Herbicidally active 2-(substituted-phenyl)-cyclopentane-1,3-dione compounds and derivatives thereof

Abstract

The present invention relates to a compound of formula (I): wherein the substituents 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): ##STR00362## wherein: R.sup.1 is methyl, ethyl, n-propyl, cyclopropyl, trifluoromethyl, vinyl, ethynyl, fluorine,chlorine, bromine, methoxy, ethoxy or fluoromethoxy; R.sup.2 is 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, or (C.sub.1-C.sub.2 fluoroalkyl)-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; or R.sup.2 is ##STR00363##  in which R.sup.36 is fluorine or chlorine, and R.sup.37 is fluorine, chlorine or C.sub.1fluoroalkyl; and R.sup.3 is 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-, or C.sub.1fluoroalkoxy-C.sub.1-C.sub.3alkoxy-; R.sup.4, R.sup.5 and R.sup.6, independently of each other, are hydrogen, C.sub.1-C.sub.5alkyl, C.sub.2-C.sub.3alkenyl, C.sub.2-C.sub.3alkynyl, C.sub.1-C.sub.2fluoroalkyl or C.sub.1-C.sub.2alkoxyC.sub.1-C.sub.2alkyl; provided that: either (i) at least two of R.sup.4, R.sup.5 and R.sup.6 are hydrogen, or (ii) two of R.sup.4, R.sup.5 and R.sup.6 are methyl and the remaining one of R.sup.4, R.sup.5 and R.sup.6 is hydrogen; and R.sup.7 and R.sup.8, independently of each other, are hydrogen, fluorine or C.sub.1-C.sub.3alkyl; and R.sup.9 and R.sup.10, independently of each other, are hydrogen, fluorine or C.sub.1-C.sub.3alkyl; provided that no more than two of R.sup.7, R.sup.8, R.sup.9 and R.sup.10 are fluorine; and provided that at least two of R.sup.7, R.sup.8, R.sup.9 and R.sup.10 are hydrogen; and wherein R.sup.11 is C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.7cycloalkyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, oxetanyl, tetrahydrothiophene-yl or thietanyl; or R.sup.11 is a monocyclic 6-membered-ring heteroaryl, which is carbon-linked, and which is pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl or 1,2,4-triazinyl, wherein the monocyclic 6-membered-ring heteroarylisoptionally substituted by 1, 2 or 3 substituents; wherein the 1, 2 or 3 optional substituents on the monocyclic 6-membered-ring heteroaryl independently are fluorine, chlorine, bromine, iodine, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoro alkyl, C.sub.1-C.sub.2alkoxy C.sub.1-C.sub.2fluoroalkoxy, cyclopropyl, C.sub.n1alkoxyC.sub.n2alkyl (wherein n1 is 1 or 2, n2 is 1 or 2, and n1+n2 is 2 or 3), vinyl, C.sub.2fluoroalkenyl, C.sub.2-C.sub.3alkynyl, fluoroethynyl, cyano, amino, or phenyl in which the phenyl is optionally substituted at its meta and/or para position(s) by 1 or 2 fluorines; and wherein, when R.sup.11 is pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl or 1,2,4-triazinyl, then each of these is optionally substituted by 1 or 2 of the substituents on the monocyclic 6-membered-ring heteroaryl, as defined herein; wherein, when R.sup.11 is pyridin-3-yl or pyridin-4-yl, then each of these is substituted by 1 or 2 of the substituents on the monocyclic 6-membered-ring heteroaryl, as defined herein, wherein, when R.sup.11 is pyridin-2-yl substituted by 3 substituents, then one or more of the optional substituents on the pyridin-2-yl is or are fluorine; wherein, when R.sup.11 is monocyclic 6-membered-ring heteroaryl substituted by C.sub.2alkyl, C.sub.2fluoroalkyl, C.sub.2alkoxy or C.sub.2fluoroalkoxy, then: the monocyclic 6-membered-ring heteroaryl is substituted by 1 or 2 substituents independently being C.sub.2alkyl, C.sub.2fluoroalkyl, C.sub.2alkoxy or C.sub.2fluoroalkoxy, and the monocyclic 6-membered-ring heteroaryl is optionally further substituted by 1 or 2 substituents independently being fluorine, chlorine, bromine, C.sub.1alkyl, C.sub.1fluoroalkyl, C.sub.1alkoxy, C.sub.1fluoroalkoxy or cyano; provided that the monocyclic 6-membered-ring heteroaryl is substituted by no more than 2 substituents or in the case of a pyridin-2-yl is substituted by no more than 3 substituents; wherein, when R.sup.11 is monocyclic 6-membered-ring heteroaryl substituted by iodine, C.sub.3alkyl, C.sub.3fluoroalkyl, cyclopropyl, C.sub.n1alkoxyC.sub.n2alkyl, vinyl, C.sub.2fluoroalkenyl, C.sub.2-C.sub.3alkynyl or fluoroethynyl, then: the monocyclic 6-membered-ring heteroaryl is pyridin-2-yl substituted by only one iodine, C.sub.3alkyl, C.sub.3fluoroalkyl, cyclopropyl, C.sub.n1alkoxyC.sub.n2alkyl, vinyl, C.sub.2fluoroalkenyl, C.sub.2-C.sub.3alkynyl or fluoroethynyl, and in which the pyridin-2-yl ring is optionally further substituted by 1 or 2 fluorines; wherein, when R.sup.11 is monocyclic 6-membered-ring heteroaryl substituted by amino, then: either the monocyclic 6-membered-ring heteroaryl is 6-amino-pyridin-2-yl optionally further substituted by 1 or 2 fluorines; or the monocyclic 6-membered-ring heteroaryl is 3-amino-pyridin-2-yl or 3-amino-pyrazin-2-yl each of which is optionally further substituted at the 5-position of the pyridin-2-yl or pyrazin-2-yl ring by hydrogen, fluorine, methyl or C.sub.1fluoroalkyl; and wherein, when R.sup.11 is monocyclic 6-membered-ring heteroaryl substituted by optionally substituted phenyl, then the monocyclic 6-membered-ring heteroaryl is 6-phenyl-pyridin-2-yl in which the phenyl is optionally substituted at its meta and/or para position(s) by 1 or 2 fluorines, and in which the pyridin-2-yl ring is optionally further substituted by 1 or 2 fluorines; or R.sup.11 is a monocyclic 5-membered-ring heteroaryl, which is carbon-linked, and which is pyrrolyl, pyrazolyl, imidazol-2-yl, triazolyl, tetrazolyl, furyl, thiophenyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, oxadiazolyl, or thiadiazolyl, wherein the monocyclic 5-membered-ring heteroaryl is optionally substituted by 1, 2 or 3 substituents; wherein the 1, 2 or 3 optional substituents on the monocyclic 5-membered-ring heteroaryl are: 1, 2 or 3 optional ring-carbon substituents independently being fluorine, chlorine, bromine, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.2alkoxy, C.sub.1-C.sub.2fluoroalkoxy, cyclopropyl, C.sub.n3alkoxyC.sub.n4alkyl (wherein n3 is 1 or 2, n4 is 1 or 2, and n3+n4 is 2 or 3), vinyl, C.sub.2fluoroalkenyl, C.sub.2-C.sub.3alkynyl, fluoroethynyl or cyano; and/or 1 substituent being C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl or cyclopropyl, substituted at a ring nitrogen not partaking in a double bond, when the monocyclic 5-membered-ring heteroaryl has a ring nitrogen not partaking in a double bond; provided that the monocyclic 5-membered-ring heteroaryl has no more than 3 substituents, or has no more than the maximum number of substituents possible for the monocyclic 5-membered-ring heteroaryl in uncharged form if this maximum is less than 3 substituents; and wherein, when R.sup.11 is a monocyclic 5-membered-ring heteroaryl having a ring nitrogen not partaking in a double bond, then the ring nitrogen not partaking in a double bond is substituted by C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl or cyclopropyl; and wherein, when R.sup.11 is a monocyclic 5-membered-ring heteroaryl, then: the monocyclic 5-membered-ring heteroaryl has no more than one C.sub.3fluoroalkyl, vinyl, C.sub.2fluoroalkenyl, C.sub.2-C.sub.3alkynyl or fluoroethynyl substituent; the monocyclic 5-membered-ring heteroaryl has no more than 2 substituents independently being bromine, C.sub.2-C.sub.3alkyl, C.sub.2-C.sub.3fluoroalkyl, C.sub.1-C.sub.2alkoxy, C.sub.1-C.sub.2fluoroalkoxy, cyclopropyl, C.sub.n3alkoxyC.sub.n4alkyl, vinyl, C.sub.2fluoroalkenyl, C.sub.2-C.sub.3alkynyl, fluoroethynyl or cyano; and the monocyclic 5-membered-ring heteroaryl has no more than 2 substituents independently being chlorine or bromine; or R.sup.11 is one of the following sub-formulae B, E, F, GG, H, J, Q, R, S, T or U: ##STR00364## ##STR00365## wherein: X.sup.B is nitrogen or CR.sup.13B; Y.sup.B is nitrogen or CR.sup.14B; Z.sup.B is nitrogen or CR.sup.15B; provided that no more than one of X.sup.B, Y.sup.B and Z.sup.B is nitrogen; and R.sup.12B is hydrogen, fluorine, chlorine or bromine; R.sup.13B is hydrogen, fluorine, chlorine, bromine, methyl, C.sub.1fluoroalkyl, cyano, methoxy or C.sub.1fluoroalkoxy; R.sup.14B is hydrogen, fluorine or chlorine; R.sup.15B is hydrogen, fluorine, chlorine or bromine; provided that at least two of R.sup.12B, R.sup.13B, R.sup.14B and R.sup.15B are hydrogen; and provided that, when R.sup.13B is bromine, then X.sup.A is CR.sup.13B, and R.sup.12B, R.sup.14B and R.sup.15B are independently hydrogen or fluorine, provided that at least two of R.sup.12B, R.sup.14B and R.sup.15B are hydrogen; and R.sup.15E is hydrogen, fluorine or chlorine; R.sup.12F is hydrogen, fluorine or chlorine; R.sup.11GG is hydrogen, fluorine, methyl or C.sub.1fluoroalkyl; R.sup.12GG is hydrogen, fluorine or chlorine; R.sup.13GG is hydrogen, fluorine, chlorine, bromine, C.sub.1fluoroalkyl, methoxy or C.sub.1fluoroalkoxy; R.sup.14GG is hydrogen or fluorine; R.sup.15GG is hydrogen, fluorine, chlorine, methoxy or C.sub.1fluoroalkoxy; provided that, when R.sup.13GG is bromine, then R.sup.11GG, R.sup.12GG, R.sup.14GG and R.sup.15GG are independently hydrogen or fluorine; provided that, when R.sup.11GG is methyl or C.sub.1fluoroalkyl, then R.sup.12GG, R.sup.13GG, R.sup.14GG and R.sup.15GG are independently hydrogen or fluorine; and provided that at least two of R.sup.12GG, R.sup.13GG, R.sup.14GG and R.sup.15GG are hydrogen; and R.sup.26 is hydrogen or methyl; R.sup.27 is hydrogen or methyl; R.sup.28 and R.sup.29 independently are hydrogen or fluorine; R.sup.12T, R.sup.13T and R.sup.14T are independently hydrogen or fluorine, provided that at least two of R.sup.12T, R.sup.13T and R.sup.14T are hydrogen; and R.sup.12U, R.sup.13U and R.sup.14U are independently hydrogen or fluorine, provided that at least two of R.sup.12U, R.sup.13U and R.sup.14U are hydrogen; 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.c—R.sup.b, —C(X.sup.d)—N(R.sup.c)—R.sup.d, —SO.sub.2—R.sup.e, —P(X.sup.e)(R.sup.f)—R.sup.g, —CH.sub.2—X.sup.f—R.sup.h, or —CH(Me)-X.sup.f—R.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)—CH═CH—, 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.c, 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.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; or 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; 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, 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.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; or 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; 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.3C.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.1C.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.1C.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.3C.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.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 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 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.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 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.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), 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.3alkylsulfonyl, 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.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; 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; wherein “heteroaryl” means an aromatic ring system containing at least one ring heteroatom and consisting either of a single ring or of two fused rings; and wherein the compound of formula (I) is optionally present as an agrochemically acceptable salt thereof.

2. A compound as claimed in claim 1, wherein: R.sup.11 is C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.7cycloalkyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, oxetanyl, tetrahydrothiophene-yl or thietanyl; or R.sup.11 is one of the following sub-formulae A, B, C, D, E, F, GG, H, J, K, L, M, N, O, P, Q, R, S, T, U, V, W, X, Y or Z: ##STR00366## ##STR00367## ##STR00368## ##STR00369## wherein: X.sup.A is nitrogen or CR.sup.13; Y.sup.A is nitrogen or CR.sup.14; Z.sup.A is nitrogen or CR.sup.15; provided that no more than one of X.sup.A, Y.sup.A and Z.sup.A is nitrogen; and R.sup.12 is hydrogen, fluorine, chlorine, bromine, iodine, 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, amino, or phenyl optionally substituted at meta and/or para position(s) by 1 or 2 fluorine substituents; R.sup.13 is hydrogen, fluorine, chlorine, bromine, methyl, ethyl, C.sub.1fluoroalkyl, C.sub.2fluoroalkyl, vinyl, C.sub.2fluoroalkenyl, C.sub.2-C.sub.3alkynyl, fluoroethynyl, cyano, methoxy, ethoxy, C.sub.1fluoroalkoxy, or C.sub.2fluoroalkoxy; R.sup.14 is hydrogen, fluorine, chlorine, bromine, methoxy, C.sub.1fluoroalkoxy, methyl, C.sub.1fluoroalkyl or cyano; R.sup.15 is hydrogen, fluorine, chlorine, bromine, C.sub.1-C.sub.2alkyl, C.sub.1fluoroalkyl, methoxy, C.sub.1fluoroalkoxy, cyano or amino; provided that at least two of R.sup.12, R.sup.13, R.sup.14 and R.sup.15 are hydrogen; and provided that, when R.sup.12 is iodine, amino, or optionally substituted phenyl, then X.sup.A is CR.sup.13, Y.sup.A is CR.sup.14, Z.sup.A is CR.sup.15, and R.sup.13, R.sup.14 and R.sup.15 are independently hydrogen or fluorine, provided that at least two of R.sup.13, R.sup.14 and R.sup.15 are hydrogen; and provided that, when R.sup.13 is bromine, then X.sup.A is CR.sup.13, and R.sup.12, R.sup.14 and R.sup.15 are independently hydrogen or fluorine, provided that at least two of R.sup.12, R.sup.14 and R.sup.15 are hydrogen; and provided that, when R.sup.13 is ethyl, C.sub.2fluoroalkyl, vinyl, C.sub.2fluoroalkenyl, C.sub.2-C.sub.3alkynyl, fluoroethynyl, ethoxy or C.sub.2fluoroalkoxy, then X.sup.A is CR.sup.13, Y.sup.A is CR.sup.14, Z.sup.A is CR.sup.15, and R.sup.12, R.sup.14 and R.sup.15 are independently hydrogen or fluorine, provided that at least two of R.sup.12, R.sup.14 and R.sup.15 are hydrogen; and provided that, when R.sup.14 is bromine or cyano, then X.sup.A is CR.sup.13, Y.sup.A is CR.sup.14, Z.sup.A is CR.sup.15, and of R.sup.12, R.sup.13 and R.sup.15 are independently hydrogen or fluorine, provided that at least two of R.sup.12, R.sup.13 and R.sup.15 are hydrogen; and provided that, when R.sup.15 is amino, then X.sup.A is CR.sup.13, Y.sup.A is nitrogen or CR.sup.14, Z.sup.A is CR.sup.15, and R.sup.13 is hydrogen, methyl or C.sub.1fluoroalkyl, and R.sup.12 and R.sup.14 are hydrogen; and wherein: X.sup.B is nitrogen or CR.sup.13B; Y.sup.B is nitrogen or CR.sup.14B; Z.sup.B is nitrogen or CR.sup.15B; provided that no more than one of X.sup.B, Y.sup.B and Z.sup.B is nitrogen; and R.sup.12B is hydrogen, fluorine, chlorine or bromine; R.sup.13B is hydrogen, fluorine, chlorine, bromine, methyl, C.sub.1fluoroalkyl, cyano, methoxy or C.sub.1fluoroalkoxy; R.sup.14B is hydrogen, fluorine or chlorine; R.sup.15B is hydrogen, fluorine, chlorine or bromine; provided that at least two of R.sup.12B, R.sup.13B, R.sup.14B and R.sup.15B are hydrogen; and provided that, when R.sup.13B is bromine, then X.sup.A is CR.sup.13B, and R.sup.12B, R.sup.14B and R.sup.15B are independently hydrogen or fluorine, provided that at least two of R.sup.12B, R.sup.14B and R.sup.15B are hydrogen; and R.sup.16 is hydrogen, fluorine, chlorine, bromine, methyl or C.sub.1fluoroalkyl; R.sup.17 is hydrogen, fluorine, chlorine, methyl or C.sub.1fluoroalkyl; provided that no more than one of R.sup.16 and R.sup.17 is hydrogen; and provided that when R.sup.16 is bromine then R.sup.17 is hydrogen or fluorine; R.sup.16D is hydrogen or fluorine; R.sup.18 is hydrogen, fluorine or chlorine; R.sup.19 is hydrogen, fluorine, chlorine, methoxy, C.sub.1fluoroalkoxy, methyl or C.sub.1fluoroalkyl; provided that no more than one of R.sup.18 and R.sup.19 is hydrogen; R.sup.15E is hydrogen, fluorine or chlorine; R.sup.12F is hydrogen, fluorine or chlorine; R.sup.11GG is hydrogen, fluorine, methyl or C.sub.1fluoroalkyl; R.sup.12GG is hydrogen, fluorine or chlorine; R.sup.13GG is hydrogen, fluorine, chlorine, bromine, C.sub.1fluoroalkyl, methoxy or C.sub.1fluoroalkoxy; R.sup.14GG is hydrogen or fluorine; R.sup.15GG is hydrogen, fluorine, chlorine, methoxy or C.sub.1fluoroalkoxy; provided that, when R.sup.13GG is bromine, then R.sup.11GG, R.sup.12GG, R.sup.14GG and R.sup.15GG are independently hydrogen or fluorine; provided that, when R.sup.11GG is methyl or C.sub.1fluoroalkyl, then R.sup.12GG, R.sup.13GG, R.sup.14GG and R.sup.15GG are independently hydrogen or fluorine; and provided that at least two of R.sup.12GG, R.sup.13GG, R.sup.14GG and R.sup.15GG are hydrogen; X.sup.K is O or S; and Y.sup.K is C—H or N; X.sup.L is O, S or N-Me; and Y.sup.L is C—H or N; provided that when X.sup.L is N-Me then Y.sup.L is not N; X.sup.m is O, S or N-Me; X.sup.N is O, S or N-Me; X.sup.V is O, S or N-Me; and Y.sup.V is N or CR.sup.42; and X.sup.W is O, S or N-Me; R.sup.20 is hydrogen, methyl, C.sub.1fluoroalkyl, fluorine or chlorine; R.sup.21 is hydrogen, methyl, C.sub.1fluoroalkyl, ethyl, cyclopropyl, fluorine or chlorine; R.sup.22 is hydrogen, methyl, C.sub.1fluoroalkyl, fluorine or chlorine; R.sup.23 is hydrogen, methyl, C.sub.1fluoroalkyl, ethyl or cyclopropyl; R.sup.24 is hydrogen, methyl, C.sub.1fluoroalkyl, ethyl or methoxymethyl; R.sup.25 is hydrogen, methyl, C.sub.1fluoroalkyl, fluorine or chlorine; R.sup.26 is hydrogen or methyl; and R.sup.27 is hydrogen or methyl; and R.sup.28 and R.sup.29 independently are hydrogen or fluorine; R.sup.40 is hydrogen, methyl, C.sub.1fluoroalkyl, fluorine or chlorine; R.sup.41 is hydrogen, methyl, C.sub.1fluoroalkyl, fluorine or chlorine; R.sup.42 is hydrogen, methyl, C.sub.1fluoroalkyl, fluorine or chlorine; R.sup.43 is hydrogen, methyl or C.sub.1fluoroalkyl; R.sup.44 is fluorine, chlorine or bromine; R.sup.12T, R.sup.13T and R.sup.14T are independently hydrogen or fluorine, provided that at least two of R.sup.12T, R.sup.13T and R.sup.14T are hydrogen; and R.sup.12U, R.sup.13U and R.sup.14U are independently hydrogen or fluorine, provided that at least two of R.sup.12U, R.sup.13U and R.sup.14U are hydrogen; and R.sup.13Y is hydrogen, fluorine, chlorine, bromine, C.sub.1fluoroalkyl, methoxy or C.sub.1fluoroalkoxy; R.sup.15Y is hydrogen, fluorine, chlorine, bromine, methoxy or C.sub.1fluoroalkoxy; provided that one or both of R.sup.13Y and R.sup.15Y are independently hydrogen or fluorine; and R.sup.15Z is hydrogen, fluorine or chlorine; and wherein the compound of formula (I) is optionally present as an agrochemically acceptable salt thereof.

3. The compound of claim 1, wherein: R.sup.2 is 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, or (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.11 is C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.7cycloalkyl, tetrahydro-2H-pyranyl or tetrahydrofuranyl; or R.sup.11 is one of the following sub-formulae A, B1, C, D1, E, F, G1, H, J, K, L, M, N, O, P1, Q, R, S, T or U: ##STR00370## ##STR00371## ##STR00372## wherein: X.sup.A is nitrogen or CR.sup.13; Y.sup.A is nitrogen or CR.sup.14; Z.sup.A is nitrogen or CR.sup.15; provided that no more than one of X.sup.A, Y.sup.A and Z.sup.A is nitrogen; and R.sup.12 is hydrogen, fluorine, chlorine, bromine, iodine, 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, amino, or phenyl optionally substituted at meta and/or para position(s) by 1 or 2 fluorine substituents; R.sup.13 is hydrogen, fluorine, chlorine, methyl, C.sub.1fluoroalkyl, or cyano; R.sup.14 is hydrogen, fluorine, chlorine, methoxy, C.sub.1fluoroalkoxy, methyl or C.sub.1fluoroalkyl; R.sup.15 is hydrogen, fluorine, chlorine, bromine, C.sub.1-C.sub.2alkyl, C.sub.1fluoroalkyl, methoxy, C.sub.1fluoroalkoxy, cyano or amino; provided that at least two of R.sup.12, R.sup.13, R.sup.14 and R.sup.15 are hydrogen; and provided that, when R.sup.12 is iodine, amino, or optionally substituted phenyl, then X.sup.A is CR.sup.13, Y.sup.A is CR.sup.14, Z.sup.A is CR.sup.15, and R.sup.13, R.sup.14 and R.sup.15 are independently hydrogen or fluorine, provided that at least two of R.sup.13, R.sup.14 and R.sup.15 are hydrogen; and provided that, when R.sup.15 is amino, then X.sup.A is CR.sup.13, Y.sup.A is nitrogen or CR.sup.14, Z.sup.A is CR.sup.15, and R.sup.13 is hydrogen, methyl or C.sub.1fluoroalkyl, and R.sup.12 and R.sup.14 are hydrogen; and R.sup.16 is hydrogen, fluorine or chlorine; R.sup.17 is hydrogen, fluorine, chlorine, methyl or C.sub.1fluoroalkyl; provided that no more than one of R.sup.16 and R.sup.17 is hydrogen; R.sup.18 is chlorine; R.sup.19 is fluorine, chlorine, methoxy, C.sub.1fluoroalkoxy, methyl or C.sub.1fluoroalkyl; R.sup.15E is hydrogen, fluorine or chlorine; R.sup.12F is hydrogen, fluorine or chlorine; R.sup.12GG is hydrogen, fluorine or chlorine; R.sup.13GG is hydrogen, fluorine, chlorine, C.sub.1fluoroalkyl, methoxy or C.sub.1fluoroalkoxy; R.sup.14GG is hydrogen or fluorine; R.sup.15GG is hydrogen, fluorine, chlorine, methoxy or C.sub.1fluoroalkoxy; provided that at least two of R.sup.12GG, R.sup.13GG, R.sup.14GG and R.sup.15GG are hydrogen; X.sup.K is O or S; and Y.sup.K is C—H or N; X.sup.L is O, S or N-Me; and Y.sup.L is C—H or N; provided that when X.sup.L is N-Me then Y.sup.L is not N; X.sup.m is O, S or N-Me; X.sup.N is O, S or N-Me; R.sup.20 is hydrogen, methyl or C.sub.1fluoroalkyl; R.sup.21 is hydrogen, methyl or C.sub.1fluoroalkyl; R.sup.22 is hydrogen, methyl or C.sub.1fluoroalkyl; R.sup.23 is hydrogen, methyl or C.sub.1fluoroalkyl; R.sup.24 is hydrogen, methyl or C.sub.1fluoroalkyl; R.sup.25 is hydrogen, methyl or C.sub.1fluoroalkyl; R.sup.26 is hydrogen or methyl; and R.sup.27 is hydrogen or methyl; and R.sup.28 and R.sup.29 independently are hydrogen or fluorine; R.sup.12T, R.sup.13T and R.sup.14T are independently hydrogen or fluorine, provided that at least two of R.sup.12T, R.sup.13T and R.sup.14T are hydrogen; and R.sup.12U, R.sup.13U and R.sup.14U are independently hydrogen or fluorine, provided that at least two of R.sup.12U, R.sup.13U and R.sup.14U are hydrogen; 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.c—R.sup.b, —C(X.sup.d)—N(R.sup.c)—R.sup.d, —SO.sub.2—R.sup.e, —P(X.sup.e)(R.sup.f)—R.sup.g, or —CH.sub.2—X.sup.f—R.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)—CH═CH—, 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)-; and wherein 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.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.1C.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.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.1C.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)—; 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; wherein “heteroaryl” means an aromatic ring system containing at least one ring heteroatom and consisting either of a single ring or of two fused rings; and wherein the compound of formula (I) is optionally present as an agrochemically acceptable salt thereof.

