solutionm 10 mL/mmol, 3.3 mmol) was added and lelft to stirr for 2 hours. The reaction mixture was concentrated in vacuo to furnish 1-[2-[2,4-dioxo-3-(2,4,6-trimethylphenyl)cyclopentyl]ethyl]-.3-methyl-urea (0.0514 g, 0.162 mmol, 98 yield) as a yellow glassy solid.

(78) 1H NMR (400 MHz, CD.sub.3OD) 6.88 (s, 2H), 3.51-3.33 (m, 2H), 2.98 (dd, 1H), 2.84-2.75 (m, 4H), 2.49-2.39 (m, 1H), 2.27-2.22 (m, 3H), 2.10-1.98 (m, 7H), 1.80-1.70 (m, 1H)

Example 12

Preparation of N-[2-[3-(2,4-dimethyl-6-vinyl-phenyl)-2,4-dioxo-cyclopentyl]ethyl]-5,5-dimethyl-4H-isoxazole-3-carboxamide (Compound A122)

Step 1: Preparation of 2-(2-bromo-4,6-dimethyl-phenyl)-3-methoxy-cyclopent-2-en-1-one

(79) 2-(2-Bromo-4,6-dimethyl-phenyl)cyclopentane-1,3-dione (2.500 g, 8.892 mmol) and potassium carbonate sesquihydrate (13.34 mmol) were suspended in acetone (55 mL). Iodomethane (44.46 mmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was poured into 2M HCl and extracted with EtOAc. The organic layers were dried (MgSO.sub.4) and concentrated in vacuo to leave a dark orange oil to give 2-(2-bromo-4,6-dimethyl-phenyl)-3-methoxy-cyclopent-2-en-1-one (2.498 g, 8.463 mmol, 95 yield) which was used in the next step without further purification. 1H NMR (400 MHz, CDCl.sub.3) 7.27 (br. s., 1H), 7.02-6.92 (m, 1H), 3.79 (s, 3H), 2.86-2.74 (m, 2H), 2.71-2.60 (m, 2H), 2.30-2.23 (m, 3H), 2.19-2.11 (m, 3H)

Step 2: Preparation of 2-(2-bromo-4,6-dimethyl-phenyl)-3-methoxy-cyclopent-2-en-1-one

(80) 2-(2-Bromo-4,6-dimethyl-phenyl)-3-methoxy-cyclopent-2-en-1-one (2.498 g, 8.462 mmol) was dissolved in tetrahydrofuran (30 mL/g) and cooled to 70 C. Lithium bis(trimethylsilyl)amide (1M in THF, 9.308 mmol) was added dropwise and the reaction was allowed to stir for 1 hour. 2-Bromoacetonitrile (9.477 mmol) was then added and after 30 mins, the reaction mixture was allowed to warm to 0 C. and stirred for a further 1 hr. The reaction mixture was quenched with 0.5 M NH.sub.4Cl and the reaction mixture was extracted with ethyl acetate. The organic layer was combined, washed with brine, dried (MgSO4) and concentrated. This resulting residue was purified by flash column chromatography using a gradient elution from 5% EtOAc in i-hexane to 100% EtOAc to furnish 2-[3-(2-bromo-4,6-dimethyl-phenyl)-2-methoxy-4-oxo-cyclopent-2-en-1-yl]acetonitrile (0.350 g, 1.05 mmol, 12% yield) and 2-[3-(2-bromo-4,6-dimethyl-phenyl)-4-methoxy-2-oxo-cyclopent-3-en-1-yl]acetonitrile (0.404 g, 1.21 mmol, 14% yield).

(81) 2-[3-(2-bromo-4,6-dimethyl-phenyl)-2-methoxy-4-oxo-cyclopent-2-en-1-yl]acetonitrile: 1H NMR (400 MHz, CDCl.sub.3) 7.29-7.26 (m, 1H), 7.04-6.94 (m, 1H), 3.69-3.61 (m, 3H), 3.24 (ddt, 1H), 2.96-2.82 (m, 2H), 2.71-2.59 (m, 1H), 2.50 (dd, 1H), 2.31-2.27 (m, 3H), 2.17 (s, 3H)

(82) 2-[3-(2-bromo-4,6-dimethyl-phenyl)-4-methoxy-2-oxo-cyclopent-3-en-1-yl]acetonitrile: 1H NMR (400 MHz, CDCl.sub.3) 7.32-7.26 (m, 1H), 7.06-6.87 (m, 1H), 3.75-3.60 (m, 4H), 3.38-3.13 (m, 1H), 2.96-2.74 (m, 2H), 2.57-2.41 (m, 1H), 2.35-2.24 (m, 6H)

Step 3: Preparation of N-[2-3-(2-bromo-4,6-dimethyl-phenyl)-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl]-5,5-dimethyl-4H-isoxazole-3-carboxamide

(83) A glass pressure vessel was charged with raney nickel 2400 (0.200 g, 2.28 mmol) which was subsequently washed with distilled water (35 mL), and the excess water decanted off, leaving the nickel damp. 2-[3-(2-Bromo-4,6-dimethyl-phenyl)-2-methoxy-4-oxo-cyclopent-2-en-1-yl]acetonitrile (0.250 g, 0.748 mmol), (2,3,4,5,6-pentafluorophenyl) 5,5-dimethyl-4H-isoxazole-3-carboxylate (1.05 mmol), and 1,2-dimethoxyethane (20 mL/g) were added to the vessel. The vessel was sealed, purged with nitrogen followed by hydrogen, and stirred at room temperature under 3.5 Bar of hydrogen pressure for 3 hours. The reaction mixture was filtered through celite, washed with methanol, and the combined organic layers were concentrated. The resulting residue was purified by flash column chromatography using a gradient elution from 10% EtOAc in i-hexane to 100% EtOAc to furnish

(84) N-[2-[3-(2-bromo-4,6-dimethyl-phenyl)-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl]-5,5-dimethyl-4H-isoxazole-3-carboxamide (D, 0.070 g, 0.15 mmol, 20% yield).

(85) H NMR (400 MHz, CDCl.sub.3) 7.27-7.16 (m, 1H), 7.02-6.91 (m, 1H), 6.77 (br. s., 1H), 3.65-3.57 (m, 3H), 3.55-3.45 (m, 2H), 3.03-2.97 (m, 2H), 2.97-2.88 (m, 1H), 2.83-2.72 (m, 1H), 2.39-2.30 (m, 1H), 2.28 (s, 3H), 2.19-2.13 (m, 4H), 1.88-1.73 (m, 1H), 1.48-1.37 (m, 6H).

Step 4: Preparation of N-[2-[3-(2,4-dimethyl-6-vinyl-phenyl)-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl]-5,5-dimethyl-4H-isoxazole-3-carboxamide

(86) N-[2-[3-(2-bromo-4,6-dimethyl-phenyl)-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl]-5,5-dimethyl-4H-isoxazole-3-carboxamide (0.070 g, 0.15 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.015 mmol) was dissolved in toluene (14.7 mL/mmol, 21 mmol) and tributyl(vinyl)stannane (0.18 mmol) was added. The reaction mixture was heated to reflux for 2 hr. The mixture was cooled to room temperature diluted with EtOAc, filtered and concentrated. The resulting residue was purified by flash column chromatography using a gradient elution from 0 to 5% MeOH in DCM to furnish N-[2-[3-(2,4-dimethyl-6-vinyl-phenyl)-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl]-5,5-dimethyl-4H-isoxazole-3-carboxamide (0.053 g, 0.13 mmol, 85% yield).

(87) 1H NMR (400 MHz, CDCl.sub.3) 7.24-7.19 (m, 1H), 6.96 (s, 1H), 6.77 (br. s., 1H), 6.54 (dd, 1H), 5.63 (ddd, 1H), 5.24-5.14 (m, 1H), 3.56-3.42 (m, 5H), 3.00 (d, 2H), 3.00-2.93 (m, 1H), 2.81 (ddd, 1H), 2.34-2.29 (m, 4H), 2.16 (dd, 1H), 2.12-2.06 (m, 3H), 1.78-1.63 (m, 1H), 1.48-1.41 (m, 6H)

Step 5: Preparation of N-[2-[3-(2,4-dimethyl-6-vinyl-phenyl)-2,4-dioxo-cyclopentyl]ethyl]-5,5-dimethyl-4H-isoxazole-3-carboxamide

(88) N-[2-[3-(2,4-Dimethyl-6-vinyl-phenyl)-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl]-5,5-dimethyl-4H-isoxazole-3-carboxamide (0.053 g, 0.13 mmol) was suspended in acetone (5.89 mL/mmol) and hydrochloric acid (2M solution, 5.89 mL/mmol, 1.5 mmol) was added.

(89) The reaction mixture was heated at 60 C. for 4 hours, then cooled to room temperature. The mixture was concentrated in vacuo to give N-[2-[3-(2,4-dimethyl-6-vinyl-phenyl)-2,4-dioxo-cyclopentyl]ethyl]-5,5-dimethyl-4H-isoxazole-3-carboxamide (0.025 g, 0.063 mmol, 49% yield) as a yellow foam.

(90) 1HNMR (400 MHz, CD3OD) 7.26 (d, 1H), 7.02-6.92 (m, 1H), 6.59-6.42 (m, 1H), 5.60 (ddd, 1H), 5.15-5.04 (m, 1H), 3.50-3.37 (m, 2H), 3.01-2.97 (m, 2H), 2.95-2.71 (m, 2H), 2.47 (d, 1H), 2.33-2.26 (m, 3H), 2.21-2.08 (m, 1H), 2.05 (d, 3H), 1.72-1.60 (m, 1H), 1.46-1.39 (m, 6H)

Example 13

Preparation of N-[2-[3-(2-ethynyl-4,6-dimethyl-phenyl)-2,4-dioxo-cyclopentyl]ethyl]-5,5-dimethyl-4H-isoxazole-3-carboxamide (A123)

Step 1: Preparation of N-[2-[3-[2,4-dimethyl-6-(2-trimethylsilylethynyl)phenyl]-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl]-5,5-dimethyl-4H-isoxazole-3-carboxamide

(91) N-[2-[3-(2-Bromo-4,6-dimethyl-phenyl)-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl]-5,5-dimethyl-4H-isoxazole-3-carboxamide (0.080 g, 0.17 mmol), trimethyl(2-tributylstannylethynyl)silane (0.21 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.017 mmol) was suspended in toluene (2 mL, 18.7 mmol). The mixture was heated under reflux for 3 h. A further portion of trimethyl(2-tributylstannylethynyl)silane (0.21 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.017 mmol) were added and the reaction mixture was heated for a further 2 hours. The reaction mixture was cooled to room temperature diluted with EtOAc and filtered through MgSO4. The filtrate was concentrated in vacuo and the resulting residue was purified by flash column chromatography using a gradient elution from DCM to 5% MeOH in DCM to furnish N-[2-[3-[2,4-dimethyl-6-(2-trimethylsilylethynyl)phenyl]-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl]-5,5-dimethyl-4H-isoxazole-3-carboxamide (0.059 g, 0.12 mmol, 71% yield).