4. The compound of claim 2, 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 or —C(X.sup.b)—X.sup.c—R.sup.b, wherein X.sup.a, R.sup.a, X.sup.b, X.sup.c and R.sup.b are as defined in claim 2.

5. The compound of claim 4, wherein: when G is —C(X.sup.a)—R.sup.a or —C(X.sup.b)—X.sup.c—R.sup.b, then X.sup.a and X.sup.b are oxygen, X.sup.c is oxygen or sulfur, R.sup.a is C.sub.1-C.sub.10alkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6alkynyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4alkoxyC.sub.1-C.sub.4alkyl, C.sub.3-C.sub.6cycloalkyl(C.sub.1-C.sub.2)alkyl, or phenyl or phenyl substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.2fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.2fluoroalkoxy, fluorine, chlorine, bromine, cyano or nitro, or a monocyclic 5- or 6-membered heteroaryl or a monocyclic 5- or 6-membered heteroaryl substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.2fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.2fluoroalkoxy, fluorine, chlorine, bromine or cyano; and R.sup.b is C.sub.1-C.sub.10alkyl, C.sub.2-C.sub.5alkenyl-CH.sub.2—, C.sub.2-C.sub.4alkenyl-CH(Me)-, C.sub.2-C.sub.5alkynyl-CH.sub.2—, C.sub.2-C.sub.4alkynyl-CH(Me)-, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4alkoxyC.sub.1-C.sub.4alkyl, C.sub.3-C.sub.6cycloalkyl(C.sub.1-C.sub.2)alkyl, or phenyl or phenyl substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.2fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.2fluoroalkoxy, fluorine, chlorine, bromine, cyano or nitro, or a monocyclic 5- or 6-membered heteroaryl or a monocyclic 5- or 6-membered heteroaryl substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.2fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.2fluoroalkoxy, fluorine, chlorine, bromine or cyano.

6. The compound of claim 5, wherein R.sup.1 is methyl, ethyl, ethynyl, chlorine, bromine or methoxy.

7. The compound of claim 6, wherein R.sup.3 is hydrogen, methyl, ethyl, ethynyl, fluorine, chlorine, bromine, methoxy or fluoromethoxy.

8. The compound of claim 1, wherein: R.sup.2 is methyl, ethynyl, prop-1-ynyl, 2-chloroethynyl, chlorine or bromine; or R.sup.2 is phenyl optionally substituted by 1 or 2 of, independently, halogen, C.sub.1-C.sub.2alkyl, C.sub.1-C.sub.2fluoroalkyl or cyano; or R.sup.2 is monocyclic heteroaryl optionally substituted by 1 or 2 of, independently, halogen, C.sub.1-C.sub.2alkyl, C.sub.1-C.sub.2fluoroalkyl, cyano or nitro; or R.sup.2 is (C.sub.1fluoroalkyl)-methoxy-.

9. The compound as claimed in claim 8, wherein: when R.sup.2 is optionally substituted phenyl, then R.sup.2 is ##STR00373## in which: R.sup.30 is hydrogen, fluorine, chlorine or C.sub.1fluoroalkyl; R.sup.31 is fluorine, chlorine, C.sub.1fluoroalkyl or methyl; R.sup.31A is fluorine or chlorine; R.sup.31B is hydrogen, fluorine or chlorine; and R.sup.31C is hydrogen, fluorine or chlorine; wherein one or both of R.sup.31B and R.sup.31C is or are hydrogen; and when R.sup.2 is optionally substituted monocyclic heteroaryl, then R.sup.2 is ##STR00374## in which: R.sup.32 is hydrogen, fluorine, chlorine or C.sub.1fluoroalkyl; and R.sup.33 is fluorine, chlorine or C.sub.1fluoroalkyl; R.sup.34 is fluorine, chlorine, bromine, methyl, C.sub.1fluoroalkyl or cyano; and R.sup.35 is fluorine, chlorine, bromine, methyl, C.sub.1fluoroalkyl or cyano.

10. The compound as claimed in claim 1, wherein all of R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9 and R.sup.10 are hydrogen.

11. The compound as claimed in claim 1, wherein R.sup.11 is sub-formula A, as defined in claim 2.

12. The compound as claimed in claim 11, wherein: R.sup.11 is sub-formula A; X.sup.A is CR.sup.13; Y.sup.A is CR.sup.14; Z.sup.A is CR.sup.15; R.sup.12 is hydrogen, fluorine, chlorine or bromine; R.sup.13 is hydrogen, fluorine, chlorine, bromine, C.sub.1fluoroalkyl, methoxy or C.sub.1fluoroalkoxy; R.sup.14 is hydrogen, fluorine or chlorine; and R.sup.15 is hydrogen, fluorine, chlorine or bromine; provided that at least two of R.sup.12, R.sup.13, R.sup.14 and R.sup.15 are hydrogen; and provided that, when R.sup.13 is bromine, then R.sup.12, R.sup.14 and R.sup.15 are independently hydrogen or fluorine, provided that at least two of R.sup.12, R.sup.14 and R.sup.15 are hydrogen.

13. The compound as claimed in claim 12, wherein: R.sup.12, R.sup.14 and R.sup.15 are all hydrogen, and R.sup.13 is hydrogen, fluorine, chlorine, bromine or C.sub.1fluoroalkoxy.

14. The compound as claimed in claim 1, wherein the compound of formula (I) is a compound of formula (IC): ##STR00375## 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 in claim 1, and wherein 40% or more by molarity of the compound of formula (IC) has the indicated stereochemistry at the ring-carbon atom bonded to R.sup.6 and —CR.sup.7R.sup.8—CR.sup.9R.sup.10—NHC(O)—R.sup.11.

15. The compound as claimed in claim 14, wherein, more than 50% by molarity of the compound of formula (IC) has the indicated stereochemistry at the ring-carbon atom bonded to R.sup.6 and —CR.sup.7R.sup.8—CR.sup.9R.sup.10—NHC(O)—R.sup.11.

16. The compound as claimed in claim 1, wherein the compound is any of compounds A1 thru A108, present either as a free compound and/or present as an agrochemically acceptable salt thereof: ##STR00376## ##STR00377## ##STR00378## ##STR00379## ##STR00380## ##STR00381## ##STR00382## ##STR00383## ##STR00384## ##STR00385## ##STR00386## ##STR00387## ##STR00388## ##STR00389## ##STR00390## ##STR00391##

17. The compound as claimed in claim 1, wherein the compound is any of compounds A109 to A211 or any of compounds P1 to P30present either as a free compound and/or present as an agrochemically acceptable salt thereof: ##STR00392## ##STR00393## ##STR00394## ##STR00395## ##STR00396## ##STR00397## ##STR00398## ##STR00399## ##STR00400## ##STR00401## ##STR00402## ##STR00403## ##STR00404## ##STR00405## ##STR00406## ##STR00407## ##STR00408## ##STR00409## ##STR00410## ##STR00411## ##STR00412## ##STR00413## ##STR00414## ##STR00415## ##STR00416## ##STR00417## ##STR00418## ##STR00419## ##STR00420## ##STR00421## ##STR00422## ##STR00423## ##STR00424## ##STR00425## ##STR00426## ##STR00427## ##STR00428## ##STR00429## ##STR00430## ##STR00431## ##STR00432## ##STR00433##

18. A compound of formula (Q): ##STR00434## or a salt thereof, when 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 are defined in claim 1.

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

20. The herbicidal composition according to claim 19, which comprises one or more further herbicides and/or a safener.

21. A method of controlling grassy monocotyledonous weeds in crops of useful plants, comprising applying a compound of formula (I), as defined in claim 1, or a herbicidal composition comprising such a compound, to the plants or to locus thereof.

Description

PREPARATION EXAMPLES

(1) Those skilled in the art will appreciate that certain compounds described below are β-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.

(2) Abbreviations Used Herein:

(3) DCM—dichloromethane DMF—N,N-dimethylformamide DMSO—dimethyl sulfoxide EDTA—ethylenediaminetetraacetic acid Hunig's base—N,N-diisopropylethylamine LDA—lithium diisopropylamide LiHMDS—lithium hexamethyldisilazide, also called lithium 1,1,1,3,3,3-hexamethyldisilazan-2-ide, or lithium bis(trimethylsilyl)amide P2tBu—1-tert-butyl-2,2,4,4,4-pentakis(dimethylamino)-2λ.sup.5,4λ.sup.5-catenadi(phosphazene) PTFE—polytetrafluoroethylene SPhos (S-Phos)—2-(dicyclohexylphosphino)-2′,6′-dimethoxybiphenyl TFA—trifluoroacetic acid THF—tetrahydrofuran RT—room temperature (typically ca. 15-30° C. such as ca. 18-25° C.) HPLC—high performance (or high pressure) liquid chromatography MS—mass spectrometry NMR—nuclear magnetic resonance
within .sup.1H NMR spectral data given herein: s=singlet, d=doublet, t=triplet, q=quartet, dd=doublet of doublets, m=multiplet, br.=broad 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)

(4) ##STR00044##

(5) 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).

Example 1

Synthesis of Compound A1

(6) ##STR00045##

Step One: Synthesis of 2-nitroethyl trifluoromethanesulfonate

(7) ##STR00046##

(8) 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 (2×100 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) δ.sub.H 5.00 (t, 2H), 4.75 (t, 2H). .sup.19F NMR (375 MHz, CDCl.sub.3)δ.sub.F-74.1

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

(9) ##STR00047##

(10) 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 (3×100 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 flash chromatography over silica using a 100% hexane to 100% EtOAc gradient to give the desired compound (780 mg, 26%) as a colourless oil. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 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

(11) ##STR00048##

(12) 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. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 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 (2×s, 2×3H), 1.65-1.55 (m, 1H).

Step Four: Synthesis of N-[2-[4-methoxy-2-oxo-3-(2,4,6-trimethylphenyl)cyclopent-3-en-1-yl]ethyl]benzamide

(13) ##STR00049##

(14) To a stirred solution of the crude 5-(2-aminoethyl)-3-methoxy-2-(2,4,6-trimethylphenyl)cyclopent-2-en-1-one (64 mg, 0.234 mmol) in dichloromethane (5 ml), was added Et.sub.3N (65 ul, 0.468 mmol) followed by benzoyl chloride (29 ul, 0.25 mmol). The reaction was stirred at room temperature for 72 hours and then quenched with H.sub.2O (15 ml) and extracted with EtOAc (3×10 ml). The combined organic extracts were washed with brine (10 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 flash chromatography over silica using a 100% hexane to 100% EtOAc gradient to give the desired product (61 mg, 69%) as a colourless oil. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.80 (d, 2H), 7.50-7.35 (m, 4H), 6.85 (2×s, 2H), 3.80 (s, 3H), 3.70-3.60 (m, 2H), 3.10 (dd, 1H), 2.80-2.75 (m, 1H), 2.55 (d, 1H), 2.25 (s, 3H), 2.05 (2×s, 6H), 2.05-1.90 (2H, m).

Step Five: Synthesis of N-[2-[2,4-dioxo-3-(2,4,6-trimethylphenyl)cyclopentyl]ethyl]-benzamide

(15) ##STR00050##

(16) A solution of N-[2-[4-methoxy-2-oxo-3-(2,4,6-trimethylphenyl)cyclopent-3-en-1-yl]ethyl]benzamide (48 mg, 0.127 mmol) in acetone (1 ml) and 2M HCl (1 ml) was heated at 80° for 50 minutes under microwave irradiation. The reaction was cooled to room temperature, diluted with H.sub.2O and extracted with EtOAc (3×10 ml). The combined organic extracts were washed with brine (10 ml), dried over MgSO.sub.4, filtered and evaporated to dryness under reduced pressure to give a pale brown oil. The crude product was purified by flash chromatography over silica using a 100% hexane to 100% EtOAc gradient to give the desired product (25 mg, 54%) as a colourless oil. .sup.1H NMR (400 MHz, d6-acetone) δ 8.30 (br, 1H), 7.97-7.93 (m, 2H), 7.60-7.55 (m, 1H), 7.50-7.45 (m, 2H), 6.85 (s, 2H), 3.80-3.70 (br, 1H), 3.60-3.50 (m, 1H), 3.00-2.70 (m, 2H), 2.25 (s, 3H), 2.15-2.05 (m, 1H), 2.05 (2×s, 2×3H), 1.95-1.90 (m, 1H)

Example 2

Synthesis of Compound A44

(17) ##STR00051##

Step One: Synthesis of 1-nitroethylene

(18) ##STR00052##

(19) 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 dissolved in 100 mL of anhydrous tetrahydrofuran, dried over anhydrous CaCl.sub.2 and stored as a solution in tetrahydrofuran (33.34 g, 69%). .sup.1H NMR (400 MHz, CDCl.sub.3) δ 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

(20) ##STR00053##

(21) 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) was then added dropwise over 1 hr using a dropping funnel. Once the addition was complete the mixture was stirred 30 mins before being allowed to warm to room temperature. After stirring 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 (3×20 mL). The combined organic extracts were dried, filtered and evaporated to dryness. The crude product was purified by flash chromatography over silica 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) δ 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

(22) ##STR00054##

(23) 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 two hours at room temperature and then filtered through a pad of celite and the filtrate evaporated to dryness under reduced pressure. The residue was then dissolved in dichloromethane (20 mL) and washed with saturated sodium bicarbonate solution (2×10 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).

Step Four: Synthesis of 3-chloro-N-[2-[2,4-dioxo-3-(2,4,6-trimethylphenyl)cyclopentyl]ethyl]pyridine-2-carboxamide

(24) ##STR00055##

(25) To a stirred solution of the 5-(2-aminoethyl)-3-methoxy-2-(2,4,6-trimethylphenyl)cyclopent-2-en-1-one (0.250 g, 0.91 mmol) in N,N-dimethylformamide (9 mL) was added Hunig's base (N,N-diisopropylethylamine) (0.40 mL, 2.29 mmol) and 3-chloropicolinic acid (0.16 g, 1.01 mmol). The reaction was then cooled to 0° C. and benzotriazol-1-yloxy(tripyrrolidin-1-yl)phosphonium hexafluorophosphate (0.97 g, 1.83 mmol) was added. Once the addition was complete the reaction was allowed to warm to room temperature and stirred two hours. The reaction was then evaporated to dryness under reduced pressure and the crude product carried forward to the next step without further purification.

(26) To a solution of the crude enol ether in EtOH (4 mL) was added 2M hydrochloric acid (4 mL) and the mixture was then heated to 60° C. for 4 hours. The reaction was then allowed to cool to room temperature and then evaporated to dryness under reduced pressure. The crude product was then purified on a FractionLynx mass-directed purification system to give the desired product (0.072 g, 18%) as an off-white solid. .sup.1H NMR (400 MHz, d4-methanol) δ, 8.50-8.54 (m, 1H), 7.94-7.98 (m, 1H), 7.47-7.52 (m, 1H), 6.84-6.88 (s, 2H) 3.49-3.64 (m, 2H), 2.91-2.99 (m, 1H), 2.81-2.90 (m, 1H), 2.47-2.55 (m, 1H), 2.16-2.27 (m, 4H), 2.03-2.07 (s, 6H), 1.67-1.78 (1H, m).

Example 3

Synthesis of Compound A84

(27) ##STR00056##

Step One: Synthesis of 2-(4-bromo-2-ethyl-6-methyl-phenyl)-3-methoxy-5-(2-nitroethyl)cyclopent-2-en-1-one

(28) ##STR00057##

(29) To a solution of 2-(4-bromo-2-ethyl-6-methyl-phenyl)-3-methoxy-cyclopent-2-en-1-one (8.0 g, 25.87 mmol) in tetrahydrofuran (130 mL), under a nitrogen atmosphere at −50° C. to −60° C. was added dropwise lithium diisopropylamide solution (1.8M in tetrahydrofuran/ether/benzene) (25.87 mmol, 14.4 mL) keeping the temperature constant. The mixture was then stirred for 30 mins at −50° C. to −60° C. A solution of 1-nitroethylene (0.98 equiv., 25.36 mmol, 14.94 mL, 1.852 g) in tetrahydrofuran was then added very slowly, once again keeping the temperature constant. The reaction mixture was stirred for 30 mins before being allowed to warm to room temperature. The mixture was stirred at room temperature for 1 hr before being quenched by the addition of saturated ammonium chloride (100 ml). The mixture was then extracted with dichloromethane (3×100 ml). The combined organic extracts were dried over MgSO.sub.4, filtered and evaporated to dryness under reduced pressure. The crude product was purified by flash chromatography over silica using an EtOAc/hexane gradient to give the desired product (5.64 g, 57%) as a brown oil. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.22 (s, 2H), 4.67 (t, 2H), 3.75 (s, 3H), 3.10-3.03 (m, 1H), 2.75-2.65 (m, 1H), 2.50-2.15 (m, 5H), 2.09 (s, 3H), 1.15-1.08 (m, 3H).

Step Two: Synthesis of N-[2-[3-(4-bromo-2-ethyl-6-methyl-phenyl)-4-methoxy-2-oxo-cyclopent-3-en-1-yl]ethyl]pyridine-2-carboxamide

(30) ##STR00058##

(31) To a suspension of 2-(4-bromo-2-ethyl-6-methyl-phenyl)-3-methoxy-5-(2-nitroethyl)cyclopent-2-en-1-one (5.269 g, 13.79 mmol) in EtOH (70 mL) under a nitrogen atmosphere was added conc. HBr (10.54 mL, 194 mmol). Zn dust (1.80 g, 27.57 mmol) was added and the substrate immediately went into solution and an exotherm was observed. The reaction was brought back to room temperature using ice bath cooling and stirred at room temperature for 4 hrs. The reaction was then cooled to 0° C., and a further portion of Zn dust (1.80 g, 27.57 mmol) was added portion wise. The reaction was allowed to warm to room temperature, and stirred for a further 2 hours. The reaction was poured onto water (100 ml) and the pH was carefully adjusted to ˜7 by the addition of saturated aqueous sodium hydrogen carbonate solution. The resulting white powder was filtered off, washed with saturated aqueous sodium hydrogen carbonate, hexane and a little ether and dried under reduced pressure to give the crude amine as a white solid (9.8 g).

(32) To the crude amine (8.84 g) in dichloromethane (90 ml) at 10° C. was added Hunig's base (5.14 ml, 30.1 mmol) followed by portion wise addition of pyridine-2-carbonyl chloride hydrochloride (5.36 g, 30.1 mmol), keeping the temperature under 10° C. The reaction was then allowed to warm to room temperature and stirred for a further 3 hours. The reaction was quenched by the addition of saturated aqueous ammonium chloride (200 ml) and extracted with dichloromethane (2×200 ml). The combined organics were passed through a PTFE frit and purified by flash chromatography over silica to give the desired compound (1.27 g, 11%) as a sticky, off-white solid. .sup.1H NMR (400 MHz, CDCl.sub.3) δ (delta) 1.08 (td, 3H), 1.73-1.84 (m, 1H), 2.06 (s, 1.5H), 2.08 (s, 1.5H), 2.19-2.31 (m, 1H), 2.32-2.47 (m, 2H), 2.63 (dd, 1H), 2.70-2.79 (m, 1H), 3.10 (ddd, 1H), 3.55-3.66 (m, 1H), 3.69-3.76 (m, 1H), 3.78 (s, 3H), 7.18-7.25 (m, 2H), 7.44 (ddd, 1H), 7.86 (td, 1H), 8.19 (d, 1H), 8.27 (br. s., 1H), 8.56 (d, 1H).

Step Three: Synthesis of N-[2-[3-(2-ethyl-6-methyl-4-prop-1-ynyl-phenyl)-4-methoxy-2-oxo-cyclopent-3-en-1-yl]ethyl]pyridine-2-carboxamide

(33) ##STR00059##

(34) To a flask charged with N-[2-[3-(4-bromo-2-ethyl-6-methyl-phenyl)-4-methoxy-2-oxo-cyclopent-3-en-1-yl]ethyl]pyridine-2-carboxamide (320 mg, 0.6996 mmol), Dichloro[1,1-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (78.4 mg, 0.105 mmol), Copper(I) iodide (27 mg, 0.14 mmol) and caesium fluoride (0.2147 g, 1.4 mmol) under a nitrogen atmosphere is added dry, degassed N,N-dimethylformamide (3.2 mL), followed by tributyl(1-propynyl)tin (0.2666 g, 0.77 mmol) and the reaction heated to 100° C. for 3 hours. The reaction was allowed to cool to room temperature and diluted with EtOAc (50 ml) and washed with saturated aqueous ammonium chloride (50 ml). The organic layer was separated, washed with saturated brine (2×50 ml), and the organic layer passed through a PTFE frit, dry loaded onto silica and purified by flash chromatography over silica using an EtOAc/hexane gradient to give the desired compound (0.184 g, 63%) as a mixture of atropisomers. .sup.1H NMR (400 MHz, CDCl.sub.3) δ (delta) 8.56 (d, 1H), 8.27 (br, 1H), 8.19 (d, 1H), 7.90-7.80 (m, 1H), 7.47-7.40 (m, 1H), 7.15-7.07 (m, 2H), 3.78-3.69 (m, 4H) 3.10-3.06 (m, 1H), 3.66-3.55 (m, 1H), 2.77-2.69 (m, 1H), 2.61 (dd, 1H) 2.4-2.32 (m, 2H), 2.31-2.21 (m, 1H), 2.07 (s, 1.5H), 2.05 (s, 1.5H), 2.03 (s, 3H), 1.85-1.73 (m, 1H), 1.10-1.06 (m, 3H).

Step Four: Synthesis of N-[2-[3-(2-ethyl-6-methyl-4-prop-1-ynyl-phenyl)-2,4-dioxo-cyclopentyl]ethyl]pyridine-2-carboxamide

(35) ##STR00060##

(36) To a stirred solution of N-[2-[3-(2-ethyl-6-methyl-4-prop-1-ynyl-phenyl)-4-methoxy-2-oxo-cyclopent-3-en-1-yl]ethyl]pyridine-2-carboxamide (184 mg, 0.4418 mmol) in acetone (1 mL) was added 2M HCl (1 ml) and the reaction was heated to 50° C. for 5 hours. The reaction was concentrated under reduced pressure to remove excess acetone, diluted with EtOAc (25 ml) and extracted with 1M K.sub.2OC.sub.3 solution (25 ml). The organic layer was set aside and the aqueous layer was then acidified to pH6 with concentrated HCl (a precipitate was observed) and extracted with EtOAc (25 ml). This organic layer gave a poor recovery, so the initial EtOAc layer was washed with saturated aqueous ammonium chloride (25 ml), and combined with the other organic washing. This was then dry loaded onto silica and purified by flash chromatography over silica using a 2-10% MeOH in dichloromethane gradient to give the desired compound (105 mg, 59%) as a brown gum as a mixture of atropisomers. .sup.1H NMR (400 MHz, CDCl.sub.3) δ (delta) 1.12 (dt, 3H), 1.78-1.94 (m, 2H), 2.04 (s, 3H), 2.11 (s, 1.5H), 2.15 (s, 1.5H), 2.18 (d, 1H), 2.44 (dt, 2H), 2.81-3.04 (m, 2H), 3.35-3.53 (m, 1H), 4.04-4.25 (m, 1H), 7.05-7.19 (m, 2H), 7.46-7.60 (m, 1H), 7.91 (t, 1H), 8.22 (d, 1H), 8.61 (d, 1H), 8.69 (br. s., 1H), 12.25 (br. s., 1H).

Example 4

Synthesis of Compound A85

(37) ##STR00061##

Step One: Synthesis of N-[2-[3-[2-ethyl-6-methyl-4-(2-trimethylsilylethynyl)phenyl]-4-methoxy-2-oxo-cyclopent-3-en-1-yl]ethyl]pyridine-2-carboxamide

(38) ##STR00062##

(39) To a flask charged with N-[2-[3-(4-bromo-2-ethyl-6-methyl-phenyl)-4-methoxy-2-oxo-cyclopent-3-en-1-yl]ethyl]pyridine-2-carboxamide (314 mg, 0.69 mmol) and palladium-tetrakis(triphenylphosphine) (0.034 mmol, 0.04 g) under nitrogen was added degassed, dry toluene (10 ml), followed by trimethyl(2-tributylstannylethynyl)silane (0.83 mmol, 0.32 g), and the reaction heated to 100° C. for 17 hours. Reaction was filtered through a frit, dry loaded onto silica and purified by flash chromatography over silica using a 30-100% EtOAc in hexane gradient to give the desired compound (283 mg, 97%) as a pale yellow gum as a mixture of atropisomers. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.56 (d, 1H), 8.27 (br s, 1H), 8.19 (d, 1H), 7.86 (td, 1H), 7.41-7.46 (m, 1H), 7.15-7.22 (m, 2H), 3.73-3.80 (m, 1H), 3.72 (s, 3H), 3.56-3.65 (m, 1H), 3.07 (ddd,1H), 2.69-2.78 (m, 1H), 2.61 (dd, 1H), 2.33-2.45 (m, 2H), 2.25 (dd, 1H), 2.07 (s, 1.5H), 2.05 (s, 1.5H), 1.75-1.84 (m, 1H), 1.08 (td, 3H), 0.21-0.26 (m, 9H).

Step Two: Synthesis of N-[2-[3-(2-ethyl-4-ethynyl-6-methyl-phenyl)-4-methoxy-2-oxo-cyclopent-3-en-1-yl]ethyl]pyridine-2-carboxamide

(40) ##STR00063##

(41) To a solution of N-[2-[3-[2-ethyl-6-methyl-4-(2-trimethylsilylethynyl)phenyl]-4-methoxy-2-oxo-cyclopent-3-en-1-yl]ethyl]pyridine-2-carboxamide (283 mg, 0.5962 mmol) in tetrahydrofuran (10 mL) at 0° C. was added dropwise, tetrabutyl ammonium fluoride (1.0 mol/L) in tetrahydrofuran (3 equiv., 1.8 mL, 1.789 mmol, 1.0 mol/L) over a period of 2 minutes. The reaction was then allowed to warm to ambient and stirred for a further 90 minutes. The reaction was quenched by the addition saturated aqueous ammonium chloride (25 ml), and extracted with ethyl acetate (25 ml), the organic layer is then filtered through a PTFE frit, dry loaded onto silica and purified by flash chromatography over silica using a 50-100% EtOAc in hexane gradient to give the desired product as a mixture of atropisomers (207 mg, 86%) as a gum without need for further purification. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.56 (d, 1H), 8.27 (br, 1H), 8.19 (d, 1H) 7.86 (td, 1H) 7.17-7.25 (m, 2H), 7.41-7.47 (m, 1H), 3.76 (s, 3H) 3.69-3.74 (m, 1H), 3.55-3.65 (m, 1H), 3.10 (ddd, 1H), 3.02 (s, 1H), 2.74 (ddd, 1H), 2.63 (dd, 1H), 2.34-2.45 (m, 2H), 2.20-2.32 (m, 1H) 2.09 (s, 1.5H), 2.07 (s, 1.5H), 1.73-1.85, (m, 1H), 1.09 (td, 3H).

Step Three: Synthesis of N-[2-[3-(2-ethyl-4-ethynyl-6-methyl-phenyl)-2,4-dioxo-cyclopentyl]ethyl]pyridine-2-carboxamide

(42) ##STR00064##

(43) To a solution of N-[2-[3-(2-ethyl-4-ethynyl-6-methyl-phenyl)-4-methoxy-2-oxo-cyclopent-3-en-1-yl]ethyl]pyridine-2-carboxamide (207 mg, 0.5143 mmol) in acetone (1 mL) was added 2 N HCl (1 mL) and the reaction heated to 50° C. for 5 hours. The reaction was concentrated in vacuo to remove excess acetone, diluted with 2 N HCl (25 ml), and extracted with EtOAc (25 ml) (the organic layer was reserved). The aqueous layer was then adjusted to pH6 with 2N K.sub.2CO.sub.3 and extracted with EtOAc (25 ml). The initial EtOAc layer was washed with saturated aqueous ammonium chloride (25 ml), and combined with the other organic washing. This was then dry loaded onto silica and purified by flash chromatography over silica using a 2-10% MeOH in dichloromethane gradient to give the desired product (167 mg, 84%) as a sticky solid. .sup.1H NMR (400 MHz, CDCl.sub.3) δ (delta) 1.05-1.18 (m, 3H), 1.87 (t, 1H), 2.10-2.23 (m, 4H), 2.40-2.56 (m, 2H), 2.83-3.00 (m, 2H), 3.01 (s, 1H), 3.43 (d, 1H), 4.08-4.21 (m, 1H), 7.20-7.26 (m, 2H), 7.42-7.50 (m, 1H), 7.92 (t, 1H), 8.22 (d, 1H), 8.61 (d, 1H), 8.71 (br. s., 1H).

Example 5

Synthesis of Compound A86

(44) ##STR00065##

Step One: Synthesis of N-[2-[3-[2-ethyl-4-(4-fluorophenyl)-6-methyl-phenyl]-4-methoxy-2-oxo-cyclopent-3-en-1-yl]ethyl]pyridine-2-carboxamide

(45) ##STR00066##

(46) To a solution of N-[2-[3-(4-bromo-2-ethyl-6-methyl-phenyl)-4-methoxy-2-oxo-cyclopent-3-en-1-yl]ethyl]pyridine-2-carboxamide (200 mg, 0.4373 mmol) in 1,4-dioxane (2 mL) was added cesium fluoride (3 equiv., 1.312 mmol, 0.1993 g), (4-fluorophenyl)boronic acid (1.5 equiv., 0.6559 mmol, 0.09177 g) and bis(diphenylphosphino)ferrocenedichloropalladium (II) (0.2 equiv., 0.08745 mmol, 0.06399 g). The reaction was then heated under microwave irradiation at 120° C. for 45 mins. The reaction was diluted with ethyl acetate (20 ml) and filtered through celite. The organic filtrate was then reduced in vacuo before purification by flash chromatography over silica using an EtOAc/hexane gradient to give the desired product (183 mg, 89%) as a brown gum.

Step Two: Synthesis of N-[2-[3-[2-ethyl-4-(4-fluorophenyl)-6-methyl-phenyl]-2,4-dioxo-cyclopentyl]ethyl]pyridine-2-carboxamide

(47) ##STR00067##

(48) To a solution of N-[2-[3-[2-ethyl-4-(4-fluorophenyl)-6-methyl-phenyl]-4-methoxy-2-oxo-cyclopent-3-en-1-yl]ethyl]pyridine-2-carboxamide (187 mg, 0.3957 mmol) in acetone (1 mL) was added 2 N HCl (1 mL) and the reaction heated to 50° C. for 5 hours. The reaction was concentrated in vacuo to remove excess acetone, the aqueous layer adjusted to a pH of about 7 with 2N K.sub.2CO.sub.3 followed by saturated aqueous ammonium chloride (25 ml) and extracted with EtOAc (25 ml). The organic layer is dry loaded onto silica and purified by flash chromatography over silica using a 50-100% EtOAc in hexane gradient to give the desired product (169 mg, 93% yield) as a mixture of atropisomers. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 12.35 (br, 1H), 8.71 (br, 1H), 8.62 (d, 1H), 8.23 (d, 1H), 7.96-7.88 (m, 1H), 7.57-7.49 (m, 3H), 7.26 (s, 2H), 7.10 (t, 2H), 4.18 (d, 1H), 3.44 (d, 1H), 3.04-2.96 (m, 1H), 2.96-2.88 (m, 1H), 2.58-2.54 (m, 2H), 2.26 (s, 1.5H), 2.22 (s, 1.5H), 2.26-2.17 (m, 2H), 1.89 (t, 1H), 1.20-1.16 (m, 3H).

Example 6

Synthesis of Compound A87

(49) ##STR00068##

Step One: Synthesis of N-[2-[3-[4-(4-chloropyrazol-1-yl)-2-ethyl-6-methyl-phenyl]-2,4-dioxo-cyclopentyl]ethyl]pyridine-2-carboxamide

(50) ##STR00069##

(51) To a 3-neck flask charged with N-[2-[3-(4-bromo-2-ethyl-6-methyl-phenyl)-4-methoxy-2-oxo-cyclopent-3-en-1-yl]ethyl]pyridine-2-carboxamide (340 mg, 0.7433 mmol) was added 4-chloropyrazole (2 equiv., 1.487 mmol, 0.1524 g), copper iodide (2 equiv., 1.487 mmol, 0.2831 g), dimethyl glycine (4 equiv., 2.973 mmol, 0.3066 g) and potassium carbonate (4 equiv., 2.973 mmol, 0.4151 g) and the vessel was purged with nitrogen. Dimethyl sulfoxide (anhydrous) (6.8 mL) was then added, and the reaction heated to 140° C. for 90 mins. The reaction was filtered through a PTFE frit, diluted with EtOAc (50 ml) and extracted with 2N K.sub.2CO.sub.3 (25 ml). The organic layer was neutralised with saturated aqueous ammonium chloride (50 ml) and extracted with EtOAc (50 ml) and washed with brine (3×50 ml). The organic layer was then filtered through a PTFE frit, dry loaded onto silica and purified by flash chromatography over silica using an EtOAc/hexane gradient to give the desired product (63 mg, 18%) as a brown gum. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.71 (br s, 1H), 8.61 (d, 1H), 8.22 (d, 1H), 7.84-8.01, (m, 2H), 7.62 (s, 1H), 7.49-7.57 (m, 1H), 7.32-7.40 (m, 2H), 4.11-4.25 (m, 1H), 3.46 (br s, 1H), 2.83-3.05 (m, 2H), 2.54 (dt, 2H), 2.23 (d, 5H), 1.88 (br s, 1H), 1.11-1.23 (m, 3H).

Example 7

Chiral HPLC separation of enantiomers of compound A34 (to compounds A98 and A99)

(52) ##STR00070##

(53) Compound A34 (racemic), was separated into the enantiomer compounds A98 and A99 using a chiral HPLC column, by the following method and under the following conditions.

(54) The chiral HPLC column used was a (s,s) WhelkO1—5 micron—21 mm×250 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.

(55) The solvent system used as an eluent for the column was a 30:70 (by volume) mixture of Solvent A and Solvent B, in which:

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

(57) Other conditions were as follows: Flow rate through column: 21 ml/minute. Run time: 20 minutes. Loading (compound loaded onto column): 50 mg/ml of compound in ethanol. Volume of sample (compound) injected per run=1800 microliters. Number of injections of compound=5. Amount of racemic compound A34 used: 350 mg

(58) Chiral HPLC on a total of 350 mg of compound A34 under the above conditions gave 131 mg of compound A98 (100% enantiomeric excess (e.e.), retention time 12.04 minutes under the above conditions) and 135 mg of compound A99 (99.1% enantiomeric excess (e.e.), retention time 14.26 minutes under the above conditions).

(59) Abbreviation: HPLC=high performance (or high pressure) liquid chromatography.

(60) Alternative Embodiment: Chiral HPLC Separation of Compound A87 into Enantiomer Compounds A100 and A101

(61) Using generally similar conditions (e.g. see above, and see below), compound A87 was separated into enantiomer compounds A100 and A101.

(62) General Note on Chiral HPLC Separation of Enantiomers:

(63) The above procedure using chiral HPLC can be used to separate the enantiomers of other compounds of formula (I) of the present the invention. Chiral columns which might be useful to achieve this are as follows:

(64) (s,s) WhelkO1—5 micron—21 mm×250 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-tetrahydrophenanthren];

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

(66) Kromasil® CelluCoat™ [whose chiral stationary phase is tris-(3,5-dimethylphenyl)carbamoyl cellulose]; Chiralpak® IA [whose chiral stationary phase is a (3,5-dimethylphenyl)carbamate derivative of amylose]; Chiralpak® IB [whose chiral stationary phase is tris-(3,5-dimethylphenyl)carbamate derivative of cellulose]; Chiralpak® IC [whose chiral stationary phase is cellulose tris(3,5-dichlorophenyl)carbamate]; Lux® Amylose-2 [whose chiral stationary phase is amylose tris(5-chloro-2-methylphenylcarbamate)]; or Lux® Cellulose-2 [whose chiral stationary phase is Cellulose tris(3-chloro-4-methylphenylcarbamate)].

Intermediate 2

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)

(67) ##STR00071##

(68) 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 continued for 2 hours. A solution of saturated aqueous ammonium chloride (30 ml) is added, and the mixture is extracted with dichloromethane (3×25 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 column 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)

(69) ##STR00072##

(70) 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 (2×50 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 column 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)

(71) ##STR00073##

(72) 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 (3×250 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 column 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

(73) ##STR00074##
also present as

(74) ##STR00075##

(75) 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 ml×2) and the solution is concentrated in vacuo. Distilled water is added and the crude product is extracted with ethyl acetate (500 ml×3). 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

(76) ##STR00076##

(77) 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 (3×500 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 flash column chromatography to afford 2-(4-bromo-2,6-dimethyl-phenyl)-3-methoxy-cyclopent-2-en-1-one.

Example 8

Synthesis of Compound A126

(78) ##STR00077##

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

(79) ##STR00078##

(80) To a solution of 2-(4-bromo-2,6-dimethyl-phenyl)-3-methoxy-cyclopent-2-en-1-one (11.0 g, 37.3 mmol) (which can e.g. be prepared by the method described in Intermediate 2 herein) in dry THF (90 mL) at −78° C. was added potassium hexamethyldisilazide (45 mL, 41 mmol, 0.91 mol/L in THF) over 2 min. The mixture was warmed to 0° C. and stirred for 30 min, then cooled to −78° C. 2-Bromoacetonitrile (2.90 mL, 41.6 mmol) was added dropwise and the mixture was then warmed to 0° C. and stirred for 1 h. 0.5M saturated aqueous NH.sub.4Cl (200 mL) was added and the THF was removed under reduced pressure. The residue was extracted with ethyl acetate (2×100 mL) and the combined organic layers were washed with brine (50 mL), then dried over MgSO.sub.4 and concentrated under reduced pressure. The residue was purified by flash chromatography over silica using an EtOAc/hexane gradient to give the desired product (6.42 g, 52%) as a pale brown solid. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.24 (s, 1H), 7.23 (s, 1H), 3.57 (s, 3H), 3.20-3.30 (m, 1H), 2.73-2.93 (m, 3H), 2.50 (dd, 1H), 2.21 (s, 3H), 2.12 (s, 3H).

Step Two: Synthesis of 2-[3-[2,6-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2-methoxy-4-oxo-cyclopent-2-en-1-yl]acetonitrile

(81) ##STR00079##

(82) To a mixture of 2-[3-(4-bromo-2,6-dimethyl-phenyl)-2-methoxy-4-oxo-cyclopent-2-en-1-yl]acetonitrile (10.80 g, 32.3 mmol), 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (11.8 g, 45.8 mmol), potassium acetate (4.36 g, 44.4 mmol) and SPhos (1.01 g, 2.39 mmol) in 1,4-dioxane (150 mL) was added tris(dibenzylideneacetone)dipalladium(0) (1.10 g, 1.20 mmol). The mixture was degassed by stirring with nitrogen bubbling for 10 min, then heated at 85° C. for 4 h total, then cooled to room temperature. The solvent was removed under reduced pressure, and the residue was dissolved in ethyl acetate (80 mL) and filtered through celite, rinsing with water (50 mL). The Phases were separated and the aqueous layer was extracted with ethyl acetate (50 mL). The combined organic layers were washed with brine (50 mL), then dried over MgSO.sub.4 and concentrated under reduced pressure. The residue was purified by flash chromatography over silica using an EtOAc/hexane gradient and the material obtained was purified further by trituration with EtOAc/hexane to give the desired product (8.78 g, 71%) as a beige solid. .sup.1H NMR (400 MHz, CDCl.sub.3) δ (delta) 7.52 (s, 1H), 7.50 (s, 1H), 3.53 (s, 3H), 3.21-3.30 (m, 1H), 2.89 (dd, 1H), 2.74-2.85 (m, 2H), 2.50 (dd, 1H), 2.23 (s, 3H), 2.15 (s, 3H), 1.34 (s, 12H).

Step Three: Synthesis of N-[2-[3-[2,6-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl]pyridine-2-carboxamide

(83) ##STR00080##

(84) An autoclave was charged with Raney Nickel (2800) (7.3 g), (2,3,4,5,6-pentafluorophenyl)pyridine-2-carboxylate (5.70 g, 19.7 mmol), 2-[3-[2,6-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2-methoxy-4-oxo-cyclopent-2-en-1-yl]acetonitrile (5.00 g, 13.1 mmol) in 1,2-dimethoxyethane (125 mL). The mixture was pressurised to 3.5 Bar with hydrogen and stirred vigorously at room temperature, with further Raney Nickel (2800) (2.0 g) being added at 2 h intervals before continuing the reaction under the same conditions. After a total of 6 h, the mixture was filtered through Celite™, rinsing with dimethoxyethane then with methanol. The filtrate was concentrated under reduced pressure and the residue was purified by flash chromatography over silica using an EtOAc/hexane gradient to give the desired product (4.59 g, 71%) as a pale yellow foam. .sup.1H NMR (400 MHz, CDCl.sub.3) δ (delta) ppm 8.55 (d, 1H), 8.17-8.24 (m, 2H), 7.86 (td, 1H), 7.49 (s, 2H), 7.44 (ddd, 1H), 3.58-3.69 (m, 2H), 3.49 (s, 3H), 3.02 (dddd, 1H), 2.84 (dd, 1H), 2.38 (dd, 1H), 2.22-2.33 (m, 1H), 2.15 (d, 6H), 1.79 (dq, 1H), 1.33 (s, 12H).

Step Four: Synthesis of N-[2-[3-[2,6-dimethyl-4-(2,2,2-trifluoroethoxy)phenyl]-2,4-dioxo-cyclopentyl]ethyl]pyridine-2-carboxamide (compound A126)

(85) ##STR00081##

(86) N-[2-[3-[2,6-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl]pyridine-2-carboxamide (100 mg, 0.204 mmol) was combined with copper (II) acetate (78 mg, 0.43 mmol) and triethylamine (0.11 mL, 0.79 mmol) in 2,2,2-trifluoroethanol (1.5 mL). The resulting slurry was sealed in a microwave vial and heated at 70° C. for 40 min then concentrated under reduced pressure. The residue was partitioned between 0.5M aqueous tetrasodium EDTA (10 mL, 5 mmol) and ethyl acetate (10 mL). The phases were separated and the organic layer was washed with 0.5M aqueous tetrasodium EDTA (10 mL, 5 mmol), water (10 mL) and brine (5 mL). The organic layer was then dried over MgSO.sub.4 and concentrated under reduced pressure. The residue was purified by flash chromatography over silica using an EtOAc/hexane gradient to give a mixture of the desired product and protodeborylated starting material, which was taken into the next step without further purification. The crude product (60 mg) was dissolved in a mixture of acetone (2 mL) and 2M aqueous HCl (2 mL) and heated under reflux for 2 h, then cooled to room temperature and concentrated under reduced pressure to remove acetone. The pH of the aqueous mixture was adjusted to 4-5 by addition of saturated aqueous NaHCO.sub.3, then extracted with EtOAc (3×5 mL). The combined organic layers were dried over MgSO.sub.4 and concentrated under reduced pressure, and the residue was purified by mass-directed Fraction preparative HPLC to give the desired product (21 mg, 23% over two steps) as a colourless gum. .sup.1H NMR (400 MHz, CDCl.sub.3) δ (delta) 8.64 (br. s., 1H), 8.59 (d, 1H), 8.16 (d, 1H), 7.89 (td, 1H), 7.50 (dd, 1H), 6.64 (s, 2H), 4.29 (q, 2H), 3.81-4.16 (m, 1H), 3.35-3.57 (m, 1H), 2.82-3.00 (m, 2H), 2.26 (d, 1H), 2.02-2.19 (m, 7H), 1.83-2.02 (m, 1H).

(87) General Note on Mass Directed Preparative HPLC

(88) Compounds purified by mass directed prep HPLC using ES+ on a Waters Fraction Lynx system comprising a 2767 injector/collector with a 2545 gradient pump, two 515 isocratic pumps, SFO, 2998 photodiode array, 2424 ELSD and 3100 mass spectrometer. A Waters XBridge dC18 5 micron 19×10 mm guard column was used with an ACT ACE C18-AR, 5 micron 30×100 mm preparative column.

(89) The preparative HPLC was conducted using a 11.4 minute run time using at column dilution, according to the following gradient table:

(90) TABLE-US-00010 For P2_10min_Foc2_0 Time Solvent A Solvent B Flow (mins) (%) (%) (ml/mn) 0.00 85 15 33 1.50 85 15 33 1.51 50 50 33 7.0 30 70 33 7.3 0 100 33 9.2 0 100 33 9.8 95 5 33 11.35 95 5 33 11.40 95 5 33 515 pump 2 ml/min CH.sub.3CN with 0.05% TFA 515 pump 2 ml/min 90% MeOH/10% H.sub.2O (make up pump) Solvent A: H.sub.2O with 0.05% TFA Solvent B: CH.sub.3CN with 0.05% TFA

Example 9

Synthesis of Compound A142

(91) ##STR00082##

Step One: Synthesis of N-[2-[3-[4-(4-cyanopyrazol-1-yl)-2,6-dimethyl-phenyl]-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl]pyridine-2-carboxamide

(92) ##STR00083##

(93) N-[2-[3-[2,6-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl]pyridine-2-carboxamide (200 mg, 0.408 mmol) was combined with copper (II) acetate (230 mg, 1.27 mmol), potassium carbonate (90 mg, 0.64 mmol) and 1H-pyrazole-4-carbonitrile hydrochloride (78 mg, 0.60 mmol) in pyridine (3 mL). The mixture was heated at 80° C. under nitrogen for 5 hours in total, then cooled to room temperature and concentrated under reduced pressure. The residue was partitioned between EtOAc (10 mL) and 0.5M aqueous tetrasodium EDTA (10 mL, 5 mmol) and the mixture was filtered through Celite. The phases were separated and the organic layer was washed with 0.5M tetrasodium EDTA (5 mL, 2.5 mmol), then dried over MgSO.sub.4 and concentrated under reduced pressure. The residue was partially purified by flash chromatography over silica using an EtOAc/hexane gradient. The impure material obtained was redissolved in 1:1 EtOAc/ether and washed with 2M aqueous NaOH (3×10 mL) then brine (10 mL). The organic layers were dried over MgSO.sub.4 and concentrated under reduced pressure to give the desired product (28 mg, 14%) as a colourless gum. .sup.1H NMR (500 MHz, CDCl.sub.3) δ (delta) 8.55 (d, 1H), 8.29 (s, 1H), 8.17-8.27 (m, 2H), 7.96 (s, 1H), 7.81-7.92 (m, 1H), 7.45 (dd, 1H), 7.37 (s, 2H), 3.59-3.74 (m, 2H), 3.57 (s, 3H), 3.04-3.14 (m, 1H), 2.87 (dd, 1H), 2.42 (dd, 1H), 2.25-2.38 (m, 1H), 2.22 (s, 6H), 1.72-1.90 (m, 1H).

Step Two: Synthesis of N-[2-[3-[4-(4-cyanopyrazol-1-yl)-2,6-dimethyl-phenyl]-2,4-dioxo-cyclopentyl]ethyl]pyridine-2-carboxamide (compound A142)

(94) ##STR00084##

(95) Prepared according to the same procedure used to prepare A1 (step 5) to give the desired product (26 mg, 96%) as a colourless glass. .sup.1H NMR (500 MHz, d.sub.4-methanol) δ (delta) 8.84 (s, 1H), 8.62 (br.s, 1H), 8.10 (d, 1H), 8.07 (s, 1H), 7.95 (t, 1H), 7.54 (d, 1H), 7.48 (s, 2H), 3.54-3.68 (m, 2H), 2.99 (dd, 1H), 2.81-2.90 (m, 1H), 2.55 (dd, 1H), 2.20-2.27 (m, 1H), 2.18 (s, 6H), 1.79 (ddt, 1H).

Example 10

Synthesis of Compound A111

(96) ##STR00085##

Step One: Synthesis of N-[2-[3-[4-(3-chlorophenyl)-2,6-dimethyl-phenyl]-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl]pyridine-2-carboxamide

(97) ##STR00086##

(98) N-[2-[3-[2,6-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl]pyridine-2-carboxamide (50 mg, 0.10 mmol) was combined with dicloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) (7.5 mg, 0.010 mmol), tripotassium phosphate (87 mg, 0.41 mmol) and 1-bromo-3-chloro-benzene (29 mg, 0.15 mmol) in a mixture of 1,2-dimethoxyethane (1 mL) and water (0.3 mL) in a microwave vial. The mixture was stirred rapidly and degassed by nitrogen bubbling for 2 min, then the vial was sealed and heated in the microwave at 150° C. for 30 min. The mixture was partitioned between dichloromethane (10 mL) and water (5 mL) and then the mixture was passed through a PTFE frit to collect the dichloromethane extract. This was concentrated under reduced pressure and the residue was purified by flash chromatography over silica using an EtOAc/hexane gradient to give the desired product (32 mg, 66%) as a pink gum. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.55 (d, 1H), 7.17-8.28 (m, 2H), 7.87 (td, 1H), 7.55 (t, 1H), 7.41-7.47 (m, 2H), 7.31-7.37 (m, 1H), 7.27-7.31 (m, 1H), 7.24 (s, 2H), 3.61-3.69 (m, 2H), 3.58 (s, 3H), 3.02-3.10 (m, 1H), 2.87 (dd, 1H), 2.41 (dd, 1H), 2.25-2.36 (m, 1H), 2.21 (s, 6H), 1.72-1.89 (m, 1H).