(92) 1H NMR (400 MHz, CDCl3) 7.21-7.13 (m, 1H), 7.02-6.95 (m, 1H), 6.77 (d, 1H), 3.62 (d, 3H), 3.56-3.43 (m, 2H), 3.00 (d, 2H), 2.97-2.85 (m, 1H), 2.82-2.68 (m, 1H), 2.34-2.29 (m, 1H), 2.29-2.23 (m, 3H), 2.17-2.11 (m, 3H), 1.83-1.62 (m, 1H), 1.49-1.41 (m, 6H), 1.41-1.28 (m, 1H), 0.21-0.16 (m, 9H)

Step 2: Preparation of N-[2-[3-(2-ethynyl-4,6-dimethyl-phenyl)-2,4-dioxo-cyclopentyl]ethyl]-5,5-dimethyl-4H-isoxazole-3-carboxamide

(93) N-[2-[3-[2,4-Dimethyl-6-(2-trimethylsilylethynyl)phenyl]-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl]-5,5-dimethyl-4H-isoxazole-3-carboxamide (0.059 g, 0.12 mmol) was suspended in acetone (5.89 mL/mmol) and hydrochloric acid (2M solution, 5.89 mL/mmol, 1.4 mmol) was added. The reaction mixture was heated at 60 C. for 5 hour 30 min then cooled to room temperature. More acetone (5.89 mL/mmol) and hydrochloric acid (2M solution, 5.89 mL/mmol, 1.4 mmol) were added to the reaction mixture which was heated for a further 5 hours. The reaction mixture was concentrated to remove the acetone and the residue was extracted twice with EtOAc. The organic layers were dried (MgSO.sub.4) and concentrated in vacuo and the resulting residue was purified by flash column chromatography using a gradient elution from DCM to 10% MeOH in DCM to furnish N-[2-[3-(2-ethynyl-4,6-dimethyl-phenyl)-2,4-dioxo-cyclopentyl]ethyl]-5,5-dimethyl-4H-isoxazole-3-carboxamide (0.013 g, 0.033 mmol, 27% yield).

(94) 1H NMR (400 MHz, CD.sub.3OD) 7.38 (s, 1H), 7.25 (s, 1H), 3.57-3.38 (m, 2H), 3.04-2.94 (m, 2H), 2.97-2.82 (m, 1H), 2.79-2.66 (m, 1H), 2.47 (s, 1H), 2.43 (br. s., 1H), 2.38 (s, 3H), 2.15 (s, 3H), 2.14-2.05 (m, 1H), 1.81-1.60 (m, 1H), 1.42 (d, 6H)

Example 14

Chiral HPLC or SFC Separation of Enantiomers

(95) In one optional embodiment of the invention, any specific compound of the invention is separated into the two corresponding enantiomerically pure (or subtantially enantiomerically pure) compounds using a chiral HPLC or SFC column. In one optional example, the chiral HPLC uses the following method and the following conditions.

(96) Chiral HPLC column: a (s,s) WhelkO15 micron21 mm250 mm HPLC column, manufactured by Regis Technologies, Inc. In this column, the chiral stationary phase is (S,S) 1-(3-5-dinitrobenzamido)-1,2,3,4-tetrahydrophenanthrene.

(97) The solvent system to be used as an eluent for the column varies depending on the racemic compound to be separated into enantiomers, but one example of a solvent system is: a 30:70 (by volume) mixture of Solvent A and Solvent B, in which:

(98) Solvent A is isohexane containing 0.1% v/v of trifluoroacetic acid (TFA), and Solvent B is ethanol.

(99) Other conditions (these are sample conditions only and may vary widely):

(100) Flow rate through column: about 21 ml/minute. Run time: about 20 minutes.

(101) Loading (compound loaded onto column): about 50 mg/ml of compound in ethanol.

(102) Volume of sample (compound) injected per run=about 1800 microliters.

(103) Number of injections of compound=about 5.

(104) Abbreviation:

(105) HPLC=high performance (or high pressure) liquid chromatography.

(106) SFC=Supercritical fluid chromatography

(107) General Note on Chiral HPLC or SFC Separation of Enantiomers:

(108) In one optional embodiment, the above procedure using chiral HPLC is used to separate the enantiomers of other compounds of formula (I) of the present the invention. Alternative chiral columns which might be useful to achieve this are as follows:

(109) (s,s) WhelkO15 micron21 mm250 mm HPLC column, manufactured by Regis Technologies, Inc [in this column, the chiral stationary phase is (S,S) 1-(3-5-dinitrobenzamido)-1,2,3,4-tetrahydrophenanthrene];

(110) Kromasil AmyCoat [whose chiral stationary phase is tris-(3,5-dimethylphenyl)carbamoyl amylose];

(111) Kromasil CelluCoat [whose chiral stationary phase is tris-(3,5-dimethylphenyl)carbamoyl cellulose];

(112) Chiralpak IA [whose chiral stationary phase is a (3,5-dimethylphenyl)carbamate derivative of amylose];

(113) Chiralpak IB [whose chiral stationary phase is tris-(3,5-dimethylphenyl)carbamate derivative of cellulose];

(114) Chiralpak IC [whose chiral stationary phase is cellulose tris(3,5-dichlorophenyl) carbamate];

(115) Lux Amylose-2 [whose chiral stationary phase is amylose tris(5-chloro-2-methylphenylcarbamate)]; or

(116) Lux Cellulose-2 [whose chiral stationary phase is Cellulose tris(3-chloro-4-methylphenylcarbamate)].

(117) Lux Cellulose-4 [whose chiral stationary phase is Cellulose tris(4-chloro-3-methylphenylcarbamate)]

(118) Chiral HPLC Separation of Enantiomers of Compound A122 to Compounds A122a and A122b.

(119) ##STR00033##

(120) Compound A122 (racemic), was separated into the enantiomers A122a and A122b using a chiral SFC column, by the following method and under the following conditions.

(121) The chiral SFC column used was Lux C4 (21.2 mm250 mm, 5 um).

(122) The solvent system used as an eluent for the column was a 40:60 (by volume) mixture of methanol and supercritical carbon dioxide with 0.1% TEA.

(123) Other conditions were as follows:

(124) Flow rate through column: 50 ml/minute.

(125) Volume of sample (compound) injected per run=0.2 mL (10 mg)

(126) Length of run=8 minutes

(127) Detection wavelength=230 nm

(128) Chiral SFC on a total of 2.59 g of compound A122 under the above conditions gave 1.08 g of compound A122a (99.3% enantiomeric excess (e.e.), retention time 5.67 minutes under the above conditions) and 1.01 g of compound A122b (99% enantiomeric excess (e.e.), retention time 6.39 minutes under the above conditions).

(129) Abbreviation: SFC=Supercritical fluid chromatography

(130) Additional compounds in Table T1 below illustrate the present invention, and are particular embodiments of the compounds of formula (I) according to the present invention. For the most part, these compounds can generally be prepared by methods similar to those shown in the Examples and/or in the process section hereinabove using appropriate starting materials.