Step Two: Synthesis of N-[2-[3-[4-(3-chlorophenyl)-2,6-dimethyl-phenyl]-2,4-dioxo-cyclopentyl]ethyl]pyridine-2-carboxamide (compound A111)

(99) ##STR00087##

(100) N-[2-[3-[4-(3-chlorophenyl)-2,6-dimethyl-phenyl]-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl]pyridine-2-carboxamide (30 mg, 0.063) was dissolved in morpholine (0.5 mL, 6 mmol) and the mixture was heated under nitrogen at 105° C. for 75 min. The mixture was cooled to room temperature then partitioned between ether (5 mL) and water (10 mL) and the biphasic mixture was filtered through celite. After separation of the phases the aqueous layer pH was adjusted to 5 by dropwise addition of 2M aqueous hydrochloric acid HCl(aq), then extracted with EtOAc (3×5 mL). The combined EtOAc layers were dried over MgSO.sub.4 and concentrated under reduced pressure. The residue was purified by flash chromatography over silica using an EtOAc/hexane gradient to give the desired product (27 mg, 93%) as a brown gum. .sup.1H NMR (400 MHz, CDCl.sub.3) δ (delta) 8.62 (br.s, 1H), 8.58 (d, 1H), 8.17 (d, 1H), 7.88 (t, 1H), 7.53 (s, 1H), 7.49 (dd, 1H), 7.43 (d, 1H), 7.29-7.36 (m, 1H), 7.28 (s, 1H), 7.24 (s, 2H), 4.01 (br.s, 1H), 3.37-3.57 (m, 1H), 2.81-3.03 (m, 2H), 2.26-2.34 (m, 1H), 2.24 (s, 3H), 2.21 (s, 3H), 2.10 (br.s, 1H), 1.98 (br.s, 1H).

Example 11

Synthesis of Compound A170

(101) ##STR00088##

Step One: Synthesis of N-[2-[3-(4-azido-2,6-dimethyl-phenyl)-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl]pyridine-2-carboxamide

(102) ##STR00089##

(103) To a mixture of sodium azide (63 mg, 0.97 mmol) and N-[2-[3-[2,6-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl]pyridine-2-carboxamide (500 mg, 1.02 mmol) in methanol (5 mL) was added copper (II) acetate (18 mg, 0.10 mmol). The resulting mixture was stirred open to air at 55° C. for 6 h in total then cooled to room temperature. The mixture was partitioned between 0.5M aqueous tetrasodium EDTA (50 mL, 25 mmol) and ethyl acetate (50 mL). The phases were separated and the aqueous layer was extracted with ethyl acetate (2×25 mL). The combined organic layers were washed sequentially with 0.5M aqueous tetrasodium EDTA (25 mL, 12.5 mmol), water (25 mL) then brine (25 mL), then dried over MgSO.sub.4 and concentrated under reduced pressure. The residue was purified by flash chromatography over silica using an EtOAc/hexane gradient to give the desired product (330 mg, 84%) as a pale yellow gum. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.55 (d, 1H), 8.15-8.25 (m, 2H), 7.87 (td, 1H), 7.45 (ddd, 1H), 6.73 (s, 2H), 3.64 (qd, 2H), 3.54 (s, 3H), 2.98-3.07 (m, 1H), 2.84 (dd, 1H), 2.38 (dd, 1H), 2.23-2.33 (m, 1H), 2.13 (s, 6H), 1.72-1.84 (m, 1H).

Step Two: Synthesis of N-[2-[3-[2,6-dimethyl-4-(4-trimethylsilyltriazol-1-yl)phenyl]-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl]pyridine-2-carboxamide

(104) ##STR00090##

(105) A mixture of N-[2-[3-(4-azido-2,6-dimethyl-phenyl)-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl]pyridine-2-carboxamide (93 mg, 0.23 mmol), N,N-diisopropylethylamine (0.13 mL, 0.75 mmol) and cuprous iodide (7 mg, 0.04 mmol) in THF (2 mL) in a microwave vial was degassed by nitrogen bubbling for 2 min. Ethynyl(trimethyl)silane (0.70 mL, 5.0 mmol) was then added and the mixture was heated in the microwave at 120° C. for 45 min. The mixture was concentrated under reduced pressure, then the residue purified by flash chromatography over silica using an EtOAc/hexane gradient to give the desired product (48 mg, 42%) as a pale yellow glass. .sup.1H NMR (400 MHz, CDCl.sub.3) δ (delta) 8.56 (d, 1H), 8.16-8.28 (m, 2H), 7.82-7.93 (m, 2H), 7.45 (dd, 1H), 7.43 (s, 2H), 3.61-3.72 (m, 2H), 3.57 (s, 3H), 3.02-3.13 (m, 1H), 2.88 (dd, 1H), 2.42 (dd, 1H), 2.26-2.37 (m, 1H), 2.23 (s, 6H), 1.78-1.87 (m, 1H), 0.37 (s, 9H).

Step Three: Synthesis of N-[2-[3-[4-(4-chlorotriazol-1-yl)-2,6-dimethyl-phenyl]-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl]pyridine-2-carboxamide

(106) ##STR00091##

(107) N-[2-[3-[2,6-dimethyl-4-(4-trimethylsilyltriazol-1-yl)phenyl]-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl]pyridine-2-carboxamide (61 mg, 0.12 mmol) was combined with N-chlorosuccinimide (97 mg, 0.73 mmol) and silica gel (255 mg, 4.24 mmol) in acetonitrile (1 mL). The mixture was heated under reflux for 90 min, then cooled to room temperature. Celite™ (200 mg) was added and the mixture was dry loaded onto silica and purified by flash chromatography over silica using an EtOAc/hexane gradient to give the desired compound (33 mg, 58%) as a pale yellow gum. .sup.1H NMR (400 MHz, CDCl.sub.3) δ (delta) 8.56 (d, 1H), 8.14-8.31 (m, 2H), 7.91 (s, 1H), 7.88 (td, 1H), 7.46 (ddd, 1H), 7.40 (s, 2H), 3.65 (dd, 2H), 3.58 (s, 3H), 3.03-3.14 (m, 1H), 2.88 (dd, 1H), 2.43 (dd, 1H), 2.27-2.37 (m, 1H), 2.24 (s, 6H), 1.76-1.87 (m, 1H).

Step Four: Synthesis of N-[2-[3-[4-(4-chlorotriazol-1-yl)-2,6-dimethyl-phenyl]-2,4-dioxo-cyclopentyl]ethyl]pyridine-2-carboxamide (compound A170)

(108) ##STR00092##

(109) Prepared according to the same procedure used to prepare A1 (step 5) to give the desired product (33 mg, 100%) as a pale yellow gum. .sup.1H NMR (500 MHz, d4 methanol) δ (delta) 8.61 (d, 1H), 8.58 (s, 1H), 8.09 (d, 1H), 7.94 (t, 1H), 7.52 (dd, 1H), 7.49 (s, 2H), 3.56-3.67 (m, 2H), 3.00 (dd, 1H), 2.83-2.91 (m, 1H), 2.56 (dd, 1H), 2.20-2.28 (m, 1H), 2.18 (s, 6H), 1.74-1.86 (m, 1H).

Example 12

Synthesis of Compound A34

(110) ##STR00093##

Step One: Synthesis of pyridine-2-carbonyl chloride hydrochloride

(111) ##STR00094##

(112) DMF (13 mmol, 0.94 g, 1 mL) was added to a suspension of pyridine-2-carboxylic acid (181.14 mmol, 22.3 g) in thionyl chloride (60 mL) and stirred for 3 hours. The excess thionyl chloride was removed under reduced pressure to give a dark purple solid.

Step Two: Synthesis of (2,3,4,5,6-pentafluorophenyl)pyridine-2-carboxylate

(113) ##STR00095##

(114) To a suspension of pyridine-2-carbonyl chloride hydrochloride (182.8 mmol, 32.54 g) in THF (1000 mL), under nitrogen, was added 2,3,4,5,6-pentafluorophenol (182.8 mmol, 33.65 g) followed by the dropwise addition of N,N-diethylethanamine (548.4 mmol, 55.49 g, 76.4 mL). After stirring at room temperature for 2 hours the solid was filtered off through celite and washed with ethyl acetate, the organic layers were concentrated under reduced pressure to leave a brown oil which was purified by flash chromatography (gradient elution: 0-30% ethyl acetate in hexane). The resulting material was further purified by recrystallization from hexane to give the desired product (42.44 g, 80% over 2 steps) as a white solid. .sup.1H NMR (400 MHz, CDCl.sub.3) δ ppm 7.63 (ddd, 1H), 7.97 (td, 1H), 8.30 (d, 1H), 8.88 (dt, 1H).

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

(115) ##STR00096##

(116) 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, follow'd by N,N′-dimethylenediamine (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 flash 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, Chloroform) δ=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 Four: Synthesis of 2-[3-[4-(4-chloropyrazol-1-yl)-2,6-dimethyl-phenyl]-2-methoxy-4-oxo-cyclopent-2-en-1-yl]acetonitrile

(117) ##STR00097##

(118) 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) (3.0175 mL, 3.0175 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 (2×25 mL). The combined organic layers were filtered through a PTFE frit, dry loaded onto silica and purified by flash 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) δ (delta) ppm 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 Five: Synthesis of N-[2-[3-[4-(4-chloropyrazol-1-yl)-2,6-dimethyl-phenyl]-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl]pyridine-2-carboxamide

(119) ##STR00098##

(120) A glass pressure vessel was charged with Raney Nickel (2400) (45.615 mmol, 4 g) which was washed with distilled water (3×10 mL), and the excess water was decanted off. 2-[3-[4-(4-chloropyrazol-1-yl)-2,6-dimethyl-phenyl]-2-methoxy-4-oxo-cyclopent-2-en-1-yl]acetonitrile (2 g, 5.621 mmol), (2,3,4,5,6-pentafluorophenyl)pyridine-2-carboxylate (2.276 g, 7.870 mmol), and 1,2-dimethoxyethane (20 mL) were then added. The vessel was sealed, purged with nitrogen and then hydrogen, and then stirred vigorously at room temperature under 4 Bar of hydrogen for 3 hours. The reaction was filtered through a pad of celite, dry loaded onto silica and purified by flash chromatography (gradient elution: 10-100% EtOAc in hexane) to give N-[2-[3-[4-(4-chloropyrazol-1-yl)-2,6-dimethyl-phenyl]-4-methoxy-2-oxo-cyclopent-3-en-1-yl]ethyl]pyridine-2-carboxamide (1.939 g, 4.171 mmol, 74.2% yield) as a white solid. .sup.1H NMR (400 MHz, CDCl.sub.3) δ (delta) ppm 1.74-1.87 (m, 1H), 2.21 (s, 6H), 2.26-2.36 (m, 1H), 2.41 (dd, 1H), 2.86 (dd, 1H), 3.01-3.10 (m, 1H), 3.56 (s, 3H), 3.65 (qd, 2H), 7.33 (s, 2H), 7.45 (ddd, 1H), 7.62 (s, 1H), 7.83-7.93 (m, 2H), 8.21 (d, 2H), 8.52-8.59 (m, 1H).

Step Six: Synthesis of N-[2-[3-[4-(4-chloropyrazol-1-yl)-2,6-dimethyl-phenyl]-4-methoxy-2-oxo-cyclopent-3-en-1-yl]ethyl]pyridine-2-carboxamide (compound A34)

(121) ##STR00099##

(122) To a solution of N-[2-[3-[4-(4-chloropyrazol-1-yl)-2,6-dimethyl-phenyl]-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl]pyridine-2-carboxamide (11.2 g, 24.1 mmol) in acetone (112 mL) was added 2N HCl (112 mL), and the reaction was heated to 60° C. for 17 hours. The reaction was allowed to cool to ambient temperature, concentrated in vacuo to remove excess acetone, and the pH adjusted to 4.5 using 2N NaOH. The aqueous layer was extracted with EtOAc (2×250 mL). The combined organic layers were dried over Mg.sub.2SO.sub.4, filtered through a PTFE frit and concentrated to give N-[2-[3-[4-(4-chloropyrazol-1-yl)-2,6-dimethyl-phenyl]-2,4-dioxo-cyclopentyl]ethyl]pyridine-2-carboxamide (10.75 g, 23.84 mmol, 98.76% Yield) as a white solid. .sup.1H NMR (400 MHz, Chloroform) δ=12.56 (br. s., 1H), 8.71 (br. s., 1H), 8.61 (d, 1H), 8.21 (d, 1H), 7.91 (t, 1H), 7.87 (s, 1H), 7.61 (s, 1H), 7.57-7.49 (m, 1H), 7.34 (s, 2H), 4.24-4.09 (m, 1H), 3.46 (br. s., 1H), 3.06-2.84 (m, 2H), 2.26 (s, 3H), 2.22 (s, 3H), 2.20-2.15 (m, 2H), 1.89 (br. s., 1H).

Example 13

Synthesis of Compound A120

(123) ##STR00100##

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

(124) ##STR00101##

(125) To a solution of 3-methoxy-2-(2,4,6-trimethylphenyl)cyclopent-2-en-1-one (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 flash 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) δ (delta) ppm 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

(126) ##STR00102##

(127) 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 flash 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) δ (delta) ppm 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-methoxy-4-oxo-3-(2,4,6-trimethylphenyl)cyclopent-2-en-1-yl]ethylammonium chloride

(128) ##STR00103##

(129) 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 HCl 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 Four: Synthesis of (2,3,4,5,6-pentafluorophenyl) 5-bromopyridine-2-carboxylate

(130) ##STR00104##

(131) To a suspension of 5-bromopyridine-2-carboxylic acid (2.48 mmol, 0.500 g) in dichloromethane (15 mL) at room temperature was added 2,3,4,5,6-pentafluorophenol (3.09 mmol, 0.569 g) then 3-(ethyliminomethyleneamino)-N,N-dimethyl-propan-1-amine hydrochloride (3.09 mmol, 0.593 g). After 2 hours the solvent was removed under reduced pressure and the yellow residue was diluted with ethyl acetate and water. The two resulting phases were separated and the aqueous layered was extracted with ethyl acetate. The combined organic layers were washed with water, sodium bicarbonate (saturated) and brine then dried over MgSO.sub.4. The solvent was removed under reduced pressure to give the desired product (0.894 g, 98%) as a yellow solid. .sup.1H NMR (400 MHz, CDCl.sub.3) δ (delta) ppm 8.92 (d, 1H), 8.16 (s, 1H), 8.07-8.14 (m, 1H).

Step Five: Synthesis of 5-bromo-N-{2-[2-methoxy-4-oxo-3-(2,4,6-trimethylphenyl)cyclopent-2-en-1-yl]ethyl}pyridine-2-carboxamide

(132) ##STR00105##

(133) To a solution of 2-[2-methoxy-4-oxo-3-(2,4,6-trimethylphenyl)cyclopent-2-en-1-yl]ethylammonium trifluoroacetate (7.502 mmol, 2.906 g) in dichloromethane (35 mL) at room temperature was added (2,3,4,5,6-pentafluorophenyl) 5-bromopyridine-2-carboxylate (8.252 mmol, 3.797 g) followed by N,N-diethylethanamine (33.00 mmol, 4.59 mL). After stirring for 3 hours, the solvent was removed under reduced pressure and the crude residue was purified by flash chromatography (gradient elution: 0-85% ethyl acetate in hexane) to give the desired product (3.462 g, 100%) as a brown foam. .sup.1H NMR (400 MHz, CDCl.sub.3) δ (delta) ppm 1.68 (br. s., 1H), 1.78 (dq, 1H), 2.03-2.16 (m, 6H), 2.22-2.38 (m, 4H), 2.82 (dd, 1H), 3.00 (dddd, 1H), 3.52-3.63 (m, 5H), 6.86 (s, 2H), 7.99 (d, 1H), 8.03-8.13 (m, 2H), 8.60 (d, 1H).

Step Six: Synthesis of 5-bromo-N-{2-[2,4-dioxo-3-(2,4,6-trimethylphenyl)cyclopentyl]ethyl}pyridine-2-carboxamide (compound A120)

(134) ##STR00106##

(135) To a solution of 5-bromo-N-{2-[2-methoxy-4-oxo-3-(2,4,6-trimethylphenyl)cyclopent-2-en-1-yl]ethyl}pyridine-2-carboxamide (7.569 mmol, 3.462 g) in acetone (35 mL) was added hydrogen chloride (50 mmol, 25 mL) then the mixture was heated to 65° C. overnight. After cooling to room temperature, the acetone was concentrated under reduced pressure and the resulting yellow solution was extracted with dichloromethane. The organic fractions were concentrated under reduced pressure and purified by flash chromatography (gradient elution: 0-100% ethyl acetate in hexane) to give the desired product (3.18 g, 94%) as a white foam. .sup.1H NMR (400 MHz, CDCl.sub.3) δ (delta) ppm 1.6-2.25 (m, 11H), 2.74-3.11 (m, 2H), 3.45 (br. s., 1H), 3.52 (m, 1H), 3.97 (br. s., 1H), 6.84 (br. s., 2H), 7.85-8.15 (m, 2H), 8.48-8.7 (m, 2H).

Example 14

Synthesis of Compound P12

(136) ##STR00107##

(137) To a stirred solution of 5-bromo-N-{2-[2,4-dioxo-3-(2,4,6-trimethylphenyl)cyclopentyl]ethyl}pyridine-2-carboxamide (0.11 mmol, 0.050 g) in dichloromethane (2 mL) at room temperature was added N,N-diethylethanamine (0.12 mmol, 0.013 g) followed by pentanoyl chloride (0.12 mmol, 0.014 g, 0.014 mL). The mixture was left to stir overnight. The reaction mixture was directly purified by flash chromatography (gradient elution: 0-80% ethyl acetate in hexane) to give the desired product (47 mg, 79%) as a colourless oil. .sup.1H NMR (400 MHz, CDCl.sub.3) δ (delta) ppm 0.82 (t, 3H), 1.10-1.31 (m, 2H), 1.43-1.58 (m, 2H), 1.78-1.93 (m, 1H), 1.96-2.11 (m, 6H), 2.14-2.41 (m, 6H), 2.67-2.92 (m, 2H), 3.27 (dd, 1H), 3.48-3.88 (m, 2H), 6.86 (s, 2H), 7.90-8.26 (m, 3H), 8.60 (d, 1H).

Example 15

Synthesis of Compound P3

(138) ##STR00108##

(139) To a solution of 5-bromo-N-{2-[2,4-dioxo-3-(2,4,6-trimethylphenyl)cyclopentyl]ethyl}pyridine-2-carboxamide (0.11 mmol, 0.050 g) in DMF (13 mmol, 0.94 g, 1 mL) at room temperature was added potassium carbonate (0.23 mmol, 0.031 g) and 1-chloroethyl methyl carbonate (0.23 mmol, 0.031 g). The mixture was left to stir at room temperature for 4 days. The mixture was diluted with water and extracted with ethyl acetate, the combined organic layers were washed with water and brine and dried over MgSO.sub.4, filtered and concentrated under reduced pressure. The resulting residue was purified by flash chromatography (gradient elution: 0-100% ethyl acetate in hexane) to give the desired product (50 mg, 81%) as a colourless oil. .sup.1H NMR (400 MHz, CDCl3) δ (delta) ppm 8.47-8.70 (m, 1H), 7.88-8.23 (m, 3H), 6.73-6.95 (m, 2H), 5.71-6.32 (m, 1H), 3.52-3.83 (m, 4H), 2.33-3.30 (m, 3H), 2.27 (s, 4H), 1.98-2.10 (m, 6H), 1.67-1.91 (m, 2H), 1.30-1.57 (m, 3H).

Example 16

Synthesis of Compound P22

(140) ##STR00109##

(141) To a solution of 5-bromo-N-{2-[2,4-dioxo-3-(2,4,6-trimethylphenyl)cyclopentyl]ethyl}pyridine-2-carboxamide (0.11 mmol, 0.050 g) in dichloromethane (2 mL) at room temperature in a microwave vial was added pyrrolidine-1-carbonyl chloride (0.23 mmol, 0.030 g) and the phosphazine base, P2tBu (1-tert-butyl-2,2,4,4,4-pentakis(dimethylamino)-2λ.sup.5,4λ.sup.5-catenadi(phosphazene)) (2M in THF, 0.10 mmol, 0.050 mL). The reaction was heated to 100° C. for 30 minutes. The reaction mixture was directly purified by flash chromatography (gradient elution: 0-80% ethyl acetate in hexane) to give the desired product (22 mg, 36%) as a colourless oil. .sup.1H NMR (400 MHz, CDCl3) δ (delta) ppm 1.86 (d, 4H), 2.01-2.14 (m, 6H), 2.26 (s, 4H), 2.67-3.12 (m, 2H), 3.14-3.50 (m, 6H), 3.52-3.84 (m, 2H), 6.86 (s, 2H), 7.85-8.23 (m, 3H), 8.60 (d, 1H).

Example 16A

Synthesis of Compound A126B

(142) ##STR00110##

Step One: Synthesis of N-{2-[3-(4-hydroxy-2,6-dimethyl-phenyl)-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl}pyridine-2-carboxamide

(143) ##STR00111##

(144) An aqueous solution of hydrogen peroxide (1.1 g, 9.7 mmol, 30 mass %) was added to a stirred suspension of N-[2-[3-[2,6-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl]pyridine-2-carboxamide (500 mg, 1.02 mmol) in methanol (10 mL). After 20 hours, a solution of sodium metabisulfite (20 mL, 10 mmol, 0.5 mol/L) was added dropwise to the rapidly-stirred reaction mixture. The methanol was removed under reduced pressure, then the mixture was partitioned with ethyl acetate (20 mL). The phases were separated, then the aqueous layer was extracted with ethyl acetate (2×10 mL). The combined organic extracts were washed with brine (10 mL), then dried over MgSO.sub.4 and concentrated under reduced pressure. The residue was purified by flash chromatography over silica using an EtOAc/hexane gradient to give the desired product (360 mg, 93%) as a white foam. .sup.1H NMR (400 MHz, CDCl.sub.3) δ (delta) 8.49-8.61 (m, 1H), 8.15-8.28 (m, 2H), 7.8 (td, 1H), 7.44 (dddd, 1H), 6.44 (s, 1H), 3.60-3.69 (m, 2H), 3.53 (s, 3H), 3.01 (dddd, 1H), 2.85 (dd, 1H), 2.39 (dd, 1H), 2.22-2.32 (m, 1H), 2.03 (s, 6H), 1.73-1.84 (m, 1H).

Step Two: Synthesis of N-[2-[3-[4-[[3-chloro-5-(trifluoromethyl)-2-pyridyl]oxy]-2,6-dimethyl-phenyl]-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl]pyridine-2-carboxamide

(145) ##STR00112##

(146) N-{2-[3-(4-hydroxy-2,6-dimethyl-phenyl)-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl}pyridine-2-carboxamide (101 mg, 0.266 mmol) was combined with 3-chloro-2-fluoro-5-(trifluoromethyl)pyridine (66 mg, 0.33 mmol) and potassium carbonate (74 mg, 0.53 mmol) in dimethyl sulfoxide (1 mL). The mixture was heated at 60° C. with stirring for 30 min then cooled to room temperature. The mixture was partitioned between ethyl acetate (15 mL) and water (10 mL). The phases were separated and the aqueous layer was extracted with ethyl acetate (5 mL). The combined organic layers were washed with water (2×5 mL), then brine (5 mL), then filtered through a PTFE frit and concentrated under reduced pressure. The residue was purified by flash chromatography over silica using an EtOAc/hexane gradient to give the desired product (141 mg, 95%) as a colourless gum. .sup.1H NMR (400 MHz, CDCl.sub.3) δ (delta) 8.56 (d, 1H), 8.17-8.25 (m, 2H), 7.96 (d, 1H), 7.87 (td, 1H), 7.45 (ddd, 1H), 6.87 (s, 2H), 3.65 (qd, 2H), 3.59 (s, 3H), 3.05 (dddd, 1H), 2.85 (dd, 1H), 2.40 (dd, 1H), 2.25-2.36 (m, 1H), 2.16 (s, 6H), 1.73-1.85 (m, 1H).

Step Three: Synthesis of N-[2-[3-[4-[[3-chloro-5-(trifluoromethyl)-2-pyridyl]oxy]-2,6-dimethyl-phenyl]-2,4-dioxo-cyclopentyl]ethyl]pyridine-2-carboxamide (compound A126B)

(147) ##STR00113##

(148) The above compound was prepared from N-[2-[3-[4-[[3-chloro-5-(trifluoromethyl)-2-pyridyl]oxy]-2,6-dimethyl-phenyl]-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl]pyridine-2-carboxamide, according a procedure substantially similar to that used to prepare compound A1 (Example 1, step 5) to give the desired product (103 mg, 91%) as a colourless foam. 1H NMR (400 MHz, CDCl.sub.3) δ (delta) 8.69 (br.s, 1H), 8.60 (br.s, 1H), 8.27 (br.s, 1H), 8.22 (d, 1H), 7.87-7.99 (m, 2H), 7.52 (br.s, 1H), 6.87 (s, 2H), 4.13 (d, 1H), 3.45 (d, 1H), 2.98 (br.s, 1H), 2.89 (dd, 1H), 2.10-2.29 (m, 8H), 1.91 (t, 1H).

Example 16B

Synthesis of Compound P1

(149) ##STR00114##

Step One: 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

(150) ##STR00115##

(151) 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 A120 (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) δ (delta) 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 Two: Synthesis of 2-[3-[4-(4-chloropyrazol-1-yl)-2,6-dimethyl-phenyl]-2,4-dioxo-cyclopentyl]ethylammonium chloride (Intermediate 3)

(152) ##STR00116##

(153) 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 (Intermediate 3) (0.085 g, 99%) as an off white glass. .sup.1H NMR (500 MHz, D.sub.2O) δ (delta) ppm 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).

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

Step Three: Synthesis of [2-[4-(4-chloropyrazol-1-yl)-2,6-dimethyl-phenyl]-4-[2-[(5-chloropyridine-2-carbonyl)amino]ethyl]-3-oxo-cyclopenten-1-yl]5-chloropyridine-2-carboxylate (compound P1)

(155) ##STR00117##

(156) To a solution of 2-[3-[4-(4-chloropyrazol-1-yl)-2,6-dimethyl-phenyl]-2,4-dioxo-cyclopentyl]ethylammonium chloride (e.g. Intermediate 3) (0.172 mmol, 0.066 g) in dichloromethane (5 mL) was added triethylamine (1.7 mmol, 0.98 mL) and 5-chloropyridine-2-carbonyl chloride (1.1 mmol, 0.19 g). After stirring for 1 hour at room temperature the reaction was absorbed onto silica and purified by flash chromoatography (gradient elution: 0-100% ethyl acetate in hexane) to give the desired product (0.059 g, 55%) as an orange oil. .sup.1H NMR (500 MHz, CDCl.sub.3) δ (delta) ppm 8.39-8.74 (m, 2H), 8.04-8.23 (m, 2H), 7.48-7.98 (m, 5H), 7.20-7.42 (m, 2H), 3.32-3.88 (m, 3H), 2.88-3.21 (m, 2H), 2.06-2.37 (m, 7H), 1.84-2.00 (m, 1H).

Intermediate 4

Synthesis of 2-[3-(2,4,6-trimethyl-phenyl)-2,4-dioxo-cyclopentyl]ethylammonium chloride

(157) ##STR00118##

(158) Using similar procedures to those described in Example 16B steps 1 and 2 to prepare Intermediate 3, the above-shown intermediate compound (Intermediate 4) can be prepared from tert-butyl N-{2-[3-(2,4,6-trimethyl-phenyl)-2-methoxy-4-oxo-cyclopent-2-en-1-yl]ethyl}carbamate.

(159) Note: The above-shown HCl salt of the amine (R—NH.sub.3.sup.+Cl.sup.−) (Intermediate 4) can optionally be converted to the corresponding free amine (R—NH.sub.2) if desired, e.g. via an ion exchange column.

FURTHER CHIRAL HPLC EXAMPLES

Example 17

Neutralization and the Removal of Trifluoroacetate Salt Introduced into A98 During Chiral HPLC

(160) N-[2-[(1R)-3-[4-(4-chloropyrazol-1-yl)-2,6-dimethyl-phenyl]-2,4-dioxo-cyclopentyl]ethyl]pyridinium-2-carboxamide trifluoroacetate (54.36 g) was suspended in water (500 mL) and EtOAc (50 mL). Sodium bicarbonate was carefully added portionwise to the mixture until pH 5.0 was achieved. The solution was extracted with EtOAc (500 mL). The aqueous layer was re-acidified to pH 5.0 using 2N HCl and extracted with EtOAc (500 mL). The combined organic layers were dried over MgSO.sub.4, filtered through a PTFE frit and concentrated in vacuo to give beige solid N-[2-[(1R)-3-[4-(4-chloropyrazol-1-yl)-2,6-dimethyl-phenyl]-2,4-dioxo-cyclopentyl]ethyl]pyridine-2-carboxamide (43.63 g, 96.76 mmol).

Example 18

Chiral HPLC Separation of Enantiomers of Compound A120 (to Compounds A120A and A120B)

(161) ##STR00119##

(162) Compound A120 (racemic), was separated into the enantiomer compounds A120A and A120B and using a chiral SFC column, by the following method and under the following conditions.

(163) The chiral SFC column used was a Chiralpak® AD—5 micron—20 mm×250 mm SFC column, manufactured by Daicel. In this column, the chiral stationary phase is amylose tris(3,5-dimethylphenylcarbamate)

(164) The solvent system used as an eluent for the column was a 30:70 (by volume) mixture of Solvent A and Solvent B, in which: Solvent A is methanol Solvent B is supercritical carbon dioxide.

(165) Other conditions were as follows: Flow rate through column: 50 ml/minute. Loading (compound loaded onto column): 20 mg/ml in methanol:acetonitrile (50:50). Volume of sample (compound) injected per run=1.0 ml Number of injections of compound=17. Length of run=6 minutes Detection wavelength=245 nm

(166) Chiral SFC on a total of 340 mg of compound A120 under the above conditions gave 126 mg of compound A120A (100% enantiomeric excess (e.e.), retention time 2.57 minutes under the above conditions) and 84 mg of compound A120B (98.5% enantiomeric excess (e.e.), retention time 3.18 minutes under the above conditions).

(167) Abbreviation: SFC=Supercritical fluid chromatography

Example 19

Chiral HPLC Separation of Enantiomers of Compound A23 (to Compounds A127 and A128)

(168) ##STR00120##

(169) Compound A23 (racemic), was separated into the enantiomer compounds A127 and A128 using a chiral HPLC column, by the following method and under the following conditions.

(170) The chiral HPLC column used was a (s,s)WhelkO1—5 micron—20 mm×250 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.

(171) The solvent system used as an eluent for the column was a 50:50 (by volume) mixture of Solvent A and Solvent B, in which: Solvent A is isohexane containing 1.0% v/v of isopropanol and 0.1% v/v of trifluoroacetic acid (TFA), and Solvent B is an 80:20 v/v mixture of ispropanol:methanol

(172) Other conditions were as follows: Flow rate through column: 50 ml/minute. Loading (compound loaded onto column): 53 mg/ml in isopropanol. Volume of sample (compound) injected per run=1.0 ml Number of injections of compound=6 Length of run=15 minutes

(173) Chiral HPLC on a total of 320 mg of compound A23 under the above conditions gave 186 mg of the trifluoroacetate salt of compound A127 (100% enantiomeric excess (e.e.), retention time 9.31 minutes under the above conditions) and 192 mg of the trifluoroacetate salt of compound A128 (99.7% enantiomeric excess (e.e.), retention time 12.11 minutes under the above conditions).

Example 20

Chiral HPLC Separation of Enantiomers of Compound A89 (to Compounds A112 and A113)

(174) ##STR00121##

(175) Compound A89 (racemic), was separated into the enantiomer compounds A112 and A113 using a chiral HPLC column, by the following method and under the following conditions.

(176) The chiral HPLC column used was a (s,s)WhelkO1—5 micron—20 mm×250 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.

(177) The solvent system used as an eluent for the column was a 40:60 (by volume) mixture of Solvent A and Solvent B, in which: Solvent A is isohexane Solvent B is isopropanol

(178) Other conditions were as follows: Flow rate through column: 23 ml/minute from 0 to 14 minutes increasing to 27 ml/minute from 14.5 minutes to the end of the run. Loading (compound loaded onto column): 40 mg/ml in isopropanol. Volume of sample (compound) injected per run=0.4 ml Number of injections of compound=16 Length of run=20 minutes

(179) Chiral HPLC on a total of 400 mg of compound A89 under the above conditions gave 111 mg of compound A112 (98.8% enantiomeric excess (e.e.), retention time 8.07 minutes under the above conditions) and 97 mg of compound A113 (98.4% enantiomeric excess (e.e.), retention time 9.75 minutes under the above conditions).

(180) Additional compounds in Tables A1, A2 and A3 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 and with any appropriate and/or necessary process changes. It should be noted that certain compounds of the invention exist as a mixture of isomers, including atropisomers, 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 NMR spectra were recorded at ambient temperature.