(131) TABLE-US-00010 TABLE T1 It should be noted that certain compounds of the invention may exist as a mixture of isomers, including sometimes atropisomers, e.g. as noted above, under the conditions used to obtain the .sup.1H NMR data. Where this has occurred, the characterising data are reported for all isomers present at ambient temperature in the specified solvent. Unless otherwise stated, proton (.sup.1H) NMR spectra disclosed herein were recorded at ambient temperature. Compound Number Chemical Structure NMR A1 1H NMR (400 MHz, d4-methanol) 1.68- 1.78 (1H, m), 2.03- 2.08 (6H, s), 2.13- 2.21 (1H, m), 2.22- 2.26 (3H, s), 2.44- 2.52 (1H, dd), 2.77- 2.84 (1H, m), 2.88- 2.97 (1H, dd), 3.48- 3.54 (2H, dt), 6.83- 6.87 (2H, s), 7.59- 7.64 (1H, m), 7.97- 8.03 (1H, dt), 8.16- 8.22 (1H, d), 8.64- 8.68 (1H, d) A2 1HNMR(400 MHz, d4-methanol) 8.47- 8.36 (m, 1H), 7.60 (s, 1H), 7.42 (d, 1H), 6.88 (s, 2H), 3.56- 3.47 (m, 2H), 2.97 (dd, 1H), 2.89-2.77 (m, 1H), 2.50 (dd, 1H), 2.27 (s, 3H), 2.17 (d, 1H), 2.10- 2.00 (m, 6H), 1.82- 1.69 (m, 1H) A3 1HNMR(400 MHz, d4-methanol) 8.36- 8.19 (m, 2H), 7.45- 7.32 (m, 2H), 6.91- 6.83 (m, 2H), 3.54- 3.41 (m, 2H), 2.99 (dd, 1H), 2.88-2.77 (m, 1H), 2.51 (dd, 1H), 2.30-2.24 (m, 3H), 2.21-2.10 (m, 1H), 2.09-2.02 (m, 6H), 1.78-1.67 (m, 1H) A4 1HNMR(400 MHz, d4-methanol) 8.38 (d, 1H), 8.31 (dd, 1H), 7.26 (d, 1H), 6.89 (s, 2H), 3.51- 3.44 (m, 2H), 3.02- 2.95 (m, 1H), 2.82 (td, 1H), 2.49 (dd, 1H), 2.27-2.22 (m, 3H), 2.17-2.11 (m, 1H), 2.06 (d, 6H), 1.81-1.67 (m, 1H) A5 1HNMR(400 MHz, d4-methanol) 6.86 (s, 2H), 3.28-3.06 (m, 2H), 2.88 (dd, 1H), 2.75 (br.s., 1H), 2.40 (d, 1H), 2.25 (s, 3H), 2.07-2.01 (m, 6H), 2.01-1.91 (m, 1H), 1.64-1.53 (m, 1H), 1.30 (s, 9H) A6 1HNMR(400 MHz, d4-methanol) 6.87- 6.81 (m, 2H), 3.28- 3.20 (m, 2H), 2.93- 2.84 (m, 1H), 2.46- 2.37 (m, 1H), 2.25 (s, 3H), 2.04 (d, 6H), 2.02-1.96 (m, 1H), 1.66-1.55 (m, 1H), 0.21-0.20 (m, 1H) A7 0 1HNMR(400 MHz, d4-methanol) 7.34- 7.26 (m, 4H), 7.26- 7.18 (m, 1H), 6.87 (s, 2H), 4.33 (s, 2H), 3.40-3.31 (m, 2H), 2.89 (dd, 1H), 2.80- 2.69 (m, 1H), 2.42 (dd, 1H), 2.25 (s, 3H), 2.04 (d, 6H), 2.04-1.95 (m, 1H), 1.69-1.55 (m, 1H) A8 1HNMR(400 MHz, d4-methanol) 7.46- 7.40 (m, 2H), 7.35- 7.26 (m, 3H), 6.86 (s, 2H), 3.28-3.21 (m, 5H), 2.88 (dd, 1H), 2.76-2.66 (m, 1H), 2.42 (d, 1H), 2.25 (s, 3H), 2.03 (d, 6H), 2.01-1.91 (m, 1H), 1.64-1.50 (m, 1H) A9 1HNMR(400 MHz, d4-methanol) 7.38- 7.31 (m, 2H), 7.27- 7.18 (m, 2H), 7.00- 6.92 (m, 1H), 6.86 (s, 2H), 3.42-3.33 (m, 2H), 2.95-2.75 (m, 2H), 2.48-2.41 (m, 1H), 2.25 (s, 3H), 2.12-2.06 (m, 1H), 2.05 (s, 6H), 1.66 (qd, 1H) A10 1HNMR(400 MHz, d4-methanol) 7.36- 7.28 (m, 2H), 7.29- 7.20 (m, 3H), 6.90- 6.80 (m, 2H), 4.58- 4.48 (m, 2H), 3.48- 3.32 (m, 2H), 2.94 (dd, 1H), 2.87 (s, 3H), 2.82-2.71 (m, 1H), 2.48-2.40 (m, 1H), 2.25 (s, 3H), 2.08-1.98 (m, 7H), 1.77-1.61 (m, 1H) A11 1HNMR(400 MHz, d4-methanol) 8.47- 8.32 (m, 2H), 7.74- 7.64 (m, 1H), 7.55- 7.42 (m, 1H), 6.88- 6.79 (m, 2H), 3.55- 3.45 (m, 2H), 3.34- 3.28 (m, 3H), 3.04- 2.94 (m, 1H), 2.88- 2.80 (m, 1H), 2.54- 2.46 (m, 1H), 2.25- 2.22 (m, 3H), 2.22- 2.15 (m, 1H), 2.10- 2.00 (m, 6H), 1.80- 1.69 (m, 1H) A12 1HNMR(400 MHz, d4-methanol,) 8.31- 8.21 (m, 2H), 7.42 (dd, 1H), 6.90-6.78 (m, 2H), 3.46 (t, 2H), 3.04-2.91 (m, 1H), 2.85-2.77 (m, 1H), 2.54-2.42 (m, 1H), 2.24 (s, 3H), 2.21- 2.09 (m, 1H), 2.07- 2.01 (m, 6H), 1.78- 1.67 (m, 1H) A13 1HNMR(400 MHz, d4-methanol) 8.34 (s, 1H), 8.31-8.20 (m, 2H), 7.67 (s, 1H), 7.44 (s, 2H), 7.42- 7.33 (m, 2H), 3.50 (t, 2H), 3.04 (dd, 1H), 2.87 (br.s., 1H), 2.55 (d, 1H), 2.18 (s, 7H), 1.80-1.64 (m, 1H) A14 1HNMR(400 MHz, CDCl3) 6.90-6.79 (m, 2H), 3.86-3.70 (m, 1H), 3.54-3.43 (m, 1H), 3.15-3.04 (m, 1H), 2.91-2.83 (m, 2H), 2.83-2.79 (m, 3H), 2.26-2.20 (m, 3H), 2.13-2.01 (m, 6H), 1.97-1.84 (m, 1H), 1.77-1.62 (m, 1H), 1.41-1.35 (m, 9H) A15 1HNMR(400 MHz, d4-methanol) 6.92- 6.82 (m, 2H), 6.20 (s, 1H), 3.45-3.33 (m, 2H), 2.92 (dd, 1H), 2.83-2.73 (m, 1H), 2.46 (dd, 1H), 2.28-2.21 (m, 3H), 2.17-2.07 (m, 1H), 2.07-1.97 (m, 6H), 1.73-1.59 (m, 1H), 1.35-1.30 (m, 9H) A16 1HNMR(400 MHz, d4-methanol) 8.89 (s, 1H), 7.93 (s, 1H), 6.92-6.79 (m, 2H), 3.52-3.41 (m, 2H), 2.94 (dd, 1H), 2.87- 2.73 (m, 1H), 2.48 (dd, 1H), 2.28-2.21 (m, 3H), 2.19-2.06 (m, 1H), 2.05 (d, 6H), 1.82-1.77 (m, 3H), 1.76-1.72 (m, 4H) A17 0 1HNMR(400 MHz, CDCl3) 8.26 (d, 2H), 7.57 (d, 1H), 7.41 (t, 1H), 6.89 (s, 2H), 3.22-2.98 (m, 5H), 2.83 (d, 1H), 2.48 (d, 1H), 2.32-2.23 (m, 4H), 2.13 (d, 8H), A18 1HNMR(400 MHz, d4-methanol,) 6.89- 6.81 (m, 2H), 3.36 (t, 2H), 3.30 (s, 3H), 2.91 (dd, 1H), 2.76 (d, 1H), 2.48-2.38 (m, 1H), 2.25 (s, 3H), 2.09 (d, 1H), 2.04 (s, 6H), 1.70-1.59 (m, 1H) A19 1HNMR(400 MHz, d4-methanol) 8.50 (d, 1H), 8.33-8.22 (m, 2H), 7.91-7.81 (m, 1H), 7.61 (s, 2H), 7.40 (t, 1H), 7.31 (d, 1H), 3.51-3.45 (m, 3H), 3.02 (dd, 1H), 2.85 (br.s., 1H), 2.59-2.44 (m, 1H), 2.19 (d, 6H), 1.77 (br.s., 1H) A20 1HNMR(400 MHz, CDCl3) 11.00 (br.s., 1H), 8.31 (dd, 1H), 7.87-7.85 (m, 1H), 7.84-7.76 (m, 1H), 7.64-7.57 (m, 1H), 7.38-7.31 (m, 2H), 7.10-7.01 (m, 2H), 4.04-3.84 (m, 1H), 3.48-3.41 (m, 3H), 3.40-3.26 (m, 1H), 3.03 (d, 1H), 2.94- 2.84 (m, 1H), 2.24 (d, 6H), 2.20-2.07 (m, 2H), 1.89-1.73 (m, 1H) A21 1HNMR(400 MHz, d4-methanol) 8.36- 8.29 (m, 1H), 7.66 (s, 1H), 7.44 (s, 2H), 3.29-3.16 (m, 2H), 2.95 (dd, 1H), 2.86- 2.74 (m, 1H), 2.46 (dd, 1H), 2.21-2.12 (m, 6H), 2.04-1.94 (m, 1H), 1.72-1.58 (m, 1H), 1.36-1.29 (m, 9H) A22 1HNMR(400 MHz, d4-methanol) 8.48- 8.37 (m, 2H), 7.72 (d, 1H), 7.54 (t, 1H), 7.07 (s, 2H), 3.56- 3.46 (m, 5H), 3.02 (dd, 1H), 2.89-2.78 (m, 1H), 2.53 (ddz, 1H), 2.25-2.14 (m, 1H), 2.07 (d, 6H), 2.01 (s, 3H), 1.84- 1.67 (m, 1H) A23 1HNMR(400 