(181) TABLE-US-00011 TABLE A1 Compound No. Structure Data A1 .sup.1H NMR (400 MHz, d4-Methanol) δ (delta) 7.86-7.80 (m, 2H), 7.56- 7.50 (m, 1H), 7.49-7.42 (m, 2H), 6.86 (s, 2H), 3.55 (t, 2H), 2.95 (dd, 1H), 2.85-2.76 (m, 1H), 2.49 (dd, 1H), 2.24 (s, 3H), 2.22-2.13 (m, 1H), 2.04 (s, 6H), 1.74 (tdd, 1H). A2 1H NMR (400 MHz, d-4 methanol) δ (delta) 6.85 (s, 2H), 3.35-3.30 (m, 2H), 2.90 (dd, 1H), 2.75-2.70 (m, 1H), 2.40 (d, 1H), 2.25 (s, 3H), 2.05 (s, 6H), 2.05-2.00 (m, 1H), 1.65-1.55 (m, 1H), 1.20 (s, 9H) A3 1H NMR (400 MHz, d-4 methanol) δ (delta) 8.65 (d, 1H), 8.10 (d, 1H), 7.95 (dd, 1H), 7.55 (dd, 1H), 6.85 (s, 2H), 3.65-3.55 (m, 2H), 2.90 (dd, 1H), 2.80-2.75 (m, 1H), 2.50 (d, 1H), 2.25 (s, 3H), 2.25-2.20 (m, 1H), 2.05 (s, 6H), 1.80-1.70 (m, 1H) A4 1H NMR (400 MHz, d-4 methanol) δ 8.05 (s, 1H), 7.50 (d, 1H), 7.45 (d, 1H), 6.85 (s, 2H), 3.55-3.50 (m, 2H), 2.90 (dd, 1H), 2.80-2.75 (m, 1H), 2.45 (d, 1H), 2.25 (s, 3H), 2.20- 2.15 (m, 1H), 2.05 (s, 6H), 1.75- 1.70 (m, 1H) A5 1H NMR (400 MHz, d-4 methanol) δ (delta) 7.70 (d, 1H), 7.65 (d, 1H), 7.25-7.20 (m, 1H), 6.85 (s, 2H), 3.55-3.50 (m, 2H), 2.95 (dd, 1H), 2.80-2.75 (m, 1H), 2.45 (dd, 1H), 2.25 (s, 3H), 2.20-2.15 (m, 1H), 2.05 (s, 6H), 1.75-1.70 (m, 1H) A6 1H NMR (400 MHz, d-4 methanol) δ 7.55 (s, 1H), 7.45 (d, 1H), 7.40 (d, 1H), 6.85 (s, 2H), 3.60-3.45 (m, 2H), 2.95 (dd, 1H), 2.85-2.80 (m, 1H), 2.50 (d, 1H), 2.25 (s, 3H), 2.25- 2.15 (m, 1H), 2.05 (s, 6H), 1.75- 1.65 (m, 1H) A7 1H NMR (400 MHz, d-4 methanol) δ (delta) 1.65-1.75 (1H, m), 2.02- 2.06 (6H, s), 2.11-2.21 (1H, m), 2.23-2.26 (3H, s), 2.44-2.51 (1H, m), 2.73-2.81 (1H, m), 2.88-2.97 (1H, m), 3.47-3.54 (2H, m), 6.55-6.57 (1H, m), 6.84-6.87 (2H, s), 7.08-7.12 (1H, m), 7.63-7.66 (1H, m) A8 1H NMR (400 MHz, d-4 methanol) δ (delta) 1.56-1.68 (2H, m), 1.82- 1.93 (1H, m), 1.94-2.11 (8H, m), 2.11-2.21 (1H, m), 2.22-2.34 (5H, m), 2.41-2.49 (1H, m), 2.70- 2.79 (1H, m), 2.87-2.96 (1H, m), 3.07-3.17 (1H, m), 3.31- 3.38 (2H, m), 6.87-6.91 (2H, s) A9 0 1H NMR (400 MHz, d-4 methanol) δ (delta) 1.54-1.65 (3H, m), 1.66- 1.79 (4H, m), 1.81-1.91 (2H, m), 2.00-2.10 (7H, m), 2.22-2.26 (3H, s), 2.39-2.46 (1H, m), 2.57-2.66 (1H, m), 2.67-2.76 (1H, m), 2.84-2.92 (1H, m), 3.28-3.35 (2H, m), 6.84-6.88 (2H, s) A10 1H NMR (400 MHz, d-4 methanol) δ (delta) 1.13-1.19 (3H, t), 1.57- 1.69 (1H, m), 2.03-2.14 (7H, m), 2.20-2.30 (5H, m), 2.42-2.50 (1H, m), 2.72-2.80 (1H, m), 2.88- 2.96 (1H, m), 3.32-3.39 (2H, m), 6.88-6.91 (2H, s) A11 1H NMR (400 MHz, d-4 methanol) δ (delta) 1.72-1.82 (1H, m), 2.02- 2.06 (6H, d), 2.11-2.22 (1H, m), 2.22- 2.26 (3H, s), 2.46-2.53 (1H, m), 2.78- 2.86 (1H, m), 2.89-2.97 (1H, m), 3.51-3.65 (2H, m), 3.92-3.95 (3H, s), 6.84-6.88 (2H, s), 7.01-7.07 (1H, t), 7.10-7.14 (1H, d), 7.45-7.51 (1H, m), 7.85-7.90 (1H, m) A12 1H NMR (400 MHz, d4-methanol) δ (delta) 1.72-1.84 (1H, m), 2.05- 2.10 (6H, s), 2.17-2.30 (4H, m), 2.49- 2.57 (1H, m) 2.80-2.88 (1H, m), 2.94- 3.03 (1H, m), 3.57-3.63 (2H, t), 6.87- 6.92 (2H, s), 7.78-7.83 (2H, d), 8.01- 8.06 (2H, d) A13 1H NMR (400 MHz, d-4 methanol) δ (delta) 1.20-1.50 (5H, m), 1.53- 1.64 (1H, m), 1.65-1.72 (1H, m), 1.75-1.83 (4H, m), 1.99-2.09 (7H, m), 2.12-2.22 (1H, m), 2.23- 2.26 (3H, s), 2.37-2.44 (1H, m), 2.66-2.75 (1H, m), 2.83- 2.91 (1H, m), 3.28-3.34 (2H, m), 6.84-6.87 (2H, s). A14 1H NMR (400 MHz, d-4 methanol) δ 1.67-1.78 (1H, m), 2.03-2.06 (6H, s), 2.12-2.22 (1H, m), 2.22- 2.26 (3H, s), 2.44-2.52 (1H, m), 2.74-2.82 (1H, m), 2.89- 2.98 (1H, m), 3.50-3.57 (2H, t), 6.84-6.88 (2H, s), 7.30-7.37 (1H, t), 7.80-7.85 (1H, m), 7.97- 8.01 (1H, m) A15 1H NMR (400 MHz, d-4 methanol) δ (delta) 1.69-1.80 (1H, m), 2.02- 2.07 (6H, s), 2.13-2.23 (1H, m), 2.23- 2.27 (3H, s), 2.46-2.53 (1H, m), 2.76- 2.84 (1H, m), 2.90-2.99 (1H, m), 3.52-3.58 (2H, t), 6.84-6.88 (2H, s), 7.33-7.39 (2H, d), 7.91-7.97 (2H, m) A16 1H NMR (400 MHz, d-4 methanol) δ (delta) 1.65-1.75 (1H, m), 2.02- 2.06 (6H, s), 2.09-2.21 (1H, m), 2.22- 2.26 (3H, s), 2.43-2.51 (1H, m), 2.72-2.82 (1H, m), 2.88-2.97 (1H, m), 3.45-3.52 (2H, t), 6.78-6.81 (1H, m), 6.84-6.87 (2H, s), 7.54-7.57 (1H, m), 8.04-8.06 (1H, m) A17 1H NMR (400 MHz, d-4 methanol) δ (delta) 1.66-1.77 (1H, m), 2.02- 2.07 (6H, s), 2.13-2.23 (1H, m), 2.23-2.26 (3H, s), 2.45-2.53 (1H, m), 2.76-2.84 (1H, m), 2.89- 2.98 (1H, m), 3.51-3.58 (2H, m), 6.84-6.88 (2H, s), 7.03- 7.11 (2H, m), 7.75-7.83 (1H, m) A18 1H NMR (400 MHz, d-4 methanol) δ (delta) 1.68-1.78 (1H, m), 2.02- 2.06 (6H, s), 2.11-2.21 (1H, m), 2.23-2.26 (3H, s), 2.44-2.51 (1H, m), 2.74-2.83 (1H, m), 2.88- 2.97 (1H, m), 3.50-3.56 (2H, t), 3.82-3.86 (3H, s), 6.84- 6.88 (2H, s), 6.95-6.70 (2H, m), 7.78-7.84 (2H, m) A19 0 1H NMR (400 MHz, d-4 methanol) δ (delta) 1.68-1.79 (1H, m), 2.02- 2.06 (6H, s), 2.12-2.22 (1H, m), 2.22-2.26 (3H, s), 2.45-2.53 (1H, m), 2.75-2.84 (1H, m), 2.90- 2.99 (1H, m), 3.50-3.57 (2H, t), 6.84-6.88 (2H, s), 7.14- 7.22 (2H, m), 7.86-7.92 (2H, m) A20 1H NMR (400 MHz, d-chloroform) δ (delta) broad signals 1.87-2.10 (8H, m), 2.21-2.27 (3H, s), 2.38-2.48 (1H, d), 2.94-3.07 (2H, m), 3.42-3.54 (1H, m), 3.71-3.83 (1H, m), 6.82-6.87 (2H, s), 7.25-7.41 (2H, m), 7.52-7.66 (2H, m) A21 (As a mixture of diastereoisomers) .sup.1H NMR (400 MHz, d4-methanol) δ (delta) 0.99-1.01 (3H, m), 1.17 (1H, t), 1.50-1.83 (3H, m), 2.00 (3H, s), 2.04 (3H, s), 2.11-2.20 (1H, m), 2.24 (3H, s), 2.45-2.55 (1H, m), 2.80- 2.90 (1H, m), 3.55-3.65 (1H, m), 4.10-4.25 (1H, m), 6.82-6.87 (2H, m), 7.16-7.23 (2H, m), 7.88-7.95 (2H, m). A22 1H NMR (400 MHz, d-4 methanol) δ (delta) 1.68-1.80 (1H, m), 2.01- 2.06 (6H, s), 2.13-2.22 (1H, m), 2.22- 2.26 (3H, s), 2.45-2.53 (1H, m), 2.76- 2.84 (1H, m), 2.90-2.99 (1H, m), 3.52-3.58 (2H, t), 6.83-6.88 (2H, s), 7.52-7.57 (1H, d), 8.17-8.23 (1H, m), 8.78-8.82 (1H, d) A23 1H NMR (400 MHz, d-4 methanol) δ (delta) 1.68-1.80 (1H, m), 2.02- 2.06 (6H, s), 2.14-2.26 (4H, m), 2.45-2.53 (1H, m), 2.76-2.84 (1H, m), 2.89-2.97 (1H, m), 3.55- 3.62 (2H, m), 6.84-6.87 (2H, s), 7.59-7.63 (1H, m), 8.08-8.11 (1H, d), 8.55-8.59 (1H, d) A24 1H NMR (400 MHz, d-4 methanol) δ (delta) 1.66-1.77 (1H, m), 2.02- 2.07 (6H, s), 2.14-2.27 (4H, m), 2.46-2.53 (1H, m), 2.79-2.88 (1H, m), 2.90-2.99 (1H, m), 3.50- 3.56 (2H, m), 6.85-6.88 (2H, s), 7.48-7.52 (1H, d), 7.88-7.92 (1H, d) A25 1H NMR (400 MHz, d-4 methanol) δ (delta) 1.67-1.78 (1H, m), 2.02- 2.06 (6H, d), 2.12-2.22 (1H, m), 2.23-2.26 (3H, s), 2.44-2.51 (1H, m), 2.75-2.83 (1H, m), 2.90- 2.98 (1H, m), 3.51-3.56 (2H, m), 6.84-6.88 (2H, s), 7.77-7.79 (1H, s), 7.88-7.90 (1H, s) A26 1H NMR (400 MHz, d4-methanol) δ (delta) 1.67-1.78 (1H, m), 2.03- 2.07 (6H, s), 2.15-2.26 (4H, m), 2.46-2.54 (1H, m), 2.79-2.90 (1H, m), 2.91-3.00 (1H, m), 3.49- 3.58 (2H, m), 6.85-6.88 (2H, s), 7.43-7.47 (1H, m), 7.89- 7.93 (1H, m), 8.42-8.45 (1H, m). A27 1H NMR (400 MHz, d4-methanol) δ (delta) 1.75-1.86 (1H, m), 2.02- 2.07 (6H, m), 2.21-2.31 (4H, m), 2.50-2.57 (1H, m), 2.82-2.90 (1H, m), 2.92-3.00 (1H, m), 3.62-3.70 (2H, m), 6.83-6.88 (2H, s), 7.64-7.71 (1H, t), 7.78-7.85 (1H, t), 7.96-8.01 (1H, d), 8.14-8.22 (2H, t), 8.44-8.49 (1H, d). A28 1H NMR (400 MHz, d4-methanol) δ (delta) 1.66-1.77 (1H, m), 2.02- 2.06 (6H, m), 2.11-2.22 (1H, m), 2.22-2.27 (3H, s), 2.43-2.52 (1H, m), 2.73-2.83 (1H, m), 2.88- 2.98 (1H, m), 3.49-3.55 (2H, m), 3.99 (3H, s), 6.86 (2H, s), 7.10 (1H, d), 7.33 (1H, d). A29 0 1H NMR (400 MHz, d4-methanol) δ (delta) 1.65-1.78 (1H, m), 2.02- 2.07 (6H, m), 2.11-2.22 (1H, m), 2.22-2.26 (3H, s), 2.43-2.52 (1H, m), 2.72-2.83 (1H, m), 2.88- 2.98 (1H, m), 3.49-3.55 (2H, t), 6.84-6.88 (2H, s), 7.08-7.11 (1H, s), 7.32-7.35 (1H, s), 7.88-7.90 (1H, s). A32 1H NMR (400 MHz, d4-methanol) δ (delta) 1.75-1.89 (1H, m), 2.13- 2.18 (6H, s), 2.20-2.32 (1H, m), 2.50- 2.60 (1H, m), 2.83-2.93 (1H, m), 2.97-3.09 (1H, m), 3.64-3.70 (2H, t), 7.08-7.16 (2H,t), 7.22-7.26 (2H, s), 7.53-7.60 (2H, m), 8.11-8.18 (1H, t), 8.54-8.61 (1H, m), 8.63-8.71 (1H, t), 8.84-8.90 (1H, bd). A33 1H NMR (400 MHz, d4-methanol) δ (delta) 1.69-1.82 (1H, m), 1.96- 2.00 (3H, s), 2.01-2.09 (6H, s), 2.13-2.25 (1H, m), 2.46-2.55 (1H, m), 2.76-2.85 (1H, m), 2.90- 2.99 (1H, m), 3.56-3.63 (2H, m), 7.02-7.07 (2H, s), 7.50-7.57 (1H, m), 7.91-7.98 (1H, t), 8.05-8.13 (1H, m), 8.59-8.66 (1H, m). A34 1H NMR (400 MHz, CDCl.sub.3) δ (delta) 1.85-1.95 (1H, m), 2.18-2.21 (6H, s), 2.21-2.29 (3H, m), 2.87-3.05 (2H, m), 3.40-3.52 (1H, m), 7.34-7.38 (2H, m), 7.51-7.58 (1H, m), 7.61-7.64 (1H, s), 7.87-7.90 (1H, s), 7.90-7.97 (1H, t), 8.21-8.26 (1H, d), 8.61-8.65 (1H, d), 8.70-8.77 (1H, m) A35 1H NMR (400 MHz, d4-methanol) δ (delta) 1.61-1.87 (5H, m), 2.04- 2.13 (6H, m), 2.25-2.30 (3H, m), 2.49-2.88 (3H, m), 2.96-3.05 (1H, m), 3.14-3.23 (1H, m), 3.35- 3.51 (4H, m), 3.89-4.01 (2H, m), 6.86-6.93 (2H, m) A36 1H NMR (400 MHz, d4-methanol) δ (delta) 1.59-1.72 (1H, m), 2.02- 2.20 (8H, m), 2.25-2.30 (3H, s), 2.47-2.54 (1H, m), 2.65-2.76 (1H, m), 2.77-2.86 (1H, m), 2.94- 3.22 (2H, m), 3.35-3.42 (2H, m), 3.74-4.00 (4H, m), 6.86- 6.93 (2H, m) A37 11H NMR (400 MHz, d4-methanol) δ (delta) 1.74-1.86 (1H, m), 2.10- 2.20 (6H, s), 2.21-2.32 (4H, m), 2.46- 2.57 (1H, m), 2.82-2.88 (1H, m), 2.90-2.98 (1H, m), 3.62-3.72 (2H, t), 6.85-6.88 (2H, s), 7.58-7.70 (2H, m), 8.33-8.42 (2H, m) A38 1 H NMR (400 MHz, d4-methanol) δ (delta) 1.73-1.85 (1H, m), 2.16- 2.28 (7H, m), 2.50-2.59 (1H, m), 2.81-2.89 (1H, m), 2.93-3.03 (1H, m), 3.56-3.66 (2H, m), 7.48- 7.62 (1H, bs), 7.64-7.68 (2H, s), 7.81-7.89 (2H, m), 7.93-7.99 (1H, t), 8.01-8.18 (1H, bs), 8.54-8.58 (1H, s), 8.58-8.71 (1H, bs). A39 1H NMR (400 MHz, d4-methanol) δ (delta) 1.65-1.77 (1H, m), 2.01- 2.07 (6H, s), 2.14-2.26 (4H, m), 2.45-2.54 (1H, m), 2.77-2.86 (1H, m), 2.89-2.99 (1H, m), 3.44- 3.62 (2H, m), 6.81-6.88 (2H, s), 7.48-7.54 (1H, d), 7.88-7.94 (1H, d), A40 1H NMR (400 MHz, d4-methanol) δ (delta) 1.66-1.77 (1H, m), 2.03- 2.07 (6H, s), 2.16-2.26 (4H, m), 2.47- 2.54 (1H, m), 2.81-2.88 (1H, m), 2.91-2.99 (1H, m), 3.47-3.63 (2H, m), 6.84-6.88 (2H, s), 7.43- 7.47 (1H, d), 8.08-8.12 (1H, d) A41 0 1H NMR (400 MHz, d4-methanol) δ (delta) 1.68-1.79 (1H, m), 2.02- 2.06 (6H, s), 2.12-2.22 (1H, m), 2.22- 2.26 (3H, s), 2.45-2.52 (1H, m), 2.78- 2.85 (1H, m), 2.88-2.97 (1H, m), 3.51-3.57 (2H, t), 6.84-6.87 (2H, s), 7.18-7.26 (2H, m), 7.84-7.86 (1H, m) A43 1H NMR (400 MHz, d4-methanol) δ (delta) 1.71-1.82 (1H, m), 2.05- 2.12 (6H, s), 2.20-2.31 (4H, m), 2.51-2.59 (1H, m), 2.84-2.92 (1H, m), 2.94-3.03 (1H, m), 3.53- 3.69 (2H, m), 6.87-6.92 (2H, s), 8.38-8.41 (1H, s), 8.86-8.90 (1H, s) A44 1H NMR (400 MHz, d4-methanol) δ (delta) 1.67-1.78 (1H, m), 2.03- 2.07 (6H, s), 2.16-2.27 (4H, m), 2.47-2.55 (1H, m), 2.81-2.90 (1H, m), 2.91-2.99 (1H, m), 3.49- 3.64 (2H, m), 6.84-6.88 (2H, s), 7.47-7.52 (1H, m), 7.94-7.98 (1H, m), 8.50-8.54 (1H, m) A45 1H NMR (400 MHz, d4-methanol) δ (delta) 1.59-1.71 (1H, m), 2.01- 2.16 (7H, m), 2.22-2.36 (3H, s), 2.39-2.47 (1H, m), 2.73-2.80 (1H, m), 2.86-2.95 (1H, m), 3.36- 3.43 (2H, m), 4.87-4.94 (2H, s), 6.84-6.88 (2H, s), 7.94-7.99 (2H, m), 8.51-8.57 (1H, m), 8.72- 8.77 (1H, m) A46 1H NMR (400 MHz, d4-methanol) δ (delta) 1.71-1.81 (1H, m), 2.06- 2.10 (6H, s), 2.20-2.31 (4H, m), 2.51-2.58 (1H, m), 2.86-2.93 (1H, m), 2.96-3.03 (1H, m), 3.52- 3.67 (2H, m), 6.88-6.91 (2H, s), 7.41-7.46 (1H, m), 8.14-8.18 (1H, m), 8.56-8.59 (1H, m) A47 1H NMR (400 MHz, d4-methanol) δ (delta) 1.67-1.78 (1H, m), 2.02- 2.06 (6H, s), 2.15-2.27 (4H, m), 2.45-2.52 (1H, m), 2.75-2.83 (1H, m), 2.89-2.97 (1H, m), 3.51- 3.64 (2H, m), 6.83-6.87 (2H, s), 7.58-7.62 (1H, m), 7.93-7.99 (1H, t), 8.03-8.07 (1H, d) A48 1H NMR (400 MHz, d4-methanol) δ (delta) 1.67-1.78 (1H, m), 2.02- 2.06 (6H, s), 2.14-2.26 (4H, m), 2.45-2.52 (1H, m), 2.76-2.83 (1H, m), 2.89-2.97 (1H, m), 3.51- 3.64 (2H, m), 6.83-6.87 (2H, m), 7.72-7.77 (1H, d), 7.82-7.88 (1H, t), 8.06-8.09 (1H, d) A50 1H NMR (400 MHz, d4-methanol) δ (delta) 1.57-1.68 (1H, m), 2.01- 2.05 (6H, d), 2.06-2.17 (1H, m), 2.22-2.26 (3H, s), 2.38-2.46 (1H, m), 2.63-2.74 (1H, m), 2.80- 2.91 (1H, m), 3.35-3.50 (2H, m), 5.70-5.85 (1H, m), 6.84-6.88 (2H, s), 7.37-7.50 (5H, m) A51 1H NMR (400 MHz, d4-methanol) δ (delta) 1.67-1.76 (1H, m), 2.02- 2.08 (6H, s), 2.15-2.26 (4H, m), 2.45-2.51 (1H, m), 2.52-2.56 (3H, s), 2.76-2.83 (1H, m), 2.90-2.97 (1H, m), 3.50-3.58 (2H, m), 6.84- 6.88 (2H, s) A52 1H NMR (400 MHz, d4-methanol) δ 1.68-1.79 (1H, m), 2.03- 2.06 (6H, s), 2.14-2.25 (4H, m), 2.47-2.54 (1H, m), 2.77-2.85 (1H, m), 2.91-2.99 (1H, m), 3.49- 3.56 (2H, t), 3.97-3.99 (3H, s), 6.84- 6.87 (2H, s), 7.00-7.02 (1H, s), 7.06- 7.11 (1H, t), 7.24-7.30 (1H, t), 7.39- 7.44 (1H, t), 7.57-7.61 (1H, d) A53 0 1H NMR (400 MHz, d4-methanol) δ (delta) 1.68-1.79 (1H, m), 2.02- 2.06 (6H, s), 2.13-2.25 (4H, m), 2.45-2.52 (1H, m), 2.76-2.83 (1H, m), 2.88-2.96 (1H, m), 3.52- 3.61 (2H, m), 6.83-6.87 (2H, s), 8.22-8.24 (1H, m), 8.97-8.98 (1H, m) A54 1H NMR (400 MHz, d4-methanol) δ (delta) 1.64-1.75 (1H, m), 2.02- 2.06 (6H, s), 2.10-2.21 (1H, m), 2.22-2.25 (3H, s), 2.44-2.50 (4H, m), 2.75-2.82 (1H, m), 2.88-2.96 (1H, m), 3.47-3.52 (2H, t), 4.10-4.12 (3H, s), 6.84-6.87 (2H, s) A55 1H NMR (400 MHz, d4-methanol) δ (delta) 1.69-1.81 (1H, m), 2.02- 2.06 (6H, s), 2.15-2.26 (4H, m), 2.46-2.53 (1H, m), 2.76-2.84 (1H, m), 2.89-2.98 (1H, m), 3.53- 3.67 (2H, m), 6.82-6.86 (2H, s), 8.64-8.67 (1H, m), 8.74-8.76 (1H, m), 9.21-9.23 (1H, m) A56 1H NMR (400 MHz, d4-methanol) δ (delta) 1.68-1.79 (1H, m), 2.01- 2.05 (6H, s), 2.14-2.26 (4H, m), 2.46-2.53 (1H, m), 2.61-2.64 (3H, s), 2.76-2.83 (1H, m), 2.89- 2.97 (1H, m), 3.52-3.66 (2H, m), 6.83-6.88 (2H, s), 8.56-8.58 (1H, s), 9.06-9.09 (1H, s). A57 1H NMR (400 MHz, d4-methanol) δ (delta) 1.69-1.80 (1H, m), 2.02- 2.05 (6H, s), 2.15-2.25 (4H, m), 2.46-2.52 (1H, m), 2.76-2.83 (1H, m), 2.89-2.97 (1H, m), 3.53- 3.66 (2H, m), 6.83-6.86 (2H, s), 8.19-8.24 (1H, d), 8.30-8.34 (1H, m), 8.93-8.95 (1H, m) A57A A58 1H NMR (400 MHz, d4-methanol) δ (delta) 1.67-1.78 (1H, m), 2.06- 2.09 (6H, s), 2.10-2.21 (1H, m), 2.26-2.29 (3H, s), 2.46-2.53 (1H, m), 2.78-2.85 (1H, m), 2.92- 3.00 (1H, m), 3.44-3.52 (2H, m), 3.90-3.92 (3H, s), 6.06-6.09 (1H, m), 6.76-6.79 (1H, m), 6.81-6.84 (1H, m), 6.88-6.91 (2H, s) A59 1H NMR (400 MHz, d4-methanol) δ (delta) 1.69-1.79 (1H, m), 2.00- 2.03 (6H, s), 2.16-2.25 (1H, m), 2.26-2.29 (3H, s), 2.47-2.54 (1H, m), 2.81-2.88 (1H, m), 2.92- 3.00 (1H, m), 3.52-3.58 (2H, t), 4.03-4.05 (3H, s), 6.87-6.91 (2H, s), 7.06-7.09 (1H, s), 7.26-7.29 (1H, s) A60 1H NMR (400 MHz, d4-methanol) δ (delta) 1.74-1.88 (1H, m), 2.04- 2.10 (6H, s), 2.22-2.32 (4H, m), 2.50-2.57 (1H, m), 2.82-2.90 (1H, m), 2.93-3.02 (1H, m), 3.59-3.72 (2H, m), 6.85-6.89 (2H, s), 9.44-9.47 (1H, s) A61 1H NMR (400 MHz, d4-methanol) δ (delta) 1.60-1.71 (1H, m), 1.98- 2.02 (6H, s), 2.08-2.18 (1H, m), 2.18-2.21 (3H, s), 2.37-2.48 (4H, m), 2.69-2.77 (1H, m), 2.84- 2.92 (1H, m), 3.41-3.54 (2H, m), 6.38-6.41 (1H, s), 6.80-6.83 (2H, s). A62 0 1H NMR (400 MHz, d4-methanol) δ (delta) 1.64-1.75 (1H, m), 1.99- 2.03 (6H, s), 2.11-2.21 (4H, m), 2.42-2.49 (1H, m), 2.53-2.56 (3H, s), 2.75-2.82 (1H, m), 2.85- 2.94 (1H, m), 3.48-3.54 (2H, t), 6.80-6.83 (2H, s), 7.36-7.41 (1H, m), 7.68-7.73 (1H, d), 8.35-8.39 (1H, d) A63 1H NMR (400 MHz, d4- methanol) δ 1.76-1.88 (1H, m), 2.05-2.11 (6H, s), 2.22-2.35 (4H, m), 2.52-2.60 (1H, m), 2.86-2.94 (1H, m), 2.96-3.03 (1H, m), 3.63-3.69 (2H, t), 6.84-6.88 (2H, s), 7.67-7.73 (1H, t), 7.75-7.81 (1H, t), 7.89-7.93 (1H, d), 7.93-7.97 (1H, d), 8.45-8.49 (1H, d), 8.93-8.98 (1H, d) A64 1H NMR (400 MHz, d4-methanol) δ (delta) 1.65-1.76 (1H, m), 1.98- 2.02 (6H, s), 2.10-2.21 (4H, m), 2.42- 2.49 (1H, m), 2.53-2.56 (3H, s), 2.72- 2.80 (1H, m), 2.85-2.93 (1H, m), 3.48-3.60 (2H, m), 7.36-7.40 (1H, d), 7.77-7.82 (1H, t), 7.84-7.88 (1H, d) A65 1H NMR (400 MHz, d4-methanol) δ (delta) 1.64-1.76 (1H, m), 2.02- 2.07 (6H, s), 2.13-2.25 (4H, m), 2.38-2.46 (1H, m), 2.69-2.77 (1H, m), 2.82-2.90 (1H, m), 3.48- 3.62 (2H, m), 3.91-3.96 (3H, s), 6.81-6.85 (2H, s), 7.12-7.15 (1H, s), 7.57-7.60 (1H, s) A66 1H NMR (400 MHz, d4-methanol) δ (delta) 1.70-1.81 (1H, m), 2.06- 2.11 (6H, s), 2.14-2.28 (4H, m), 2.36-2.44 (1H, m), 2.70-2.77 (1H, m), 2.80-2.89 (1H, m), 3.54- 3.60 (2H, t), 6.68-6.73 (1H, d), 6.84-6.88 (2H, s), 7.30-7.34 (1H, d), 7.53-7.59 (1H, t) A69 1H NMR (400 MHz, d4methanol) δ (delta) 1.64-1.75 (1H, m), 2.00- 2.07 (6H, d), 2.08-2.19 (4H, m), 2.20-2.27 (1H, m), 2.53-2.61 (1H, m), 2.63-2.71 (1H, m), 3.47- 3.61 (2H, m), 3.94-4.00 (6H, s), 6.18-6.21 (1H, s), 6.73-6.78 (2H, d) A70 1H NMR (400 MHz, d4-methanol) δ (delta) 1.61-1.72 (1H, m), 1.97- 2.01 (6H, s), 2.07-2.20 (4H, m), 2.29-2.34 (3H, s), 2.40-2.47 (1H, m), 2.71-2.78 (1H, m), 2.83- 2.91 (1H, m), 3.44-3.50 (2H, t), 6.78-6.81 (2H, s), 7.67-7.69 (1H, s) A71 1H NMR (400 MHz, d4-methanol) δ (delta) 1.67-1.78 (1H, m), 2.05- 2.09 (6H, s), 2.12-2.24 (1H, m), 2.26- 2.29 (3H, s), 2.47-2.54 (1H, m), 2.55- 2.58 (3H, s), 2.76-2.84 (1H, m), 2.91- 2.99 (1H, m), 3.49-3.58 (2H, m), 6.87-6.91 (2H, s) A72 1H NMR (400 MHz, d4-methanol) δ (delta) 1.60-1.71 (1H, m), 1.98- 2.02 (6H, d), 2.03-2.15 (1H, m), 2.15-2.18 (3H, s), 2.18-2.21 (3H, s), 2.39-2.46 (1H, m), 2.69-2.77 (1H, m), 2.85-2.93 (1H, m), 3.39-3.45 (2H, t), 3.97-3.99 (3H, s), 6.47-6.50 (1H, s), 6.79-6.83 (2H, s) A73 1H NMR (400 MHz, d4-methanol) δ (delta) 1.62-1.73 (1H, m), 1.98- 2.02 (6H, s), 2.08-2.18 (1H, m), 2.18-2.21 (3H, s), 2.40-2.47 (1H, m), 2.64-2.67 (3H, s), 2.71- 2.78 (1H, m), 2.84-2.92 (1H, m), 3.46-3.53 (2H, m), 6.79-6.82 (2H, s), 7.95-7.97 (1H, s) A74 0 1H NMR (400 MHz, d4 methanol) δ 1.64-1.75 (1H, m), 1.98-2.01 (6H, s), 2.12-2.22 (4H, m), 2.42-2.49 (1H, m), 2.75-2.83 (1H, m), 2.85-2.93 (1H, m), 3.52-3.58 (2H, t), 6.76-6.79 (2H, s), 7.16-7.21 (1H, t), 7.31-7.37 (1H, t), 7.47-7.52 (1H, d), 8.16-8.21 (1H, d) A75 1H NMR (400 MHz, d4 methanol) δ (delta) 1.59-1.70 (1H, m), 1.98- 2.02 (6H, s), 2.03-2.17 (1H, m), 2.17-2.21 (3H, s), 2.21-2.24 (3H, s), 2.38-2.45 (1H, m), 2.69- 2.77 (1H, m), 2.83-2.91 (1H, m), 3.42-3.48 (2H, t), 3.72-3.75 (3H, s), 6.42-6.44 (1H, s), 6.79-6.82 (2H, s) A76 1H NMR (400 MHz, d4-methanol) δ 1.75-1.86 (1H, m), 2.07-2.10 (6H, s), 2.20-2.30 (4H, m), 2.41-2.46 (1H, m), 2.64-2.67 (3H, s), 2.75-2.83 (1H, m), 2.85-2.93 (1H, m), 3.59-3.63 (2H, t), 6.81-6.85 (2H, s), 7.01-7.07 (1H, t), 7.42-7.48 (1H, t), 7.51-7.56 (1H, d), 9.02-9.07 (1H, d) A77 1H NMR (400 MHz, d4-methanol) δ (delta) 1.60-1.71 (1H, m), 1.99- 2.02 (6H, s), 2.07-2.17 (1H, m), 2.17-2.20 (3H, s), 2.40-2.47 (1H, m), 2.70-2.78 (1H, m), 2.84- 2.92 (1H, m), 3.43-3.49 (2H, t), 3.86-3.88 (3H, s), 6.79-6.82 (2H, s), 7.99-8.02 (1H, s) A78 1H NMR (400 MHz, d4-methanol) δ (delta) 1.63-1.74 (1H, m), 1.98- 2.02 (6H, s), 2.11-2.22 (4H, m), 2.43-2.50 (1H, m), 2.61-2.64 (3H, s), 2.76-2.83 (1H, m), 2.87- 2.95 (1H, m), 3.43-3.59 (2H, m), 6.80-6.84 (2H, s), 8.84-8.86 (1H, s) A79 1H NMR (400 MHz, d4-methanol) δ (delta) 1.61-1.72 (1H, m), 1.98- 2.02 (6H, s), 2.05-2.15 (1H, m), 2.19-2.22 (3H, s), 2.40-2.47 (1H, m), 2.52-2.55 (3H, s), 2.62- 2.64 (3H, s), 2.69-2.77 (1H, m), 2.85-2.93 (1H, m), 3.41-3.46 (2H, t), 6.80-6.83 (2H, s) A83 1H NMR (400 MHz, d4-methanol) δ (delta) 8.63 (d, 1H), 8.09 (d, 1H), 7.97-7.93 (m, 1H), 7.56-7.52 (m, 1H), 7.22 (s, 2H), 3.66-3.55 (m, 2H), 2.97- 2.93 (m, 1H), 2.81 (br, 1H), 2.51 (d, 1H), 2.39 (q, 2H), 2.26-2.14 (m, 1H), 2.06 (2, 3H), 1.81-1.68 (m, 1H), 1.07- 1.03 (m, 3H). A84 (As a mixture of atropisomers) 1H NMR (400 MHz, CDCl.sub.3) δ (delta) 1.12 (dt, 3H), 1.78-1.94 (m, 2H), 2.04 (s, 3H), 2.11 (s, 1.5H), 2.15 (s, 1.5H), 2.18 (d, 1H), 2.44 (dt, 2H), 2.81-3.04 (m, 2H), 3.35-3.53 (m, 1H), 4.04-4.25 (m, 1H), 7.05-7.19 (m, 2H), 7.46-7.60 (m, 1H), 7.91 (t, 1H), 8.22 (d, 1H), 8.61 (d, 1H), 8.69 (br. s., 1H), 12.25 (br. s., 1H). A85 1H NMR (400 MHz, CDCl.sub.3) δ (delta) 1.05-1.18 (m, 3H), 1.87 (t, 1H), 2.10- 2.23 (m, 4H), 2.40-2.56 (m, 2H), 2.83- 3.00 (m, 2H), 3.01 (s, 1H), 3.43 (d, 1H), 4.08-4.21 (m, 1H), 7.20-7.26 (m, 2H), 7.42-7.50 (m, 1H), 7.92 (t, 1H), 8.22 (d, 1H), 8.61 (d, 1H), 8.71 (br. s., 1H). A86 (As a mixture of atropisomers) 1H NMR (400 MHz, CDCl.sub.3) δ (delta) 12.35 (br, 1H), 8.71 (br, 1H), 8.62 (d, 1H), 8.23 (d, 1H), 7.96-7.88 (m, 1H), 7.57-7.49 (m, 3H), 7.26 (s, 2H), 7.10 (t, 2H), 4.18 (d, 1H), 3.44 (d, 1H), 3.04-2.96 (m, 1H), 2.96-2.88 (m, 1H), 2.58-2.54 (m, 2H), 2.26 (s, 1.5H), 2.22 (s, 1.5H), 2.26-2.17 (m, 2H), 1.89 (t, 1H), 1.20-1.16 (m, 3H) A87 00 1H NMR (400 MHz, CDCl.sub.3) δ (delta) 8.71 (br, 1H), 8.61 (d, 1H), 8.22 (d, 1H), 8.01-7.84 (m, 2H), 7.62 (s, 1H), 7.57-7.49 (m, 1H), 7.46-7.32 (m, 2H), 4.25-4.11 (m, 1H), 3.46 (br, 1H), 3.05-2.83 (m, 2H), 2.56-2.52 (m, 2H), 2.25-2.20 (m, 5H), 1.88 (br, 1H), 1.23- 1.11 (m, 3H) A88 01 (As a mixture of diastereoisomers) 1H NMR (400 MHz, d4-methanol) δ (delta) 0.96-1.03 (3H, m), 1.14- 1.20 (1H, t), 1.55-1.82 (3H, m), 2.00- 2.03 (3H, s), 2.03-2.06 (3H, s), 2.12- 2.21 (1H, m), 2.22-2.25 (3H, s), 2.46- 2.55 (1H, m), 2.82-2.92 (1H, m), 3.56- 3.63 (1H, q), 4.13-4.23 (1H, m), 6.83- 6.87 (2H, d), 7.43-7.49 (2H, m), 7.50- 7.56 (1H, m), 7.83-7.88 (2H, m) A89 02 1H NMR (400 MHz, d4-methanol) δ (delta) 1.70-1.81 (1H, m), 2.05- 2.09 (6H, s), 2.17-2.28 (4H, m), 2.48- 2.55 (1H, m), 2.78-2.86 (1H, m), 2.91- 3.00 (1H, m), 3.53-3.68 (2H, m), 6.86- 6.90 (2H, s), 7.24-7.29 (1H, m), 8.01- 8.05 (1H, m), 8.08-8.16 (1H, m) A89A 03 A91 04 1H NMR (400 MHz, d4-methanol) δ (delta) 1.70-1.81 (1H, m), 1.97- 2.02 (6H, d), 2.08-2.18 (1H, m), 2.18-2.22 (3H, s), 2.42-2.49 (1H, m), 2.72-2.80 (1H, m), 2.86- 2.94 (1H, m), 3.49-3.63 (2H, m), 3.91-3.94 (3H, s), 6.79-6.83 (2H, d), 6.88-6.92 (1H, d), 7.61-7.65 (1H, d), 7.72-7.78 (1H, t). A92 05 1H NMR (400 MHz, d4-methanol) δ (delta) 1.35-1.42 (3H, t), 1.78- 1.89 (1H, m), 2.04-2.09 (6H, d), 2.13-2.24 (1H, m), 2.25-2.29 (3H, s), 2.49-2.56 (1H, m), 2.79- 2.87 (1H, m), 2.93-3.01 (1H, m), 3.56-3.69 (2H, m), 4.39-4.50 (2H, m), 6.86-6.90 (2H, d), 6.92-6.97 (1H, d), 7.66-7.71 (1H, d), 7.78-7.85 (1H, t). A93 06 1H NMR (400 MHz, d4-methanol) δ (delta) 1.75-1.86 (1H, m), 2.01- 2.06 (6H, s), 2.13-2.25 (4H, m), 2.47-2.54 (1H, m), 2.77-2.86 (1H, m), 2.90-2.98 (1H, m), 3.57- 3.70 (2H, m), 6.80-6.86 (2H, d), 7.38-7.51 (3H, m), 7.94-8.18 (5H, m) A94 07 1H NMR (400 MHz, d4-methanol) δ (delta) 1.69-1.80 (1H, m), 2.01- 2.06 (6H, s), 2.16-2.26 (4H, m), 2.46-2.53 (1H, m), 2.75-2.83 (1H, m), 2.89-2.97 (1H, m), 3.53- 3.69 (2H, m), 6.82-6.86 (2H, s), 7.94-7.99 (1H, d), 8.18-8.24 (1H, t), 8.32-8.36 (1H, d) A96 08 1H NMR (400 MHz, d4-methanol) δ (delta) 1.70-1.82 (1H, m), 2.05- 2.09 (6H, s), 2.17-2.28 (4H, m), 2.49-2.56 (1H, m), 2.80-2.88 (1H, m), 2.92-3.01 (1H, m), 3.53- 3.68 (2H, m), 6.86-6.90 (2H, s), 7.59-7.65 (1H, m), 7.70-7.78 (1H, t), 8.45-8.50 (1H, d) A97 09 1H NMR (400 MHz, d4-methanol) δ (delta) 1.71-1.82 (1H, m), 2.05- 2.08 (6H, s), 2.16-2.28 (4H, m), 2.47-2.55 (1H, m), 2.78-2.86 (1H, m), 2.91-2.99 (1H, m), 3.56- 3.65 (2H, s), 7.71-7.79 (1H, m), 8.15-8.21 (1H, m), 8.52-8.55 (1H, d) A98 0 1H NMR (400 MHz, d4-methanol) δ (delta) 1.73-1.84 (1H, m), 2.12- 2.27 (7H, m), 2.51-2.58 (1H, m), 2.81-2.89 (1H, m), 2.94-3.02 (1H, m), 3.57-3.67 (2H, m), 7.42- 7.45 (2H, s), 7.55-7.61 (1H, t), 7.64-7.66 (1H, s), 7.97-8.03 (1H, t), 8.10-8.15 (1H, d), 8.31-8.34 (1H, s), 8.63-8.67 (1H, d) A99 1H NMR (400 MHz, d4-methanol) δ (delta) 1.73-1.84 (1H, m), 2.12- 2.27 (7H, m), 2.51-2.58 (1H, m), 2.81-2.89 (1H, m), 2.94-3.02 (1H, m), 3.57-3.67 (2H, m), 7.42- 7.45 (2H, s), 7.55-7.61 (1H, t), 7.64-7.66 (1H, s), 7.97-8.03 (1H, t), 8.10-8.15 (1H, d), 8.31-8.34 (1H, s), 8.63-8.67 (1H, d) A100 1H NMR (400 MHz, CDCl.sub.3) δ (delta) 8.71 (br, 1H), 8.61 (d, 1H), 8.22 (d, 1H), 8.01-7.84 (m, 2H), 7.62 (s, 1H), 7.57-7.49 (m, 1H), 7.46-7.32 (m, 2H), 4.25-4.11 (m, 1H), 3.46 (br, 1H), 3.05- 2.83 (m, 2H), 2.56-2.52 (m, 2H), 2.25- 2.20 (m, 5H), 1.88 (br, 1H), 1.23- 1.11 (m, 3H) A101 1H NMR (400 MHz, CDCl.sub.3) δ (delta) 8.71 (br, 1H), 8.61 (d, 1H), 8.22 (d, 1H), 8.01-7.84 (m, 2H), 7.62 (s, 1H), 7.57-7.49 (m, 1H), 7.46-7.32 (m, 2H), 4.25-4.11 (m, 1H), 3.46 (br, 1H), 3.05- 2.83 (m, 2H), 2.56-2.52 (m, 2H), 2.25- 2.20 (m, 5H), 1.88 (br, 1H),1.23- 1.11 (m, 3H)

(182) The following compound is also one embodiment of the present invention:

(183) ##STR00214##

(184) Additional compounds in Table A2 below illustrate the present invention, and are particular embodiments of the compounds of formula (I) according to the present invention. For the most part (in particular for the R.sup.1═R.sup.3=methyl compounds, e.g. compounds A102, A103 and A104), these compounds are thought to be preparable, for example by methods similar to those shown in the Examples and/or in the process section hereinabove using appropriate starting materials and with any appropriate and/or necessary process changes.