MHz, d4-methanol) 7.06 (s, 2H), 3.30-3.13 (m, 2H), 2.96-2.85 (m, 1H), 2.76 (br.s., 1H), 2.42 (d, 1H), 2.07 (d, 6H), 2.03- 1.94 (m, 4H), 1.70- 1.54 (m, 1H), 1.32 (s, 9H) A24 1HNMR(400 MHz, d4-methanol) 8.65 (dd, 1H), 8.53-8.42 (m, 1H), 8.25-8.12 (m, 2H), 7.99 (ddd, 1H), 7.46 (s, 2H), 7.34-7.22 (m, 2H), 3.39 (t, 2H), 3.03- 2.91 (m, 1H), 2.82- 2.73 (m, 1H), 2.48 (dd1H), 2.15 (d, 6H), 2.12-2.02 (m, 1H), 1.69-1.59 (m, 1H) A25 1HNMR(400 MHz, d4-methanol) 8.35 (s, 1H), 7.68 (s, 1H), 7.48-7.39 (m, 2H), 3.43-3.36 (m, 2H), 2.97 (dd, 1H), 2.80 (br.s., 1H), 2.50 (dd, 1H), 2.22-2.17 (m, 6H), 2.10 (dd, 1H), 1.73-1.63 (m, 1H), 1.28-1.25 (m, 9H) A26 1HNMR(400 MHz, d4-methanol) 6.88 (s, 2H), 3.39 (t, 2H), 2.93 (dd, 1H), 2.84- 2.74 (m, 1H), 2.46 (dd, 1H), 2.27 (s, 3H), 2.15-2.08 (m, 1H), 2.06 (s, 6H), 1.66 (tdd, 1H) A27 0 1HNMR(400 MHz, d4-methanol) 8.71 (d, 1H), 8.51-8.38 (m, 2H), 8.25 (dd, 1H), 7.74 (d, 1H), 7.59 (s, 2H), 7.55- 7.49 (m, 1H), 3.59- 3.49 (m, 5H), 3.15- 3.02 (m, 1H), 2.95- 2.86 (m, 1H), 2.60 (dd, 1H), 2.32-2.17 (m, 7H), 1.85-1.72 (m, 1H) A28 1HNMR(400 MHz, d4-methanol) 8.35 (s, 1H), 8.32-8.29 (m, 1H), 8.28-8.24 (m, 1H), 7.68 (s, 1H), 7.47 (s, 2H), 7.42 (dd, 1H), 3.50 (t, 2H), 3.03 (dd, 1H), 2.91-2.82 (m, 1H), 2.54 (dd, 1H), 2.36- 2.21 (m, 1H), 2.22- 2.13 (m, 6H), 1.82- 1.70 (m, 1H) A29 1HNMR(400 MHz, d4-methanol) 8.52- 8.40 (m, 1H), 7.81 (dd, 1H), 7.58 (s, 2H), 3.31-3.15 (m, 2H), 2.86 (dd, 1H), 2.78-2.68 (m, 1H), 2.39 (dd, 1H), 2.25- 2.14 (m, 6H), 2.06- 1.97 (m, 1H), 1.60 (qd, 1H), 1.36-1.26 (m, 9H) A30 1HNMR(400 MHz, d4-methanol) 8.61- 8.47 (m, 2H), 7.00 (t, 1H), 6.86-6.71 (m, 2H), 3.55-3.44 (m, 2H), 2.83-2.74 (m, 1H), 2.71-2.60 (m, 1H), 2.34 (dd, 1H), 2.22 (s, 3H), 2.21-2.13 (m, 1H), 2.09-2.04 (m, 6H), 1.70 (tdd, 1H) A31 1HNMR(400 MHz, d4-methanol) 6.93- 6.81 (m, 2H), 3.57- 3.47 (m, 1H), 3.41- 3.33 (m, 1H), 3.05 (dd, 1H), 3.01-2.97 (m, 6H), 2.95-2.84 (m, 1H), 2.48 (dd, 1H), 2.26 (s, 3H), 2.07-2.01 (m, 6H), 1.99-1.79 (m, 2H) A32 1HNMR(400 MHz, d4-methanol) 8.61- 8.54 (m, 2H), 8.36- 8.28 (m, 1H), 7.65 (s, 1H), 7.49-7.36 (m, 2H), 7.10-6.99 (m, 1H), 3.60-3.47 (m, 2H), 3.04-2.93 (m, 1H), 2.91-2.81 (m, 1H), 2.53 (dd, 1H), 2.21-2.11 (m, 7H), 1.78 (tdd, 1H) A33 1HNMR(400 MHz, d4-methanol) 9.09- 8.93 (m, 1H), 8.66- 8.54 (m, 1H), 8.36- 8.29 (m, 1H), 8.31- 8.04 (m, 1H), 7.70- 7.58 (m, 1H), 7.46- 7.32 (m, 2H), 3.48 (t, 2H), 3.07-2.97 (m, 1H), 2.89-2.80 (m, 1H), 2.61-2.46 (m, 1H), 2.22-2.12 (m, 7H), 1.74 (tdd, 1H) A34 1HNMR(400 MHz, d4-methanol) 8.21 (s, 1H), 7.62-7.53 (m, 1H), 6.90-6.81 (m, 2H), 6.60 (d, 1H), 3.63-3.45 (m, 2H), 2.96-2.80 (m, 2H), 2.48-2.39 (m, 1H), 2.24 (s, 3H), 2.20-2.09 (m, 1H), 2.05 (s, 6H), 1.84- 1.68 (m, 1H) A35 1HNMR(400 MHz, d4-methanol) 7.71 (s, 1H), 7.48-7.38 (m, 2H), 6.87 (s, 2H), 3.86-3.68 (m, 2H), 3.02 (dd, 1H), 2.95- 2.84 (m, 1H), 2.58- 2.47 (m, 1H), 2.30- 2.26 (m, 1H), 2.26- 2.20 (m, 3H), 2.06 (d, 6H), 1.98-1.88 (m, 1H) A36 1HNMR(400 MHz, d4-methanol) 8.33- 8.23 (m, 1H), 8.20- 8.08 (m, 1H), 6.88 (s, 2H), 3.86-3.77 (m, 1H), 3.74-3.67 (m, 1H), 3.02 (dd, 1H), 2.90-2.79 (m, 1H), 2.56-2.43 (m, 1H), 2.26 (s, 3H), 2.15 (qd, 1H), 2.09- 2.03 (m, 6H), 2.00- 1.89 (m, 1H) A37 0 1HNMR(400 MHz, dMSO-d6) 7.62 (s, 1H), 7.08 (d, 2H), 6.91 (s, 1H), 6.84 (d, 2H), 6.68 (s, 2H), 2.25 (t, 2H), 2.11 (dd, 1H), 2.01 (br.s., 1H), 1.60 (d, 1H), 1.42-1.32 (m, 6H), 1.24 (s, 1H), 0.83 (d, 1H) A38 1HNMR(400 MHz, CDCl3) 7.82 (s, 1H), 7.55 (s, 1H), 7.19 (s, 3H), 3.96 (s, 3H), 3.69-3.44 (m, 1H), 3.42-3.22 (m, 1H), 2.95-2.64 (m, 2H), 2.33-2.16 (m, 1H), 2.16-1.87 (m, 10H), 1.87-1.62 (m, 1H) A39 1HNMR(400 MHz, CDCl3) 7.31-7.13 (m, 1H), 6.82 (s, 2H), 3.96 (s, 3H), 3.63- 3.42 (m, 1H), 3.40- 3.19 (m, 1H), 2.73 (d, 2H), 2.26-1.84 (m, 14H), 1.82-1.67 (m, 1H) A40 1HNMR(400 MHz, CDCl3) 7.43-7.29 (m, 1H), 6.82 (s, 2H), 3.63-3.22 (m, 2H), 2.93 (s, 2H), 2.82- 2.59 (m, 2H), 2.29- 2.11 (m, 4H), 2.10- 1.63 (m, 8H), 1.43 (d, 6H) A41 1HNMR(400 MHz, CDCl3) 7.82 (s, 1H), 7.56 (s, 1H), 7.45- 7.16 (m, 8H), 5.21 (s, 2H), 3.91-3.48 (m, 1H), 3.42-3.20 (m, 1H), 3.00-2.63 (m, 2H), 2.36-1.99 (m, 11H), 1.96-1.73 (m, 1H) A42 1HNMR(400 MHz, CDCl3) 7.79 (s, 1H), 7.53 (s, 1H), 7.38- 7.29 (m, 1H), 7.13 (s, 2H), 4.20 (s, 3H), 3.55-3.38 (m, 2H), 2.96-2.59 (m, 2H), 2.40-2.23 (m, 1H), 2.12-1.91 (m, 7H), 1.84-1.60 (m, 1H) A43 1HNMR(400 MHz, CDCl3) 7.83 (s, 1H), 7.57 (s, 1H), 7.46- 7.33 (m, 1H), 7.22 (s, 2H), 3.41 (s, 2H), 2.96 (s, 2H), 2.90- 2.68 (m, 2H), 2.33- 2.20 (m, 1H), 2.16- 1.88 (m, 7H), 1.87- 1.67 (m, 1H), 1.44 (s, 6H) A44 1HNMR(400 MHz, CDCl3) 7.45-7.09 (m, 6H), 6.82 (s, 2H), 5.19 (s, 2H), 3.67- 3.40 (m, 1H), 3.39- 3.20 (m, 1H), 2.86- 2.55 (m, 2H), 2.24- 1.97 (m, 13H), 1.95- 1.65 (m, 2H) A45 1H NMR (400 MHz, d4-methanol) 8.04- 7.93 (m, 1H), 7.18- 7.06 (m, 2H), 7.06- 6.95 (m, 1H), 6.89 (s, 2H), 3.46-3.36 (m, 2H), 2.95 (dd, 1H), 2.82 (br. s., 1H), 2.55-2.42 (m, 1H), 2.34-2.21 (m, 3H), 2.19-2.02 (m, 7H), 1.77-1.60 (m, 1H) A46 1H NMR (400 MHz, d4-methanol) 7.95- 7.84 (m, 2H), 7.64- 7.54 (m, 1H), 7.54- 7.45 (m, 2H), 6.86 (s, 2H), 3.55-3.45 (m, 2H), 2.93 (dd, 1H), 2.87-2.77 (m, 1H), 2.48 (dd, 1H), 2.24 (s, 3H), 2.22- 2.11 (m, 1H), 2.10- 1.99 (m, 6H), 1.72 (tdd, 1H) A47 0 1H NMR (400 MHz, d4-methanol) 6.89 (s, 2H), 3.72-3.61 (m, 4H), 3.45-3.26 (m, 6H), 2.94 (dd, 1H), 2.83-2.73 (m, 1H), 2.45 (dd, 1H), 2.28 (s, 3H), 2.15- 1.99 (m, 7H), 1.75- 1.58 (m, 1H) A48 1H NMR (400 MHz, d4-methanol) 7.53 (tt, 1H), 7.14-7.02 (m, 2H), 6.87 (s, 2H), 3.56-3.41 (m, 2H), 2.93 (dd, 1H), 2.85- 2.74 (m, 1H), 2.54- 2.40 (m, 1H), 2.29- 2.22 (m, 3H), 2.22- 2.10 (m, 1H), 2.08- 2.03 (m, 6H), 1.80- 1.64 (m, 1H) A49 1H NMR (400 MHz, d4-methanol) 7.51- 7.30 (m, 4H), 6.83 (s, 2H), 3.50-3.38 (m, 2H), 2.94-2.83 (m, 1H), 2.77 (dd, 1H), 2.50-2.36 (m, 1H), 2.26-2.18 (m, 3H), 2.18-2.07 (m, 1H), 2.05-1.97 (m, 6H), 1.68 (tdd, 1H) A50 1H NMR (400 MHz, d4-methanol) 7.44- 7.29 (m, 2H), 7.27- 7.16 (m, 2H), 6.83 (s, 2H), 3.47-3.39 (m, 2H), 2.93-2.82 (m, 1H), 2.80-2.70 (m, 1H), 2.47-2.34 (m, 4H), 2.21 (s, 3H), 2.18-2.07 (m, 1H), 2.05-1.96 (m, 6H), 1.74-1.59 (m, 1H) A51 1H NMR (400 MHz, d4-methanol) 7.97- 7.83 (m, 2H), 7.59- 7.48 (m, 2H), 6.89 (s, 2H), 3.53 (t, 1H), 2.96 (dd, 1H), 2.89- 2.74 (m, 1H), 2.56- 2.44 (m, 1H), 2.32- 2.13 (m, 5H), 2.12- 1.97 (m, 6H), 1.75 (tdd, 1H) A52 1H NMR (400 MHz, d4-methanol) 7.45- 7.28 (m, 3H), 6.83 (s, 2H), 3.50-3.36 (m, 2H), 2.88 (dd, 1H), 2.75 (br. s., 1H), 2.44 (d, 1H), 2.25-2.08 (m, 4H), 2.06-1.93 (m, 6H), 1.75-1.61 (m, 1H) A53 1H NMR (400 MHz, d4-methanol) 7.90- 7.69 (m, 1H), 7.20- 7.04 (m, 2H), 6.89 (s, 2H), 3.57-3.42 (m, 2H), 2.96 (dd, 1H), 2.88-2.76 (m, 1H), 2.51 (dd, 1H), 2.34-2.14 (m, 4H), 2.13-2.01 (m, 6H), 1.75 (tdd, 1H) A54 1H NMR (400 MHz, d4-methanol) 7.71 (dt, 1H), 7.58-7.48 (m, 1H), 7.30-7.12 (m, 2H), 6.82 (s, 2H), 3.50-3.39 (m, 2H), 2.88 (dd, 1H), 2.80- 2.69 (m, 1H), 2.43 (dd, 1H), 2.20 (s, 3H), 2.18-2.05 (m, 1H), 2.05-1.96 (m, 6H), 1.67 (tdd, 1H) A55 1H NMR (400 MHz, d4-methanol) 7.88- 7.76 (m, 2H), 7.40- 7.26 (m, 2H), 6.89 (s, 2H), 3.58-3.47 (m, 2H), 2.96 (dd, 1H), 2.89-2.78 (m, 1H), 2.57-2.46 (m, 1H), 2.44 (s, 3H), 2.27 (s, 3H), 2.24- 2.13 (m, 1H), 2.11- 2.02 (m, 6H), 1.75 (tdd, 1H) A56 1H NMR (400 MHz, d4-methanol) 7.97- 7.72 (m, 2H), 7.50- 7.38 (m, 1H), 6.89 (s, 2H), 3.53 (t, 2H), 2.96 (dd, 1H), 2.88- 2.78 (m, 1H), 2.51 (dd, 1H), 2.33-2.14 (m, 4H), 2.08 (s, 6H), 1.75 (tdd, 1H) A57 0 1H NMR (400 MHz, d4-methanol) 7.97- 7.87 (m, 2H), 7.08- 6.99 (m, 2H), 6.89 (s, 2H), 3.91-3.86 (m, 3H), 3.57-3.48 (m, 2H), 2.96 (dd, 1H), 2.89-2.78 (m, 1H), 2.51 (dd, 1H), 2.27 (s, 3H), 2.24- 2.13 (m, 1H), 2.11- 2.03 (m, 6H), 1.75 (tdd, 1H) A58 1H NMR (400 MHz, d4-methanol) 8.15- 8.03 (m, 1H), 7.89- 7.77 (m, 1H), 7.71- 7.65 (m, 1H), 6.88 (s, 2H), 3.53 (t, 2H), 3.01-2.90 (m, 1H), 2.89-2.77 (m, 1H), 2.56-2.43 (m, 1H), 2.31-2.15 (m, 4H), 2.11-1.98 (m, 6H), 1.75 (tdd, 1H) A59 1H NMR (400 MHz, d4-methanol) 7.69 (t, 1H), 7.37-7.25 (m, 1H), 6.82 (s, 2H), 6.87 (br. s., 1H), 3.49-3.39 (m, 2H), 2.88 (dd, 1H), 2.80- 2.70 (m, 1H), 2.43 (dd, 1H), 2.24-2.07 (m, 4H), 2.06-1.95 (m, 6H), 1.67 (tdd, 1H) A60 1H NMR (400 MHz, d4-methanol) 7.78- 7.71 (m, 1H), 7.70- 7.58 (m, 2H), 7.55 (d, 1H), 6.83 (s, 2H), 3.49-3.39 (m, 2H), 2.88 (dd, 1H), 2.80- 2.70 (m, 1H), 2.43 (dd, 1H), 2.21 (s, 3H), 2.18-2.08 (m, 1H), 2.03 (s, 6H), 1.67 (tdd, 1H) A61 1H NMR (400 MHz, d4-methanol) 7.89- 7.71 (m, 3H), 6.81 (s, 2H), 3.51-3.39 (m, 2H), 2.89 (dd, 1H), 2.82-2.71 (m, 1H), 2.50-2.35 (m, 1H), 2.24-2.06 (m, 4H), 2.04-1.95 (m, 6H), 1.68 (tdd, 1H) A62 1H NMR (400 MHz, d4-methanol) 7.82 (d, 1H), 7.77-7.69 (m, 1H), 7.68-7.60 (m, 1H), 6.87-6.78 (m, 2H), 3.49-3.39 (m, 2H), 2.88 (dd, 1H), 2.82-2.70 (m, 1H), 2.43 (dd, 1H), 2.24-2.06 (m, 4H), 2.02 (s, 6H), 1.75- 1.60 (m, 1H) A63 1H NMR (400 MHz, d4-methanol) 7.79 (dd, 1H), 7.41-7.33 (m, 2H), 6.83 (s, 2H), 3.48-3.38 (m, 2H), 2.88 (dd, 1H), 2.79- 2.72 (m, 1H), 2.43 (dd, 1H), 2.21 (s, 3H), 2.18-2.07 (m, 1H), 2.02 (s, 6H), 1.67 (td, 1H) A64 1H NMR (400 MHz, d4-methanol) 7.28 (d, 2H), 6.90 (s, 2H), 3.58-3.48 (m, 2H), 3.02-2.88 (m, 1H), 2.87-2.76 (m, 1H), 2.51 (dd, 1H), 2.33- 2.24 (m, 3H), 2.22- 2.12 (m, 1H), 2.08 (s, 6H), 1.82-1.66 (m, 1H) A65 1H NMR (400 MHz, d4-methanol) 7.64 (d, 1H), 7.44 (d, 1H), 6.82 (s, 2H), 3.47- 3.38 (m, 2H), 2.95- 2.81 (m, 1H), 2.80- 2.70 (m, 1H), 2.42 (dd, 1H), 2.21 (s, 3H), 2.17-2.06 (m, 1H), 2.05-1.95 (m, 6H), 1.67 (tdd, 1H) A66 1H NMR (400 MHz, d4-methanol) 8.19 (s, 1H), 8.12 (d, 1H), 7.86 (d, 1H), 7.66 (t, 1H), 6.81 (s, 2H), 3.52-3.42 (m, 2H), 2.89 (dd, 1H), 2.83- 2.71 (m, 1H), 2.44 (dd, 1H), 2.20 (s, 4H), 2.00 (s, 6H), 1.69 (tdd, 1H) A67 00 1H NMR (400 MHz, d4-methanol) 7.84 (dd, 1H), 7.80-7.74 (m, 1H), 7.70-7.64 (m, 1H), 6.89 (s, 2H), 3.53 (t, 2H), 2.96 (dd, 1H), 2.89-2.77 (m, 1H), 2.51 (dd, 1H), 2.28 (s, 3H), 2.25-2.13 (m, 1H), 2.08 (s, 6H), 1.75 (tdd, 1H) A68 01 1H NMR (400 MHz, d4-methanol) 7.61 (dd, 1H), 7.54 (dd, 1H), 7.41 (dt, 1H), 6.83 (s, 2H), 3.47- 3.39 (m, 2H), 2.94- 2.82 (m, 1H), 2.80- 2.69 (m, 1H), 2.47- 2.36 (m, 1H), 2.21 (s, 3H), 2.18-2.07 (m, 1H), 2.02 (s, 6H), 1.67 (tdd, 1H) A69 02 1H NMR (400 MHz, d4-methanol) 7.97- 7.85 (m, 1H), 7.71- 7.60 (m, 2H), 6.90 (s, 2H), 3.59-3.49 (m, 2H), 3.03-2.90 (m, 1H), 2.85 (d, 1H), 2.56-2.45 (m, 1H), 2.31-2.14 (m, 4H), 2.12-2.03 (m, 6H), 1.76 (tdd, 1H) A70 03 1H NMR (400 MHz, d4-methanol) 8.10- 7.98 (m, 2H), 7.43 (d, 2H), 6.89 (s, 2H), 3.58-3.49 (m, 2H), 2.96 (dd, 1H), 2.89- 2.78 (m, 1H), 2.51 (dd, 1H), 2.31-2.13 (m, 4H), 2.11-2.01 (m, 6H), 1.75 (tdd, 1H) A71 04 1H NMR (400 MHz, d4-methanol) 8.13- 8.02 (m, 2H), 7.83 (d, 2H), 6.88 (s, 2H), 3.54 (t,, 2H), 2.96 (dd, 1H), 2.88-2.78 (m, 1H), 2.51 (dd, 1H), 2.32-2.15 (m, 4H), 2.12-1.99 (m, 6H), 1.76 (tdd, 1H) A72 05 1H NMR (400 MHz, d4-methanol) 7.99- 7.87 (m, 2H), 7.34 (t, 2H), 6.92-6.83 (m, 2H), 3.09-2.99 (m, 2H), 2.93-2.83 (m, 1H), 2.84-2.67 (m, 1H), 2.60 (dd, 0.3H), 2.43-2.32 (m, 0.7H), 2.27 (s, 3H), 2.10-1.96 (m, 7H), 1.69-1.52 (m, 1H) A73 06 1H NMR (400 MHz, d4-methanol) 8.05 (d, 2H), 7.89 (d, 2H), 6.84 (br. s., 2H), 3.04 (t, 2H), 2.88- 2.66 (m, 2H), 2.30 (dd, 1H), 2.23 (s, 3H), 2.07-1.90 (m, 7H), 1.58 (qd, 1H) A74 07 1H NMR (400 MHz, d4-methanol) 7.98 (dd, 1H), 7.83 (ddd, 1H), 7.46 (t, 1H), 6.84 (s, 2H), 3.02 (t, 2H), 2.88-2.67 (m, 2H), 2.31 (dd, 1H), 2.23 (s, 3H), 2.08- 1.94 (m, 7H), 1.57 (tdd, 1H) A75 08 1H NMR (400 MHz, d4-methanol) 