(185) TABLE-US-00012 TABLE A2 Compound number Structure Data A102 1H NMR (400 MHz, CDCl.sub.3) δ (delta) 1.99 (s, 3H), 2.08-2.42 (m, 7H), 2.91 (br. s., 1H), 3.50 (br. s., 1H), 3.89 (br. s., 1H), 7.39- 7.51 (m, 2H), 7.57 (br. s., 2H), 7.85 (t, 1H), 8.14 (d, 1H), 8.42 (s, 1H), 8.55 (d, 2H) A103 A104 1H NMR (400 MHz, CDCl.sub.3) δ (delta) 1.84-1.95 (m, 1H), 2.15-2.25 (m, 5H), 2.28 (s, 3H), 2.85-2.96 (m, 1H), 2.96-3.06 (m, 1H), 3.37- 3.48 (m, 1H), 4.15-4.26 (m, 1H), 7.24-7.28 (m, 2H), 7.37 (d, 2H), 7.46-7.56 (m, 3H), 7.92 (td, 1H), 8.23 (d, 1H), 8.62 (d, 1H), 8.71 (br. s., 1H). A105 1H NMR (500 MHz, D.sub.2O) δ (delta) 1.79-1.95 (m, 1H), 2.34 (s, 5H), 2.86-2.96 (m, 1H), 2.98-3.15 (m, 1H), 3.56- 3.77 (m, 2H), 7.23-7.28 (m, 1H), 7.24 (s, 2H), 8.12- 8.30 (m, 1H), 8.56-8.67 (m, 1H), 8.70-8.81 (m, 1H), 8.86- 9.07 (m, 1H) A106 1H NMR (400 MHz, d4- methanol) δ (delta) 1.82 (br. s., 1H), 2.14-2.35 (m, 1H), 2.50- 2.70 (m, 1H), 2.84-3.21 (m, 2H), 3.25-3.42 (m, 1H), 3.53- 3.76 (m, 1H), 7.20 (s, 2H), 7.54-7.73 (m, 3H), 7.54- 7.73 (m, 2H), 7.85-8.01 (m, 1H), 8.31-8.47 (m, 1H), 8.66- 9.01 (m, 1H) A107 0 A108

(186) Additional compounds in Table A3 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 and with any appropriate and/or necessary process changes.

(187) It should be noted that certain compounds of the invention exist as a mixture of isomers, including atropisomers, 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 were recorded at ambient temperature.