7.92- 7.82 (m, 1H), 7.71- 7.61 (m, 1H), 7.40- 7.27 (m, 2H), 6.84 (br. s., 2H), 3.14- 3.03 (m, 2H), 2.89- 2.69 (m, 2H), 2.37- 2.26 (m, 1H), 2.23 (s, 3H), 2.06-1.93 (m, 7H), 1.65-1.49 (m, 1H) A76 09 1H NMR (400 MHz, d4-methanol) 6.94- 6.85 (m, 2H), 3.30- 3.22 (m, 2H), 3.01- 2.92 (m, 1H), 2.91- 2.82 (m, 1H), 2.45 (dd, 1H), 2.31-2.25 (m, 3H), 2.21-2.10 (m, 1H), 2.09-2.04 (m, 6H), 1.74-1.57 (m, 1H), 1.37 (d, 6H), 1.20 (t, 1H) A77 0 1H NMR (400 MHz, d4-methanol) 8.03- 7.94 (m, 1H), 7.80- 7.70 (m, 2H), 6.88- 6.80 (m, 2H), 3.07- 2.97 (m, 2H), 2.91- 2.64 (m, 2H), 2.58 (dd, 0.4H), 2.35 (dd, 0.6H), 2.23 (d, 3H), 2.07-1.93 (m, 7H), 1.65-1.49 (m, 1H) A78 1H NMR (400 MHz, d4-methanol) 7.87- 7.75 (m, 2H), 7.14- 7.06 (m, 2H), 6.92- 6.82 (m, 2H), 3.90 (s, 3H), 3.04-2.96 (m, 2H), 2.91-2.74 (m, 2H), 2.35 (dd, 1H), 2.27 (s, 3H), 2.09-1.96 (m, 7H), 1.65-1.51 (m, 1H) A79 1H NMR (400 MHz, d4-methanol) 8.12- 8.02 (m, 1H), 7.64- 7.56 (m, 2H), 7.53- 7.44 (m, 1H), 6.85 (br. s., 2H), 3.09- 3.01 (m, 2H), 2.86- 2.70 (m, 2H), 2.33- 2.25 (m, 1H), 2.24 (s, 3H), 2.08-1.92 (m, 7H), 1.55 (dd, 1H) A80 1H NMR (400 MHz, d4-methanol) 7.89- 7.78 (m, 2H), 7.63- 7.53 (m, 2H), 6.90- 6.79 (m, 2H), 3.01 (t, 2H), 2.90-2.79 (m, 1H), 2.79-2.69 (m, 1H), 2.33 (dd, 1H), 2.24 (s, 3H), 2.06-1.93 (m, 7H), 1.57 (tdd, 1H) A81 1H NMR (400 MHz, d4-methanol) 7.81- 7.73 (m, 1H), 7.63- 7.56 (m, 1H), 7.18- 7.11 (m, 1H), 6.85 (s, 2H), 3.12-3.02 (m, 2H), 2.90-2.72 (m, 2H), 2.40-2.30 (m, 1H), 2.24 (s, 3H), 2.11-1.96 (m, 7H), 1.60 (tdd, 1H) A82 1H NMR (400 MHz, d4-methanol) 6.93- 6.86 (m, 2H), 3.28- 3.20 (m, 2H), 3.09 (q, 2H), 3.00-2.91 (m, 1H), 2.91-2.83 (m, 1H), 2.46 (dd, 1H), 2.28 (s, 3H), 2.22-2.11 (m, 1H), 2.10-2.04 (m, 6H), 1.74-1.59 (m, 1H), 1.35 (t, 3H) A83 1H NMR (400 MHz, d4-methanol) 8.04- 7.95 (m, 1H), 7.65 (d, 1H), 7.47 (dd, 1H), 6.84-6.75 (m, 2H), 3.08-2.98 (m, 2H), 2.85-2.58 (m, 2H), 2.49 (dd, 0.2H), 2.28 (dd, 0.8H), 2.19 (s, 3H), 2.04-1.88 (m, 7H), 1.60-1.44 (m, 1H) A84 1H NMR (400 MHz, d4-methanol) 8.00- 7.92 (m, 2H), 7.48 (d, 2H), 6.89-6.79 (m, 2H), 3.07-2.99 (m, 2H), 2.89-2.65 (m, 2H), 2.57 (dd, 0.4H), 2.34 (dd, 0.6H), 2.24 (s, 3H), 2.07-1.93 (m, 7H), 1.66-1.50 (m, 1H) A85 1H NMR (400 MHz, d4-methanol) 8.21- 8.13 (m, 1H), 7.94 (s, 1H), 7.80 (d, 2H), 6.85 (s, 2H), 3.12 (t, 2H), 2.90-2.80 (m, 1H), 2.80-2.71 (m, 1H), 2.34 (dd, 1H), 2.24 (s, 3H), 2.11- 2.00 (m, 4H), 1.97 (s, 3H), 1.59 (tdd, 1H) A86 1H NMR (400 MHz, d4-methanol) 7.95 (dd, 1H), 7.57-7.48 (m, 1H), 7.44-7.34 (m, 2H), 6.93-6.82 (m, 2H), 3.10-3.00 (m, 2H), 2.88-2.72 (m, 2H), 2.71-2.63 (m, 3H), 2.59-2.47 (m, 0.3H), 2.32 (dd, 0.7H), 2.27 (s, 3H), 2.10-1.95 (m, 7H), 1.64-1.49 (m, 1H) A87 0 1H NMR (400 MHz, d4-methanol) 7.51- 7.30 (m, 4H), 6.83 (s, 2H), 3.50-3.38 (m, 2H), 2.94-2.83 (m, 1H), 2.77 (dd, 1H), 2.50-2.36 (m, 1H), 2.26-2.18 (m, 3H), 2.18-2.07 (m, 1H), 2.05-1.97 (m, 6H), 1.68 (tdd, 1H) A88 1H NMR (400 MHz, CD3OD) 7.50- 7.71 (m, 4H) 6.85 (s, 2H) 3.65-3.79 (m, 2H) 2.88-2.99 (m, 1H) 2.71-2.83 (m, 1H) 2.56 (d, 1H) 2.24 (s, 3H) 1.98-2.20 (m, 8H) 1.68-1.81 (m, 1H) A89 1H NMR (400 MHz, CD3OD) 7.26- 7.43 (m, 2H) 7.03- 7.14 (m, 2H) 6.86 (s, 2H) 3.66-3.78 (m, 2H) 2.94 (dd, 1H) 2.76 (d, 1H) 2.55 (dd, 1H) 2.24 (s, 3H) 1.98-2.17 (m, 8H) 1.68-1.81 (m, 1H) A90 1H NMR (400 MHz, CD3OD) 7.29- 7.42 (m, 3H) 7.14- 7.23 (m, 2H) 6.86 (s, 2H) 3.66-3.80 (m, 2H) 2.88-2.99 (m, 1H) 2.70-2.82 (m, 1H) 2.56 (d, 1H) 2.24 (s, 3H) 1.99-2.20 (m, 7H) 1.68-1.81 (m, 1H) A91 1H NMR (400 MHz, CD3OD) 7.87- 7.94 (m, 2H) 7.58- 7.67 (m, 1H) 7.47- 7.55 (m, 2H) 6.86 (s, 2H) 3.81-3.96 (m, 2H) 2.95 (dd, 1H) 2.83 (brs, 1H) 2.57 (dd, 1H) 2.20- 2.32 (m, 4H) 1.99- 2.08 (m, 7H) 1.81- 1.94 (m, 1H) A92 1HNMR (400 MHz, CD3OD) 8.30-8.19 (m, 2H), 7.39 (t, 1H), 7.33- 7.25 (m, 1H), 7.10- 7.01 (m, 2H), 3.36 (dd, 1H), 2.98 (dd, 1H), 2.81 (br.s., 1H), 2.55-2.42 (m, 1H), 2.15-2.08 (m, 2H), 2.08-2.03 (m, 6H), 2.00 (s, 3H), 1.73 (br.s., 1H) A93 1HNMR (400 MHz, CD3OD) 8.32-8.22 (m, 2H), 7.46-7.26 (m, 1H), 6.92-6.81 (m, 2H), 3.49 (t, 2H), 2.99 (dd, 1H), 2.88-2.79 (m, 1H), 2.51 (dd, 1H), 2.29-2.23 (m, 3H), 2.22-2.11 (m, 1H), 2.08-2.03 (m, 6H), 1.79-1.70 (m, 1H) A94 1HNMR (400 MHz, CD3OD) 6.88 (s, 2H), 3.51- 3.33 (m, 2H), 2.98 (dd, 1H), 2.84-2.75 (m, 4H), 2.49-2.39 (m, 1H), 2.27-2.22 (m, 3H), 2.10-1.98 (m, 7H), 1.80-1.70 (m, 1H) A95 1HNMR (400 MHz, CD3OD) 9.07-8.94 (m, 1H), 8.64-8.54 (m, 1H), 8.35-8.02 (m, 1H), 6.91-6.82 (m, 2H), 3.51-3.40 (m, 2H), 3.01-2.90 (m, 1H), 2.81 (dddd, 1H), 2.55-2.43 (m, 1H), 2.29-2.22 (m, 3H), 2.21-2.08 (m, 1H), 2.07-1.98 (m, 6H), 1.72 (tdd, 1H) A96 1H NMR (400 MHz, CD3OD) = 8.91 (d, 1H), 8.21 (d, 1H), 6.92-6.81 (m, 2H), 6.68 (d, 1H), 3.64 (d, 2H), 2.95 (dd, 1H), 2.84 (br. s., 1H), 2.56- 2.39 (m, 1H), 2.30- 2.22 (m, 3H), 2.22-2.10 (m, 1H), 2.09- 2.00 (m, 6H), 1.89- 1.67 (m, 1H) A97 0 1HNMR (400 MHz, CD3OD) 8.16 (s, 1H), 7.99 (d, 1H), 6.88 (s, 2H), 3.82 (td, 1H), 3.69 (td, 1H), 3.03 (dd, 1H), 2.92-2.81 (m, 1H), 2.50 (dd, 1H), 2.26 (s, 3H), 2.20-2.12 (m, 1H), 2.10-2.01 (m, 6H), 2.01-1.89 (m, 1H) A98 1HNMR (400 MHz, CD3OD) 8.34 (s, 1H), 8.17 (s, 1H), 8.06 (dd, 1H), 7.67 (s, 1H), 7.50-7.41 (m, 2H), 3.85 (td, 1H), 3.72 (td, 1H), 3.14-3.04 (m, 1H), 2.98-2.86 (m, 1H), 2.56 (dd, 1H), 2.24-2.15 (m, 7H), 2.07-1.94 (m, 1H) A99 1HNMR (400 MHz, CD3OD) 9.11 (d, 1H), 8.31 (s, 1H), 8.22 (dd, 1H), 7.66-7.59 (m, 1H), 7.45-7.32 (m, 2H), 6.60-6.49 (m, 1H), 4.37-4.17 (m, 2H), 2.99-2.85 (m, 1H), 2.81-2.71 (m, 1H), 2.51 (dd, 1H), 2.37-2.27 (m, 1H), 2.20-2.13 (m, 6H), 1.98-1.87 (m, 1H) A100 1HNMR (400 MHz, CD3OD14ax426h 1) 8.32 (s, 1H), 8.27-8.13 (m, 1H), 7.72-7.65 (m, 1H), 7.60 (dd, 1H), 7.45-7.37 (m, 2H), 6.69-6.48 (m, 1H), 3.71-3.44 (m, 2H), 3.03-2.84 (m, 2H), 2.49 (dd, 1H), 2.21-2.08 (m, 7H), 1.88-1.71 (m, 1H) A101 1HNMR (400 MHz, CDCl3) 8.26 (d, 2H), 7.57 (d, 1H), 7.41 (t, 1H), 6.89 (s, 2H), 3.22- 2.98 (m, 5H), 2.83 (d, 1H), 2.48 (d, 1H), 2.32-2.23 (m, 4H), 2.13 (d, 8H), A102 1H NMR (400 MHz, Methanol) = 6.95- 6.77 (m, 2H), 3.55-3.37 (m, 2H), 2.98 (s, 2H), 2.95-2.85 (m, 1H), 2.84- 2.67 (m, 1H), 2.55- 2.38 (m, 1H), 2.25 (s, 3H), 2.20-2.08 (m, 1H), 2.04 (d, J = 2.2 Hz, 6H), 1.77-1.57 (m, 1H), 1.41 (s, 6H) A103 1H NMR (400 MHz, Methanol) = 6.95- 6.77 (m, 2H), 3.55-3.37 (m, 2H), 2.98 (s, 2H), 2.95-2.85 (m, 1H), 2.84- 2.67 (m, 1H), 2.55- 2.38 (m, 1H), 2.25 (s, 3H), 2.20-2.08 (m, 1H), 2.04 (d, J = 2.2 Hz, 6H), 1.77-1.57 (m, 1H), 1.41 (s, 6H) A104 1H NMR (400 MHz,CD3OD) = 8.33 (d, J = 2.6 Hz, 1H), 8.28 (dd, J = 2.7, 9.3 Hz, 1H), 7.00 (d, J = 9.4 Hz, 1H), 6.87 (s, 2H), 3.66-3.48 (m, 2H), 2.94 (dd, J = 7.0, 17.9 Hz, 1H), 2.82 (br. s., 1H), 2.45 (dd, J = 2.3, 17.9 Hz, 1H), 2.29- 2.22 (m, 3H), 2.22- 2.14 (m, 1H), 2.06- 2.00 (m, 6H), 1.88-1.75 (m, 1H) A105 1HNMR (400 MHz, CD3OD) 8.07-7.99 (m, 2H), 6.87 (s, 2H), 6.69- 6.60 (m, 2H), 3.42- 3.35 (m, 2H), 2.95- 2.81 (m, 2H), 2.46 (dd, 1H), 2.25 (s, 3H), 2.24-2.16 (m, 1H), 2.05 (s, 6H), 1.84-1.73 (m, 1H) A106 1HNMR (400 MHz, CD3OD) 7.75 (d, 1H), 7.71- 7.60 (m, 1H), 6.98 (d, 1H), 6.87 (s, 2H), 3.56-3.40 (m, 2H), 2.93 (dd, 1H), 2.85-2.75 (m, 1H), 2.44 (dd, 1H), 2.25 (s, 3H), 2.20-2.10 (m, 1H), 2.05 (d, 6H), 1.87-1.71 (m, 1H) A107 0 1HNMR (400 MHz, CD3OD) 8.31 (d, 1H), 7.58 (dd, 1H), 6.86 (s, 2H), 6.55 (d, 1H), 3.62-3.47 (m, 2H), 2.95-2.76 (m, 2H), 2.46 (d, 1H), 2.25 (s, 3H), 2.21-2.12 (m, 1H), 2.06-2.03 (m, 6H), 1.80-1.64 (m, 1H) A108 1HNMR (400 MHz, CDCl3) 7.41-7.28 (m, 1H), 7.04 (s, 2H), 3.66- 3.46 (m, 1H), 3.42- 3.28 (m, 1H), 2.97- 2.96 (m, 1H), 2.94 (s, 2H), 2.85-2.64 (m, 2H), 2.28-2.13 (m, 1H), 2.12-1.66 (m, 10H), 1.44 (d, 6H) A109 1HNMR (400 MHz, CDCl3) 7.57-7.42 (m, 2H), 7.23 (s, 2H), 7.09 (s, 2H), 3.58-3.44 (m, 2H), 2.98 (s, 2H), 2.95-2.85 (m, 1H), 2.83-2.71 (m, 1H), 2.48-2.32 (m, 1H), 2.17 (d, 7H), 1.86-1.66 (m, 1H), 1.45 (s, 6H) A110 1HNMR (400 MHz, CDCl3) 8.58 (s, 2H), 7.93 (s, 2H), 7.50-7.30 (m, 1H), 3.62-3.26 (m, 2H), 2.94 (s, 2H), 2.85-2.63 (m, 2H), 2.11 (d, 7H), 1.99- 1.85 (m, 1H), 1.80- 1.61 (m, 1H), 1.49- 1.36 (m, 6H) A111 1HNMR (400 MHz, CDCl3) 8.32 (d, 1H), 7.56-6.89 (m, 4H), 3.65-3.24 (m, 2H), 2.95 (s, 2H), .85-2.6, (m, 2H), 22.11 (d, 7H), 2.00-1.85 (m, 1H), 1.82-1.65 (m, 1H), 1.53-1.36 (m, 6H) A112 1HNMR (400 MHz, CD3OD) 8.31 (dd, 1H), 7.58 (dd, 1H), 7.09-7.01 (m, 2H), 6.55 (dd, 1H), 3.61-3.47 (m, 2H), 2.95-2.87 (m, 1H), 2.81 (br.s., 1H), 2.52-2.39 (m, 1H), 2.25-2.11 (m, 1H), 2.05 (d, 6H), 2.01-1.98 (m, 3H), 1.79-1.63 (m, 1H) A113 1HNMR (400 MHz, CD3OD) 8.24-8.15 (m, 1H), 7.60 (dd, 1H), 7.10-6.98 (m, 2H), 6.61 (d, 1H), 3.65- 3.42 (m, 2H), 2.98- 2.79 (m, 2H), 2.46 (dd, 1H), 2.22-2.09 (m, 1H), 2.08-2.03 (m, 6H), 1.99-1.96 (m, 3H), 1.85-1.57 (m, 1H) A114 1HNMR (400 MHz, CDCl3) 8.93 (s, 2H), 8.05 (s, 2H), 7.40-7.30 (m, 1H), 3.67-3.46 (m, 1H), 3.46-3.22 (m, 1H), 2.97 (s, 2H), 2.91-2.62 (m, 3H), 2.15 (d, 7H), 2.0- 1.90 (m, 1H), 1.44 (d, 6H) A115 1HNMR (400 MHz, CDCl3) 7.35 (s, 1H), 6.62 (s, 2H), 4.36-4.22 (m, 2H), 3.71-3.49 (m, 1H), 3.45-3.29 (m, 1H), 2.95 (s, 2H), 2.81 (d, 2H), 2.23 (d, 1H), 2.06 (s, 6H), 1.99-1.74 (m, 2H), 1.44 (d, 6H) A116 1HNMR (400 MHz, CDCl3) 8.80 (s, 2H), 8.10 (s, 2H), 4.09-3.88 (m, 1H), 3.44-3.23 (m, 1H), 3.01 (s, 4H), 2.26 (d, 7H), 1.96- 1.78 (m, 1H), 1.49 (d, 7H) A117 0 1HNMR (400 MHz, CDCl3) 8.36 (d, 1H), 7.55-7.13 (m, 4H), 3.64-3.26 (m, 2H), 2.95 (s, 2H), 2.85-2.65 (m, 2H), 2.30-2.04 (m, 7H), 2.01-1.87 (m, 1H), 1.84-1.65 (m, 1H), 1.52-1.35 (m, 6H) A118 1HNMR (400 MHz, CDCl3) 8.67 (s, 2H), 7.96 (br.s., 2H), 7.48-7.29 (m, 1H), 3.79-3.22 (m, 2H), 2.95 (s, 4H), 2.33-2.07 (m, 7H), 1.99-1.65 (m, 2H), 1.55-1.36 (m, 6H) A119 1HNMR (400 MHz, CDCl3) 8.98-8.84 (m, 1H), 8.04-7.91 (m, 1H), 7.88-7.78 (m, 1H), 7.76-7.67 (m, 2H), 4.08-3.93 (m, 1H), 3.43-3.24 (m, 1H), 3.13-2.88 (m, 4H), 2.27 (d, 7H), 1.95- 1.77 (m, 1H), 1.49 (d, 7H) A120 1HNMR (400 MHz, CD3OD) 8.80-8.69 (m, 2H), 8.29-8.17 (m, 1H), 8.13-8.02 (m, 2H), 7.60 (dd, 1H), 6.71-6.54 (m, 1H), 3.66-3.45 (m, 2H), 3.03-2.79 (m, 2H), 2.50 (dd, 1H), 2.25-2.11 (m, 7H), 1.85-1.73 (m, 1H) A121 1HNMR (400 MHz, CD3OD) 8.22 (s, 2H), 6.90- 6.64 (m, 2H), 3.57- 3.45 (m, 2H), 2.93- 2.75 (m, 2H), 2.52- 2.38 (m, 1H), 2.24 (s, 3H), 2.21-2.11 (m, 1H), 2.04 (s, 6H), 1.79-1.60 (m, 1H) A122 1HNMR (400 MHz, CD3OD) 7.26 (d, 1H), 7.02- 6.92 (m, 1H), 6.59- 6.42 (m, 1H), 5.60 (ddd, 1H), 5.15- 5.04 (m, 1H), 3.50- 3.37 (m, 2H), 3.01- 2.97 (m, 2H), 2.95- 2.71 (m, 2H), 2.47 (d, 1H), 2.33-2.26 (m, 3H), 2.21-2.08 (m, 1H), 2.05 (d, 3H), 1.72-1.60 (m, 1H), 1.46-1.39 (m, 6H) A123 1HNMR (400 MHz, CD3OD) 7.38 (s, 1H), 7.25 (s, 1H), 3.57-3.38 (m, 2H), 3.04-2.94 (m, 2H), 2.97-2.82 (m, 1H), 2.79-2.66 (m, 1H), 2.47 (s, 1H), 2.43 (br.s., 1H), 2.38 (s, 3H), 2.15 (s, 3H), 2.14- 2.05 (m, 1H), 1.81- 1.60 (m, 1H), 1.42 (d, 6H) A124 1HNMR (400 MHz, CD3OD) 8.25 (dd, 1H), 7.78 (dd, 1H), 6.86 (s, 2H), 6.64 (dd, 1H), 3.64 (t, 2H), 2.96- 2.86 (m, 1H), 2.79 (br.s., 1H), 2.48 (d, 1H), 2.24 (s, 3H), 2.22-2.14 (m, 1H), 2.05 (s, 6H), 1.80- 1.64 (m, 1H) A125 1HNMR (400 MHz, CD3OD) 8.26 (s, 2H), 6.88 (s, 2H), 3.59-3.49 (m, 2H), 2.97-2.88 (m, 1H), 2.85-2.74 (m, 1H), 2.49 (dd, 1H), 2.27 (s, 3H), 2.23-2.14 (m, 1H), 2.06 (d, 6H), 1.77- 1.64 (m, 1H) A126 1H NMR (400 MHz, CD3OD) = 8.30 (s, 2H), 6.92-6.74 (m, 2H), 3.56- 3.43 (m, 2H), 2.95- 2.85 (m, 1H), 2.79 (br. s., 1H), 2.46 (dd, J = 2.0, 17.7 Hz, 1H), 2.24 (s, 3H), 2.22-2.10 (m, 1H), 2.04 (d, J = 2.3 Hz, 6H), 1.76-1.63 (m, 1H)

BIOLOGICAL EXAMPLES

Biological Example 1

(132) Test-Glasshouse Assay for Herbicidal Activity

(133) Seeds of a variety of monocotyledonous and dicotyledonous test plants are sown in standard soil in pots. The plants are cultivated for one day (for pre-emergence) or for about 12 days (for post-emergence) under controlled conditions in a glasshouse (warm climate species at 24/18 C., cool climate species at 20/16 C., both at day/night; 16 hours light; 65% humidity).

(134) The test plants are then grown on, in a glasshouse (greenhouse) under controlled conditions (warm climate species at 24/18 C., cool climate species at 20/16 C., both at day/night; 16 hours light; 65% humidity) and are watered twice daily. 15 days after application of the test herbicide (15DAA) (for post-emergence), and 20 days after application of the test herbicide (20DAA) (for pre-emergence), the test plants are evaluated visually, and an assessed percentage phytotoxicity score is given for each herbicidal application on each plant species (with 100%=total damage to plant; 0%=no damage to plant).

(135) The plant species tested are as follows: Alopecurus myosuroides (ALOMY), Avena fatua (AVEFA), Lolium perenne (LOLPE), Echinochloa crus-galli (ECHCG).

(136) TABLE-US-00011 TABLE 1 Pre-/Post- emergence herbicidal activity (percentage phytotoxicity). Rate LOLPE ALOMY ECHCG AVEFA Compound g/ha PRE POST PRE POST PRE POST PRE POST A1 250 100 90 80 90 100 80 60 90 A2 250 80 100 70 80 90 100 80 100 A3 250 90 100 100 100 100 100 80 90 A4 250 80 100 80 90 60 90 70 100 A5 250 90 90 100 80 90 100 80 90 A6 250 80 90 30 70 90 100 0 90 A7 250 0 70 0 10 0 90 0 90 A8 250 90 90 70 80 90 80 90 90 A9 250 80 90 60 30 80 80 60 80 A10 250 0 90 0 80 0 90 0 80 A11 250 100 100 100 90 100 90 90 90 A12 250 90 90 90 90 100 90 90 90 A13 250 50 70 70 90 90 100 40 100 A14 250 100 100 90 80 100 100 90 90 A15 250 70 70 70 60 70 30 50 50 A16 250 90 90 80 90 100 80 70 100 A17 250 30 40 40 70 10 70 0 70 A18 250 70 80 60 80 60 90 50 80 A19 250 80 100 70 90 80 100 90 100 A20 250 80 90 20 80 100 100 80 100 A21 250 80 90 90 90 100 100 90 100 A22 250 100 90 70 80 100 100 100 100 A23 250 100 90 100 90 100 100 100 100 A24 250 80 90 10 60 90 100 70 100 A25 250 30 20 30 70 50 90 0 80 A26 250 0 40 0 10 0 10 0 0 A27 250 90 100 60 90 90 100 90 90 A28 250 70 80 70 90 90 90 70 100 A29 250 100 100 90 100 90 100 100 100 A30 250 90 80 80 90 60 90 80 80 A31 250 100 90 80 90 90 70 70 90 A32 250 60 60 70 80 80 100 50 100 A33 250 0 30 60 40 70 80 40 40 A34 250 100 90 90 90 100 100 80 90 A35 250 100 100 70 90 80 100 60 70 A36 250 90 100 60 90 90 90 90 100 A37 250 0 0 0 0 0 30 0 0 A38 250 70 80 70 70 100 100 70 80 A39 250 90 100 80 80 30 50 50 80 A40 250 100 90 90 100 100 100 100 100 A41 250 0 40 0 60 0 60 0 20 A42 250 0 10 0 0 0 70 0 0 A43 250 90 100 90 90 90 100 90 100 A44 250 10 0 0 0 0 70 0 0 A45 250 90 80 0 20 80 40 0 0 A46 250 70 100 30 70 60 100 30 90 A47 250 50 30 60 60 80 60 0 70 A48 250 100 100 100 90 90 100 90 100 A49 250 90 100 90 100 100 100 80 100 A50 250 90 100 100 100 90 80 80 90 A51 250 60 90 70 90 90 90 30 80 A52 250 80 90 80 90 100 90 70 80 A53 250 90 100 80 90 100 100 70 100 A54 250 80 100 60 100 80 100 60 100 A55 250 70 90 60 70 80 80 10 0 A56 250 80 90 70 80 60 80 40 80 A57 250 70 100 80 90 100 80 0 50 A58 250 0 90 0 40 0 80 0 10 A59 250 80 100 70 90 100 90 30 90 A60 250 80 90 70 100 70 80 80 100 A61 250 40 70 20 40 30 70 30 0 A62 250 40 80 70 90 80 80 30 80 A63 250 80 90 90 100 70 80 40 90 A64 250 80 100 100 90 80 90 80 90 A65 250 80 100 80 100 70 80 70 90 A66 250 40 80 20 70 10 60 0 30 A67 250 20 NT 0 NT 30 NT 0 NT A68 250 30 80 0 50 10 70 10 0 A69 250 80 100 80 100 70 70 80 90 A70 250 60 100 50 20 100 90 40 90 A71 250 40 80 30 20 0 80 20 50 A72 250 10 80 20 30 0 80 20 90 A73 250 70 60 70 40 30 30 0 60 A74 250 70 60 70 50 70 60 90 NC A75 250 80 70 70 60 70 30 60 80 A76 250 70 60 30 20 40 40 0 20 A77 250 80 80 100 80 70 70 70 80 A78 250 70 60 60 40 20 30 0 80 A79 250 70 60 30 30 50 40 10 60 A80 250 60 60 10 10 40 0 0 0 A81 250 70 60 60 60 70 60 70 70 A82 250 70 50 70 40 30 20 0 30 A83 250 90 70 90 80 70 70 80 80 A84 250 50 70 50 30 30 50 10 80 A85 250 80 50 70 60 70 40 80 80 A86 250 60 30 20 50 60 30 20 0 A87 250 70 0 0 0 30 0 0 50 A88 250 40 60 0 0 40 0 0 0 A89 250 40 0 0 0 30 0 0 40 A90 250 70 20 0 20 40 60 0 60 A91 250 70 70 60 80 70 0 60 10 A92 250 70 100 70 90 80 100 30 100 A93 250 90 70 90 90 90 100 70 90 A94 250 100 80 80 60 70 90 60 90 A95 250 70 60 80 70 70 70 20 70 A96 250 100 100 80 90 100 100 90 100 A97 250 100 90 80 90 90 100 90 90 A98 250 90 90 40 90 90 100 70 100 A99 250 0 60 0 70 0 100 0 90 A100 250 70 100 60 90 90 100 50 100 A101 250 30 40 40 70 10 70 0 70 A102 250 100 100 100 100 100 100 90 100 A103 250 80 70 80 80 60 70 50 80 A104 250 80 90 60 90 90 70 70 80 A105 250 20 80 20 90 10 90 20 80 A106 250 60 90 70 90 90 90 40 90 A107 250 100 100 90 100 100 100 90 100 A108 250 100 100 100 100 100 100 90 100 A109 250 90 100 90 100 90 100 90 100 A110 250 90 90 100 100 90 100 90 100 A111 250 90 40 100 100 90 100 100 100 A112 250 90 100 100 100 100 100 90 100 A113 250 90 100 90 100 90 100 70 100 A114 250 70 100 90 90 70 100 80 100 A115 250 90 90 100 100 70 100 80 100 A116 250 90 100 90 100 90 100 90 100 A117 250 80 100 90 100 80 100 80 100 A118 250 90 100 100 100 90 100 90 100 A119 250 80 100 90 90 90 100 80 100 A120 250 90 90 90 90 90 100 90 100 A121 250 100 90 100 100 100 100 100 100 A122 250 0 80 0 90 0 90 0 90 A123 250 90 80 70 100 20 100 50 100 A124 250 80 80 60 80 90 100 40 60 A125 250 90 100 90 90 90 100 80 90 A126 250 90 90 80 90 80 90 100 90 NT = not tested.

(137) TABLE-US-00012 TABLE 2 Post-emergence herbicidal activity against cereal crops (wheat) +/ safener (cloquintocet-mexyl (CQC) applied at 50 g/ha) - Results (percentage phytotoxicity) Post-emergence Crop Selectivity Compound Rate (g/ha) Wheat CQC +CQC A1 250 80 20 A2 250 80 80 A3 250 90 60 A4 250 90 50 A5 250 50 20 A6 250 10 10 A7 250 20 0 A8 250 70 10 A9 250 40 10 A10 250 70 20 A11 250 80 70 A12 250 90 80 A13 250 70 40 A14 250 60 30 A15 250 40 30 A16 250 80 50 A17 250 50 10 A18 250 60 0 A19 250 80 80 A20 250 80 0 A21 250 90 70 A22 250 80 30 A23 250 90 80 A24 250 80 70 A25 250 60 0 A26 250 0 10 A27 250 80 70 A28 250 80 20 A29 250 90 70 A30 250 70 40 A31 250 70 10 A32 250 60 10 A33 250 40 10 A34 250 80 70 A35 250 80 60 A36 250 80 10 A37 250 20 10 A38 250 70 30 A39 250 60 10 A40 250 90 80 A41 250 60 20 A42 250 0 10 A43 250 90 50 A44 250 30 10 A45 250 0 0 A46 250 80 70 A47 250 50 0 A48 250 60 50 A49 250 90 90 A50 250 90 90 A51 250 80 80 A52 250 80 30 A53 250 90 80 A54 250 90 80 A55 250 30 0 A56 250 80 70 A57 250 80 20 A58 250 80 20 A59 250 90 80 A60 250 80 70 A61 250 70 40 A62 250 80 70 A63 250 80 80 A64 250 90 80 A65 250 80 40 A66 250 80 40 A67 250 0 0 A68 250 90 0 A69 250 90 80 A70 250 80 80 A71 250 80 20 A72 250 80 70 A73 250 0 10 A74 250 10 0 A75 250 0 0 A76 250 0 0 A77 250 80 10 A78 250 0 0 A79 250 30 0 A80 250 0 0 A81 250 0 0 A82 250 0 0 A83 250 80 10 A84 250 0 0 A85 250 20 10 A86 250 20 0 A87 250 20 0 A88 250 0 0 A89 250 10 0 A90 250 0 20 A91 250 70 70