(188) TABLE-US-00013 TABLE A3 Compound number Structure Data A109 .sup.1H NMR (400 MHz, CDCl.sub.3) δ (delta) 2.00 (s, 2H), 2.04-2.15 (m, 1H), 2.16-2.36 (m, 6H), 2.91 (m, 2H), 3.48 (d, 1H), 4.00 (br. s., 1H), 6.65-6.80 (m, 1H), 7.06 (d, 2H), 7.22 (s, 2H), 7.49 (m, 1H), 7.74-8.01 (m, 1H), 8.16 (d, 1H), 8.58 (d, 1H), 8.63 (br. s., 1H) A110 .sup.1H NMR (400 MHz, CDCl.sub.3) δ (delta) 1.83-1.99 (m, 1H), 2.10- 2.39 (m, 8H), 2.77-3.14 (m, 2H), 3.32-3.58 (m, 1H), 3.82-4.47 (m, 1H), 7.15 (t, 1H), 7.20 (s, 2H), 7.35-7.43 (m, 1H), 7.49 (br. s., 1H), 7.53-7.64 (m, 1H), 7.76-7.99 (m, 1H), 8.17 (br. s., 1H), 8.49- 8.64 (m, 1H), 8.64-8.84 (m, 1H) A111 1H NMR (400 MHz, CDCl.sub.3) δ (delta) 1.98 (br. s., 1H), 2.10 (br. s., 1H), 2.21 (s, 3H), 2.24 (s, 3H), 2.26-2.34 (m, 1H), 2.81-3.03 (m, 2H), 3.37-3.57 (m, 1H), 4.01 (br. s., 1H), 7.24 (s, 2H), 7.28 (s, 1H), 7.29-7.36 (m, 1H), 7.43 (d, 1H), 7.49 (dd, 1H), 7.53 (s, 1H), 7.88 (t, 1H), 8.17 (d, 1H), 8.58 (d, 1H), 8.62 (br. s., 1H) A112 1H NMR (400 MHz, CDCl.sub.3) δ (delta) 1.79-2.50 (m, 13H), 2.88 (d, 2H), 3.29-3.53 (m, 1H), 6.89 (s, 2H), 7.05-7.22 (m, 1H), 7.81- 8.19 (m, 2H), 8.19-8.39 (m, 1H) A113 1H NMR (400 MHz, CDCl.sub.3) δ (delta) 1.79-2.50 (m, 13H), 2.88 (d, 2H), 3.29-3.53 (m, 1H), 6.89 (s, 2H), 7.05-7.22 (m, 1H), 7.81- 8.19 (m, 2H), 8.19-8.39 (m, 1H) A114 1H NMR (400 MHz, CDCl.sub.3) δ (delta) 1.80-2.16 (m, 11H), 2.16- 2.33 (m, 1H), 2.71-2.93 (m, 2H), 3.38-3.57 (m, 1H), 3.64-3.90 (m, 1H), 6.95-7.22 (m, 3H), 7.86-8.11 (m, 2H), 8.21 (br. s., 1H) A115 1H NMR (400 MHz, CDCl.sub.3) δ (delta) 1.27 (d, 9H), 1.91-2.22 (m, 11H), 2.86 (s, 2H), 3.09-3.23 (m, 1H), 3.85-4.06 (m, 1H), 6.18-6.37 (m, 1H), 7.09 (br. s., 1H), 7.16- 7.24 (m, 1H) A116 1H NMR (400 MHz, CDCl.sub.3) δ (delta) 1.76-2.12 (m, 11H), 2.13- 2.37 (m, 1H), 2.66-2.98 (m, 2H), 3.16-3.41 (m, 1H), 3.70 (d, 1H), 6.91-7.17 (m, 4H), 7.75 (ddd, 2H), 7.86 (br. s., 1H) A117 0 1H NMR (400 MHz, CDCl.sub.3) δ (delta) 1.90-2.09 (m, 2H), 2.12- 2.36 (m, 7H), 2.73-3.05 (m, 2H), 3.36-3.61 (m, 1H), 3.66-4.17 (m, 1H), 7.36-7.49 (m, 2H), 7.53 (br. s., 2H), 7.63 (dd, 1H), 7.85 (t, 1H), 8.15 (d, 1H), 8.45 (br. s., 1H), 8.48-8.67 (m, 2H) A118 1H NMR (400 MHz, CDCl.sub.3) δ (delta) 1.61-3.03 (m, 13H), 3.20- 3.77 (m, 2H), 3.77-4.06 (m, 1H), 6.83 (s, 2H), 7.65-8.63 (m, 4H) A119 1H NMR (400 MHz, CDCl.sub.3) δ (delta) 1.65-3.11 (m, 17H), 3.24- 3.69 (m, 1H), 3.88-4.30 (m, 1H), 6.86 (s, 2H), 7.26 (s, 1H), 7.89- 8.20 (m, 1H), 8.42 (d, 1H), 8.48- 8.79 (m, 1H) A120 1H NMR (400 MHz, CDCl.sub.3) δ (delta) 1.83-2.4 (m, 11H), 2.74- 3.11 (m, 2H), 3.45-3.52 (m, 2H), 3.97 (br. s., 1H), 6.84 (br. s., 2H), 7.9-8.09 (m, 2H), 8.48-8.7 (m, 2H) A120A 1H NMR (400 MHz, CDCl.sub.3) δ (delta) 1.83-2.4 (m, 11H), 2.74- 3.11 (m, 2H), 3.45-3.52 (m, 2H), 3.97 (br. s., 1H), 6.84 (br. s., 2H), 7.9-8.09 (m, 2H), 8.48-8.7 (m, 2H) A120B 1H NMR (400 MHz, CDCl.sub.3) δ (delta) 1.83-2.4 (m, 11H), 2.74- 3.11 (m, 2H), 3.45-3.52 (m, 2H), 3.97 (br. s., 1H), 6.84 (br. s., 2H), 7.9-8.09 (m, 2H), 8.48-8.7 (m, 2H) A121 1H NMR (400 MHz, CDCl.sub.3) δ (delta) 1.48-2.30 (m, 11H), 2.75- 3.08 (m, 2H), 3.29-3.69 (m, 2H), 3.97 (br. s., 1H), 6.84 (br. s., 2H), 7.33-7.81 (m, 1H), 7.90-8.71 (m, 3H) A122 1H NMR (400 MHz, CDCl.sub.3) δ (delta) 1.87-2.05 (m, 2H), 2.10 (s, 3H), 2.12 (s, 3H), 2.18-2.33 (m, 1H), 2.74-2.97 (m, 2H), 3.39-3.57 (m, 1H), 3.73 (s, 3H), 3.91 (br. s., 1H), 6.59 (s, 2H), 7.36-7.57 (m, 1H), 7.87 (t, 1H), 8.14 (d, 1H), 8.40-8.72 (m, 2H) A123 1H NMR (400 MHz, d6-DMSO) δ (delta) 1.51-1.64 (m, 1H), 2.01 (s, 3H), 2.02 (s, 3H), 2.04-2.14 (m, 1H), 2.38 (dd, 1H), 2.57-2.71 (m, 1H), 2.78-2.93 (m, 1H), 3.35-3.50 (m, 2H), 6.96-7.03 (m, 2H), 7.03- 7.12 (m, 1H), 7.61 (ddd, 1H), 7.94-8.11 (m, 2H), 8.65 (d, 1H), 8.94 (t, 1H) A124 1H NMR (400 MHz, CDCl.sub.3) δ (delta) 1.81-1.90 (m, 1H), 2.08 (d, 1H), 2.14 (s, 3H), 2.18 (s, 3H), 2.19-2.25 (m, 1H), 2.84-2.92 (m, 1H), 2.92-3.00 (m, 1H), 3.37- 3.47 (m, 1H), 4.13-4.23 (m, 1H), 7.07 (s, 2H), 7.48-7.58 (m, 1H), 7.92 (td, 1H), 8.22 (d, 1H), 8.61 (d, 1H), 8.71 (br. s., 1H), 12.52 (br. s., 1H) A125 0 1H NMR (400 MHz, CDCl.sub.3) δ (delta) 1.85 (t, 1H), 2.09-2.12 (m, 1H), 2.14 (s, 3H), 2.18 (s, 3H), 2.20-2.29 (m, 1H), 2.82- 3.04 (m, 2H), 3.42 (d, 1H), 4.14- 4.25 (m, 1H), 7.22 (s, 2H), 7.54 (d, 1H), 7.92 (t, 1H), 8.22 (d, 1H), 8.61 (d, 1H), 8.71 (br. s., 1H), 12.53 (br. s., 1H) A126 1H NMR (400 MHz, CDCl.sub.3) δ (delta) 1.83-2.02 (m, 1H), 2.02- 2.19 (m, 7H), 2.26 (d, 1H), 2.82- 3.00 (m, 2H), 3.35-3.57 (m, 1H), 3.81-4.16 (m, 1H), 4.29 (q, 2H), 6.64 (s, 2H), 7.50 (dd, 5.20 1H), 7.89 (td, 1H), 8.16 (d, 1H), 8.59 (d, 1H), 8.64 (br. s., 1H) A126A 1H NMR (400 MHz, CDCl.sub.3) δ (delta) 1.84-1.97 (m, 1H), 2.09- 2.28 (m, 8H), 2.84-2.93 (m, 1H), 2.97 (d, 1H), 3.44 (d, 1H), 4.05- 4.23 (m, 1H), 6.85 (s, 2H), 7.46- 7.58 (m, 2H), 7.87-7.96 (m, 2H), 8.22 (d, 1H), 8.61 (d, 1H), 8.64- 8.72 (m, 1H) A126B 1H NMR (400 MHz, CDCl.sub.3) δ (delta) 1.91 (t, 1H), 2.10-2.29 (m, 8H), 2.89 (dd, 6.72 1H), 2.98 (br. s., 1H), 3.45 (d, 1H), 4.13 (d, 1H), 6.87 (s, 2H), 7.52 (br. s., 1H), 7.87-7.99 (m, 2H), 8.22 (d, 1H), 8.27 (br. s., 1H), 8.60 (br. s., 1H), 8.69 (br. s., 1H) A127 1H NMR (400 MHz, CDCl.sub.3) δ (delta) 1.77-2.43 (m, 12H), 2.67- 3.17 (m, 2H), 3.26-3.87 (m, 2H), 6.89 (s, 2H), 7.45-7.57 (m, 1H), 8.07-8.68 (m, 3H) A128 1H NMR (500 MHz, CDCl.sub.3) δ (delta) 1.77-2.43 (m, 12H), 2.67- 3.17 (m, 2H), 3.26-3.87 (m, 2H), 6.89 (s, 2H), 7.45-7.57 (m, 1H), 8.07-8.68 (m, 3H) A129 1H NMR (500 MHz, CDCl.sub.3) δ (delta) 1.67-2.47 (m, 9H), 2.67- 3.09 (m, 2H), 3.37-3.62 (m, 1H), 3.79-4.08 (m, 1H), 7.27 (d, 2H), 7.45-7.66 (m, 2H), 7.84 (s, 1H), 8.19 (br. s., 1H), 8.28-8.64 (m, 1.5H), 11.5-13 (br. s., 0.5H). A130 1H NMR (500 MHz, CDCl.sub.3) δ (delta) 1.76-1.99 (m, 1H), 2.08- 2.43 (m, 8H), 2.60 (s, 3H), 2.75- 3.10 (m, 2H), 3.47 (d, 1H), 4.12 (q, 1H), 7.28-7.42 (m, 3H), 7.60 (s, 1H), 7.67-8.06 (m, 3H), 8.71 (br. s., 1H) A131 1H NMR (500 MHz, CDCl.sub.3) δ (delta) 1.76-1.95 (m, 1H), 1.95- 2.18 (m, 7H), 2.18-2.43 (m, 1H), 2.65-2.99 (m, 2H), 3.36-3.55 (m, 1H), 3.54-3.83 (m, 1H), 7.18 (s, 2H), 7.36 (d, 1H), 7.54 (s, 1H), 7.65-7.86 (m, 2H), 7.96-8.33 (m, 1H) A132 1H NMR (500 MHz, CDCl.sub.3) δ (delta) 1.55-2.47 (m, 9H), 2.61- 3.06 (m, 2H), 3.27-3.60 (m, 1H), 3.60-4.06 (m, 1H), 7.23 (s, 2H), 7.40-8.13 (m, 5H), 8.14-8.65 (m, 1H) A133 0 1H NMR (500 MHz, CDCl.sub.3) δ (delta) 1.77-2.22 (m, 8H), 2.22- 2.48 (m, 1H), 2.92 (m, 2H), 3.40- 3.59 (m, 1H), 3.58-4.00 (m, 1H), 7.20 (d, 2H), 7.31-7.63 (m, 3H), 7.81 (s, 1H), 8.15-8.53 (m, 2H) A134 1H NMR (500 MHz, CDCl.sub.3) δ (delta) 1.82-2.42 (m, 9H), 2.87 (m, 2H), 3.32-3.59 (m, 1H), 3.69- 4.05 (m, 1H), 7.25-7.4 (s, 2H), 7.54-7.94 (m, 4H), 8.10 (d, 1H), 8.20-8.54 (m, 1H) A135 1H NMR (500 MHz, CDCl.sub.3) δ (delta) 1.87-2.02 (m, 2H), 2.07- 2.47 (m, 7H), 2.69-3.05 (m, 2H), 3.48 (d, 1H), 3.64-4.01 (m, 1H), 6.84-7.37 (m, 3H), 7.57 (s, 1H), 7.72-8.45 (m, 4H) A136 1H NMR (500 MHz, CDCl.sub.3) δ (delta) 1.52-2.57 (m, 8H), 2.57- 3.19 (m, 2H), 3.19-3.80 (m, 2H), 3.80-4.22 (m, 1H), 6.97-7.46 (m, 1H), 7.57 (s, 1H), 7.83 (s, 1H), 7.88-8.35 (m, 2H), 8.35-8.85 (m, 2H), 11.84-12.62 (m, 1H) A137 1H NMR (500 MHz, CDCl.sub.3) δ (delta) 1.56-2.7 (m, 8H), 2.7-3.02 (br. s., 2H), 3.54 (br. s., 2H), 3.74- 4.06 (m, 1H), 7.03-7.33 (m, 2H), 7.56 (s, 1H), 7.81 (s, 1H), 7.97- 9.02 (m, 3.5H), 11.89 (br. s., 0.5H) A138 1H NMR (500 MHz, CDCl.sub.3) δ (delta) 1.58-2.57 (m, 9H), 2.89 (dd, 2H), 3.25-4.30 (m, 2H), 7.2- 7.3 (s, 2H), 7.40-7.70 (m, 2H), 7.74-7.97 (m, 1H), 8.16 (br. s., 1H), 8.36-8.73 (m, 1.5H), 11.52- 12.52 (m, 0.5H) A139 1H NMR (500 MHz, CDCl.sub.3) δ (delta) 1.51-2.58 (m, 9H), 2.62- 3.20 (m, 2H), 3.28-3.82 (m, 1H), 3.84-4.29 (m, 1H), 7.2-7.3 (m, 2H), 7.47-7.67 (m, 1H), 7.68-7.96 (m, 2H), 8.10 (br. s., 1H), 8.38 (br. s., 1H), 8.55 (br. s., 0.5H), 11.49- 12.53 (m, 0.5H) A140 1H NMR (500 MHz, CDCl.sub.3) δ (delta) 1.72-2.52 (m, 9H), 2.60- 3.10 (m, 2H), 3.47 (m, 1H), 3.62- 3.90 (m, 1H), 6.99-7.38 (m, 3H), 7.55 (s, 1H), 7.81 (s, 1H), 7.89- 8.04 (m, 1H), 8.08-8.32 (m, 1H) A141 1H NMR (400 MHz, CDCl.sub.3) δ (delta) 1.68-2.50 (m, 9H), 2.73- 3.10 (m, 2H), 3.38-3.62 (m, 1H), 3.86-4.27 (m, 1H), 7.12-7.42 (m, 2H), 7.45-7.60 (s, 2H), 7.85 (s, 1H), 8.00-8.19 (m, 1H), 8.21-8.54 (m, 0.5H), 11.5-13.5 (m, 0.5H). A141A 1H NMR (500 MHz, CDCl.sub.3) δ (delta) 1.93-2.07 (m, 2H), 2.11 (s, 3H), 2.13 (s, 3H), 2.18-2.33 (m, 1H), 2.50 (t, 1H), 2.75-3.03 (m, 2H), 3.37-3.59 (m, 1H), 3.92 (br. s., 1H), 4.62 (s, 2H), 6.66 (s, 2H), 7.37-7.59 (m, 1H), 7.87 (t, 1H), 8.15 (d, 1H), 8.57 (d, 2H) A142 0 1H NMR (500 MHz, d4-methanol) δ (delta) 1.79 (ddt, 1H), 2.18 (s, 6H), 2.20-2.27 (m, 1H), 2.55 (dd, 1H), 2.81-2.90 (m, 1H), 2.99 (dd, 1H), 3.54-3.68 (m, 2H), 7.48 (s, 2H), 7.54 (d, 1H), 7.95 (t, 1H), 8.07 (s, 1H), 8.10 (d, 1H), 8.62 (br. s., 1H), 8.84 (s, 1H). A143 1H NMR (400 MHz, d4-methanol) δ (delta) 6.76 (2H, s), 3.39 (2H, t), 2.86-2.78 (1H, m), 2.72-2.62 (1H, m), 2.65 (3H, s), 2.37 (1H, d) 2.14 (3H, s), 2.10-2.02 (1H, m), 1.94 (6H, s), 1.64-1.55 (1H, m) A144 1H NMR (500 MHz, D.sub.2O) δ (delta) 1.70-1.85 (m, 1H), 2.08- 2.21 (m, 1H), 2.29 (s, 4H), 2.65- 2.82 (m, 2H), 3.45-3.61 (m, 2H), 7.14-7.39 (m, 3H), 7.82-7.96 (m, 1H), 8.01-8.25 (m, 1H) A145 1H NMR (500 MHz, d4-methanol) δ (delta) 6.74 (2H, s), 3.72 (3H, s), 3.45-3.33 (2H, m), 2.87-2.78 (1H, m), 2.72-2.65 (1H, m), 2.38 (1H, m), 2.18 (3H, s), 2.14 (3H, s), 2.09-2.02 (1H, m), 1.94 (6H, s), 1.65-1.54 (1H, m) A146 1H NMR (500 MHz, CDCl.sub.3) δ (delta) 2.00-2.35 (m, 12H), 2.90 (s, 2H), 3.38-3.53 (m, 1H), 4.12 (d, 1H), 6.89 (s, 2H), 7.41-7.63 (m, 1H), 8.04-8.20 (m, 1H), 8.25- 8.43 (m, 1H) A147 1H NMR (500 MHz, CDCl.sub.3) δ (delta) 1.85-2.16 (m, 8H), 2.23 (s, 4H), 2.85 (d, 2H), 3.36-3.68 (m, 1H), 3.68-3.99 (m, 1H), 6.84 (s, 2H), 8.05 (s, 4H) A148 1H NMR (500 MHz, CDCl.sub.3) δ (delta) 1.82-2.16 (m, 8H), 2.22 (s, 4H), 2.64-2.95 (m, 2H), 3.42-3.67 (m, 1H), 3.68-3.96 (m, 1H), 6.73- 6.96 (m, 2H), 7.60-7.76 (m, 1H), 8.25-8.51 (m, 2H), 8.69-8.83 (m, 1H) A149 1H NMR (500 MHz, CDCl.sub.3) δ (delta) 1.75-1.95 (m, 1H), 1.95- 2.13 (m, 7H), 2.22 (s, 4H), 2.81 (d, 2H), 3.30-3.53 (m, 1H), 3.53- 3.81 (m, 1H), 6.82 (s, 2H), 6.96 (dd, 1H), 8.07 (dd, 2H) A150 1H NMR (500 MHz, CDCl.sub.3) δ (delta) 1.62-1.93 (m, 1H), 1.93- 2.09 (m, 7H), 2.19 (s, 4H), 2.56- 2.85 (m, 2H), 3.37-3.71 (m, 2H), 6.78 (s, 2H), 8.05 (d, 1H), 8.18- 8.36 (m, 1H), 8.61 (d, 1H) A151 1H NMR (500 MHz, CDCl.sub.3) δ (delta) 1.70-2.39 (m, 12H), 2.57- 2.98 (m, 2H), 3.33-3.66 (m, 1H), 3.70-4.01 (m, 1H), 6.83 (s, 2H), 7.30-7.41 (m, 1H), 7.41-7.58 (m, 1H), 8.18-8.38 (m, 1H), 8.39-8.59 (m, 1H) A152 0 1H NMR (500 MHz, CDCl.sub.3) δ (delta) 1.68-2.10 (m, 8H), 2.22- 2.35 (s, 4H), 2.57-2.98 (m, 2H), 3.21-3.52 (m, 1H), 3.52-3.69 (m, 1H), 6.82 (s, 2H), 7.29-7.82 (m, 3H), 8.52-8.75 (m, 1H) A153 1H NMR (500 MHz, CDCl.sub.3) δ (delta) 1.81-2.25 (m, 11H), 2.25- 2.48 (m, 1H), 2.73-2.88 (m, 1H), 2.88-3.05 (m, 1H), 3.25- 3.51 (m, 1H), 3.63-3.85 (m, 1H), 6.79 (d, 2H), 8.07-8.48 (m, 3H), 8.80 (d, 1H) A154 1H NMR (500 MHz, CDCl.sub.3) δ (delta) 1.60-2.56 (m, 8H), 2.58- 3.12 (m, 2H), 3.29-3.69 (m, 2H), 3.87-4.27 (m, 1H), 7.29 (br. s., 2H), 7.59 (s, 2H), 7.85 (s, 1H), 8.24-8.47 (m, 2H), 8.47-8.78 (m, 1H) A155 1H NMR (500 MHz, CDCl.sub.3) δ (delta) 1.56-2.33 (m, 9H), 2.56- 3.05 (m, 2H), 3.4-3.6 (br. s., 1.5H), 3.76-4.07 (m, 0.5H), 7.07- 7.36 (m, 2H), 7.56 (s, 1H), 7.66- 7.89 (m, 2H), 8.09 (d, 1H), 8.33- 8.76 (m, 2H) A156 1H NMR (400 MHz, CDCl.sub.3) δ (delta) 1.68-2.4 (m, 9H), 2.4-2.6 (s, 3H), 2.97 (d, 2H), 3.26-3.65 (m, 1H), 3.86-4.18 (m, 1H), 7.15- 7.49 (m, 3H), 7.61 (br. s., 1H), 7.86 (br. s., 1H), 8.04 (br. s., 1H), 8.25-8.63 (m, 1H), 8.63-8.98 (m, 1H) A157 1H NMR (500 MHz, CDCl.sub.3) δ (delta) 1.76-1.97 (m, 2H), 1.97- 2.10 (m, 6H), 2.18 (s, 3H), 2.24- 2.50 (m, 1H), 2.59-3.09 (m, 2H), 3.16-3.58 (m, 1H), 3.59-3.73 (m, 1H), 6.76 (d, 2H), 7.92-8.58 (m, 3H), 8.74 (d, 1H) A158 1H NMR (500 MHz, CDCl.sub.3) δ (delta) 1.54-2.53 (m, 12H), 2.55- 3.18 (m, 2H), 3.18-3.67 (m, 1H), 3.63-3.89 (m, 1H), 6.83 (d, 2H), 6.87-6.95 (m, 1H), 8.17-8.32 (m, 1H), 8.58-8.00 (m, 1H) A159 1H NMR (500 MHz, d4-methanol) δ (delta) 6.89 (2H, s), 3.87 (3H, s), 3.61-3.99 (2H, m), 3.01-2.92 (1H, m), 2.88 (1H, br), 2.51 (1H, d) 2.28 (3H, s), 2.24-2.14 (1H, m), 2.07 (6H, s), 1.79-1.69 (1H, m) A160 1H NMR (500 MHz, d4-methanol) δ (delta) 6.74 (2H, s), 3.76 (3H, s), 3.39 (t, 2H), 2.87-2.78 (1H, m), 2.73-2.64 (br. m, 1H), 2.38 (1H, d) 2.15 (3H, s), 2.12 (3H, s), 2.09- 2.02 (1H, m), 1.94 (6H, s), 1.64- 1.06 (1H, m) A161 1H NMR (500 MHz, d4-methanol) δ (delta) 6.74 (2H, s), 3.92 (3H, s), 3.51-3.41 (2H, m), 2.88-2.80 (1H, m), 2.75-2.68 (1H, br. m), 2.38 (1H, d), 2.14 (3H, s), 2.13- 2.04 (1H, m), 1.93 (6H, s), 1.68- 1.58 (1H, m) A162 0 1H NMR (500 MHz, d4-methanol) δ (delta) 6.74 (2H, s), 6.26 (1H, s), 3.47-3.34 (2H, m), 2.86-2.77 (1H, m), 2.70-2.62 (1H, br. m), 2.37 (1H, d), 2.13 (3H, s), 2.10- 2.00 (2H, m), 1.93 (6H, s), 1.63- 1.53 (1H, m), 1.04-0.98 (2H, m), 0.88-0.81 (2H, m) A163 1H NMR (500 MHz, d4-methanol) δ (delta) 6.77 (2H, s), 3.70 (3H, s), 3.49-3.37 (2H, m), 2.87-2.79 (1H, m), 2.72-2.65 (1H, br. m), 2.38 (1H, d), 2.19 (3H, s), 2.15 (3H, s), 2.12-2.02 (1H, m), 1.94 (6H, s), 1.65-1.55 (1H, m) A164 1H NMR (500 MHz, d4-methanol) δ (delta) 6.74 (2H, s), 3.49 (2H, t), 2.88-2.81 (1H, m), 2.79 (3H, s), 2.76-2.69 (1H, br. m), 2.40 (1H, d) 2.17-2.08 (1H, m), 2.13 (3H, s), 1.93 (6H, s), 1.70-1.61 (1H, m) A165 1H NMR (500 MHz, CDCl.sub.3) δ (delta) 1.89-2.03 (m, 1H), 2.17 (br. s., 2H), 2.84-3.05 (m, 2H), 3.33-3.55 (m, 1H), 4.12-4.28 (m, 1H), 7.13 (s, 2H), 7.51 (s, 4H), 7.96-8.21 (m, 3H), 8.28- 8.48 (m, 1H) A166 1H NMR (500 MHz, CDCl.sub.3) δ (delta) 1.71-1.89 (m, 1H), 1.89- 2.27 (m, 10H), 2.42 (dd, 1H), 2.65-2.99 (m, 2H), 3.50-3.66 (m, 2H), 6.86 (s, 2H), 6.97 (dd, 1H), 7.77-7.97 (m, 1H), 8.50 (d, 1H) A167 1H NMR (500 MHz, CDCl.sub.3) δ (delta) 1.73-2.02 (m, 8H), 2.11- 2.35 (m, 4H), 2.42-2.60 (m, 3H), 2.61-2.93 (m, 2H), 3.25-3.74 (m, 2H), 6.79 (s, 2H), 7.06 (d, 1H), 7.62-7.85 (m, 2H) A168 1H NMR (500 MHz, CDCl.sub.3) δ (delta) 2.00 (d, 8H), 2.20 (s, 4H), 2.60-2.93 (m, 2H), 3.29-3.49 (m, 1H), 3.49-3.73 (m, 1H), 6.79 (s, 2H), 7.20 (dd, 1H), 7.78 (d, 2H), 8.29 (dd, 1H) A169 1H NMR (500 MHz, CDCl.sub.3) δ (delta) 1.90-2.54 (m, 9H), 2.81- 3.10 (m, 2H), 3.39-4.06 (m, 2H), 7.19-7.40 (m, 2H), 7.59 (s, 1H), 7.78-7.90 (m, 1H), 7.93-8.46 (m, 2H), 8.58-8.88 (m, 1H) A170 1H NMR (500 MHz, d4-methanol) δ (delta) 1.74-1.86 (m, 1H), 2.18 (s, 6H), 2.20-2.28 (m, 1H), 2.56 (dd, 1H), 2.83-2.91 (m, 1H), 3.00 (dd, 1H), 3.56-3.67 (m, 2H), 7.49 (s, 2H), 7.52 (dd, 1H), 7.94 (t, 1H), 8.09 (d, 1H), 8.58 (s, 1H), 8.61 (d, 1H) A171 1H NMR (500 MHz, d4-methanol) δ (delta) 1.75-1.85 (m, 1H), 2.20 (s, 6H), 2.22-2.28 (m, 1H), 2.51- 2.60 (m, 1H), 2.81-2.91 (m, 1H), 2.95-3.05 (m, 1H), 3.57-3.67 (m, 2H), 7.51-7.57 (m, 3H), 7.87 (d, 1H), 7.95 (td, 1H), 8.10 (d, 1H), 8.49 (d, 1H), 8.63 (d, 1H) A172 0 1H NMR (500 MHz, d4-methanol) δ (delta) 6.75 (2H, s), 3.52-3.38 (2H, m), 2.89-2.79 (1H, m), 2.74- 2.65 (1H, br. m), 2.38 (1H, d), 2.14 (3H, s), 2.12-2.02 (1H, m), 1.95 (6H, s), 1.69-1.57 (1H, m) A173 1H NMR (500 MHz, d4-methanol) δ (delta) 6.97 (1H, s), 6.73 (2H, s), 4.04 (3H, s), 3.38 (2H, t), 2.88- 2.78 (1H, m), 2.72-2.63 (1H, br. m), 2.37 (1H, d), 2.13 (3H, s), 2.11-2.01 (1H, m), 1.93 (6H, s), 1.68-1.53 (1H, m) A174 1H NMR (500 MHz, d4-methanol) δ (delta) 6.74 (2H, s), 4.49 (2H, s), 3.39 (2H, t), 3.34 (3H, s), 2.88- 2.78 (1H, m), 2.72-2.62 (1H, m), 2.62-2.52 (1H, m), 2.37 (1H, d) 2.13 (3H, s), 2.10-2.01 (1H, m), 1.94 (6H, s), 1.68-1.56 (1H, m), 0.89 (4H, d) A175 1H NMR (400 MHz, d4-methanol) δ (delta) 1.66-1.84 (m, 2H), 2.24 (d, 6H), 2.73 (s, 2H), 3.27-3.39 (m, 1H), 3.55-3.65 (m, 2H), 6.95- 7.10 (m, 1H), 7.29 (br. s., 3H), 7.37-7.48 (m, 2H), 7.50-7.68 (m, 1H), 7.89-7.99 (m, 1H), 8.06- 8.24 (m, 1H), 8.49-8.79 (m, 1H) A176 1H NMR (500 MHz, d4-methanol) δ (delta) 1.77 (ddt, 1H), 2.19 (s, 7H), 2.42 (dd, 1H), 2.63-2.96 (m, 2H), 3.55-3.75 (m, 3H), 7.18- 7.63 (m, 6H), 7.86-8.01 (m, 1H), 8.10 (d, 1H), 8.50-8.78 (m, 1H) A177 1H NMR (400 MHz, d4-methanol) δ (delta) 6.73 (2H, s), 3.72 (3H, s), 3.43-3.35 (2H, m), 2.87-2.79 (1H, m), 2.73-2.64 (1H, br. m), 2.38 (1H, d), 2.17 (3H, s), 2.13 (3H, s), 2.09-2.00 (1H, m), 1.93 (6H, s), 1.65-1.54 (1H, m) A178 1H NMR (400 MHz, d4-methanol) δ (delta) 6.74 (2H, s), 3.38 (2H, t), 2.87-2.78 (1H, m), 2.72-2.63 (1H, br. s), 2.38 (1H, d), 2.37 (3H, s), 2.29 (3H, s), 2.13 (3H, s), 2.10- 2.00 (1H, m), 1.92 (6H, s), 1.66- 1.53 (1H, m) A179 A180 A181 1H NMR (400 MHz, d4-methanol) δ 8.02 (1H, s), 6.72 (2H, s), 3.38 (2H, t), 2.87-2.77 (1H, m), 2.72- 2.61 (1H, m), 2.36 (1H, d), 2.33 (3H, s), 2.12 (3H, s), 2.08-1.99 (1H, m), 1.92 (6H, s), 1.64-1.52 (1H, m) A182 00 1H NMR (400 MHz, d4-methanol) δ 6.73 (2H, s), 3.35 (2H, t), 2.87- 2.78 (1H, m), 2.70-2.61 (1H, m), 2.53 (3H, s), 2.45 (3H, s), 2.36 (1H, d), 2.12 (3H, s), 2.07-1.98 (1H, m), 1.93 (6H, s), 1.65-1.53 (1H, m) A183 01 1H NMR (400 MHz, d4-methanol) δ 7.33 (1H, t), 6.88 (2H, s), 3.51 (2H, t), 3.00-2.90 (1H, m), 2.83- 2.72 (1H, m), 2.74 (3H, s), 2.49 (1H, d), 2.26 (3H, s), 2.22-2.11 (1H, m), 2.04 (6H, s), 1.79-1.67 (1H, m) A184 02 1H NMR (400 MHz, CD.sub.3OD) δ 1.66-1.86 (m, 1H), 2.19-2.26 (m, 6H), 2.33 (dd, 1H), 2.61-2.79 (m, 2H), 3.33 (dt, 1H), 3.63 (t, 2H), 7.10 (s, 2H), 7.26-7.37 (m, 3H), 7.43-7.49 (m, 1H), 7.54 (ddd, 1H), 7.96 (td, 1H), 8.11 (d, 1H), 8.65 (d, 1H) A185 03 1H NMR (400 MHz, CD.sub.3CN) δ 1.68-1.86 (m, 1H), 1.91-2.12 (m, 7H), 2.24 (s, 4H), 2.68-2.92 (m, 2H), 3.35-3.68 (m, 2H), 6.85 (s, 2H), 7.95 (dd, 1H), 8.13-8.34 (m, 1H), 8.46-8.60 (m, 1H) A186 04 1H NMR (400 MHz, CD.sub.3CN) δ 1.73-1.90 (m, 1H), 1.93-2.13 (m, 7H), 2.26 (s, 4H), 2.67-2.92 (m, 2H), 3.37-3.74 (m, 2H), 6.87 (s, 2H), 7.74 (t, 1H), 8.10 (d, 1H), 8.21-8.53 (m, 1H) A187 05 1H NMR (400 MHz, CDCl.sub.3) δ 1.80 (m, 1H), 1.90-2.47 (m, 11H), 2.65-2.98 (m, 2H), 3.50 (s, 2H), 6.89 (s, 2H), 7.98 (dd, 2H), 8.48 (d, 1H) A188 06 1H NMR (400 MHz, CD.sub.3CN) δ 8.47 (d, 2H), 8.15 (d, 1H), 7.70 (dd, 1H), 6.69-7.19 (m, 3H), 3.58- 3.80 (m, 1H), 3.39-3.58 (m, 1H), 2.80 (br. s., 2H), 2.26 (s, 4H), 1.73-2.13 (m, 8H) A189 07 1H NMR (400 MHz, CD.sub.3CN) δ 8.36-8.54 (m, 1H), 8.13-8.36 (m, 1H), 7.73-7.89 (m, 1H), 6.85 (s, 2H), 3.26-3.73 (m 2H), 2.63-2.92 (m, 2H), 2.24 (s, 4H), 1.93-2.11 (m, 7H), 1.70-1.86 (m, 1H) A190 08 1H NMR (400 MHz, CDCl.sub.3) δ 8.48 (s, 2H), 8.13 (d, 1H), 7.84 (dd, 1H), 6.86 (s, 2H), 5.25-5.48 (m, 1H), 3.73-4.06 (m, 1H), 3.48 (br. s., 1H), 2.74-2.97 (m, 2H), 1.74-2.37 (m, 12H) A191 09 1H NMR (400 MHz, CDCl.sub.3) δ 8.28 (s, 1H), 7.93 (d, 1H), 7.79 (s, 1H), 7.45-7.65 (m, 2H), 7.14 (s, 2H), 3.30-3.81 (m, 2H), 2.87 (dd, 2H), 2.28 (d, 1H), 1.80-2.14 (m, 8H) A192 0 1H NMR (400 MHz, CDCl.sub.3) δ 8.34-8.79 (m, 2H), 7.55-8.19 (m, 2H), 6.61-6.97 (m, 2H), 2.54-4.07 (m, 4H), 1.61-2.35 (m, 15H) A193 1H NMR (400 MHz, CD.sub.3OD) δ 8.38 (d, 1H), 7.80 (d, 1H), 6.84 (s, 2H), 3.41-3.63 (m, 2H), 2.86-3.03 (m, 1H), 2.70-2.86 (m, 1H), 2.34- 2.56 (m, 1H), 2.23 (s, 4H), 2.04 (d, 6H), 1.61-1.83 (m, 1H) A194 1H NMR (400 MHz, CDCl.sub.3) δ 8.32-8.57 (m, 2H), 8.05-8.26 (m, 1H), 6.79 (s, 2H), 3.57-3.84 (m, 1H), 3.36-3.57 (m, 1H), 2.62-2.89 (m, 2H), 2.20 (m, 4H), 1.94-2.14 (m, 7H), 1.88 (m, 1H) A195 1H NMR (400 MHz, CDCl.sub.3) δ 9.07 (d, 1H), 8.51 (d, 1H), 8.01- 8.29 (m, 1H), 6.82 (s, 2H), 3.63- 3.81 (m, 1H), 3.46-3.63 (m, 1H), 2.65-2.92 (m, 2H), 2.23-2.35 (m, 1H), 2.21 (s, 3H), 2.05 (d, 7H), 1.75-1.97 (m, 1H) A196 1H NMR (400 MHz, CDCl.sub.3) δ 9.16 (s, 1H), 8.65 (s, 1H), 7.90- 8.22 (m, 1H), 6.81 (s, 2H), 3.48- 3.75 (m, 2H), 2.64-2.94 (m, 2H), 2.25-2.39 (m, 1H), 2.20 (s, 3H), 2.05 (s, 7H), 1.70-1.92 (m, 1H) A197 1H NMR (400 MHz, CDCl.sub.3) δ 1.79-1.89 (m, 1H), 2.11-2.28 (m, 5H), 2.80-3.02 (m, 2H), 3.43 (d, 1H), 4.15 (s, br, 1H), 7.34 (d, 1H), 7.53 (dd, 1H), 7.62 (s, 1H), 7.88- 7.98 (m, 1H), 8.21 (d, 1H), 1.85 (m, 1H), 8.72 (br. s., 1H) A198 1H NMR (400 MHz, CDCl.sub.3) δ 8.70-8.53 (m, 2H), 8.26-8.13 (m, 1H), 7.91 (dd, 1H), 7.60-7.44 (m, 4H), 4.14-3.95 (m, 1H), 3.88-3.70 (m, 1H), 3.50-3.27 (m, 1H), 2.80 (d, 1H), 2.27 (d, 1H), 2.22 (s, 3H), 2.18-2.00 (m, 2H) A199 1H NMR (400 MHz, d4-methanol) δ 8.57 (s, 1H), 8.00 (d, 1H), 7.88 (d, 1H), 7.31 (s, 1H), 7.21 (s, 1H), 3.53-3.41 (m, 2H), 2.90-2.77 (m, 1H), 2.76-2.68 (m, 1H), 2.46-2.37 (m, 1H), 2.14-2.01 (m, 1H), 2.02 (s, 3H), 1.74-1.58 (m, 1H) A200 1H NMR (400 MHz, CD.sub.3OD) δ 1.64-1.90 (m, 1H), 2.14-2.38 (m, 2H), 2.61-2.82 (m, 2H), 3.55-3.65 (m, 2H), 6.93-7.07 (m, 1H), 7.22 (d, 2H), 7.47-7.61 (m, 1H), 7.90- 8.01 (m, 1H), 8.05-8.15 (m, 1H), 8.57-8.74 (m, 1H) A201 1H NMR (400 MHz, CD.sub.3OD) δ 1.68-1.89 (m, 1H), 2.10-2.22 (m, 1H), 2.24-2.36 (m, 1H), 2.58-2.81 (m, 2H), 3.79-3.85 (m, 2H), 6.89- 7.08 (m, 2H), 7.15-7.28 (m, 2H), 7.43 (d, 1H), 7.69 (dd, 1H) A202 0 1H NMR (400 MHz, CD.sub.3OD) δ 8.62 (s, 1H), 8.12 (d, 1H), 8.00 (t, 1H), 7.76 (d, 1H), 7.71-7.53 (m, 2H), 3.68-3.53 (m, 2H), 3.03-2.40 (m, 1H), 2.40-2.80 (m, 1H), 2.53 (d, 1H), 2.27-2.13 (m, 1H), 1.89- 1.73 (m, 1H) A203 1H NMR (400 MHz, CD.sub.3OD) δ 1.66-1.84 (m, 1H), 2.24 (d, 6H), 2.28-2.39 (m, 1H), 2.58-2.69 (m, 1H), 2.71-2.82 (m, 1H), 3.30-3.34 (m, 1H), 3.62 (t, 2H), 7.28 (s, 2H), 7.36 (t, 1H), 7.48-7.60 (m, 3H), 7.95 (td, 1H), 8.11 (d, 1H), 8.64 (d, 1H) A204 1H NMR (400 MHz, CD.sub.3OD) δ 1.66-1.85 (m, 1H), 2.16-2.25 (m, 7H), 2.29-2.42 (m, 3H), 2.60-2.82 (m, 2H), 3.54-3.73 (m, 3H), 7.15- 7.63 (m, 7H), 7.96 (td, 1H), 8.11 (d, 1H), 8.65 (d, 1H) A205 1H NMR (400 MHz, d4-methanol) δ 9.39-9.27 (m, 1H), 9.13-8.93 (m, 1H), 8.24-8.07 (m, 1H), 6.86 (s, 2H), 3.71-3.53 (m, 2H), 3.03- 2.87 (m, 1H), 2.87-2.74 (m, 1H), 2.59-2.44 (m, 1H), 2.25 (s, 4H), 2.04 (s, 7H), 1.85-1.69 (m, 1H) A206 1H NMR (400 MHz, d4-methanol) δ 8.97 (s, 2H), 6.86 (s, 2H), 3.72- 3.51 (m, 2H), 3.02-2.87 (m, 1H), 2.87-2.69 (m, 1H), 2.60-2.40 (m, 1H), 2.25 (s, 4H), 2.09-1.95 (m, 7H), 1.84-1.65 (m, 1H) A207 1H NMR (400 MHz, d4-methanol) δ 9.96-9.83 (m, 1H), 9.75-9.67 (m, 1H), 8.83-8.58 (m, 1H), 6.87 (s, 2H), 3.71-3.54 (m, 2H), 3.08- 2.93 (m, 1H), 2.93-2.77 (m, 1H), 2.60-2.40 (m, 1H), 2.25 (s, 4H), 2.12-1.96 (m, 7H), 1.88-1.69 (m, 1H) A208 1H NMR (400 MHz, d4-methanol) δ 8.90 (d, 1H), 8.01 (d, 1H), 6.85 (s, 2H), 3.58 (s, 2H), 3.02-2.87 (m, 1H), 2.87-2.68 (m, 1H), 2.56- 2.46 (m, 1H), 2.24 (s, 4H), 2.09- 1.97 (m, 7H), 1.82-1.67 (m, 1H) A209 1H NMR (400 MHz, d4-methanol) δ 8.36-8.24 (m, 1H), 8.08-7.73 (m, 1H), 6.88 (s, 2H), 3.73-3.48 (m, 2H), 3.05-2.89 (m, 1H), 2.89- 2.72 (m, 1H), 2.63-2.41 (m, 1H), 2.27 (s, 4H), 2.11-1.95 (m, 7H), 1.86-1.68 (m, 1H) A210 1H NMR (400 MHz, d4-methanol) δ 9.64-9.39 (m, 1H), 8.72-8.55 (m, 1H), 8.43-8.00 (m, 1H), 6.96- 6.61 (m, 2H), 3.70-3.60 (m, 2H), 3.02-2.90 (m, 1H), 2.90- 2.77 (m, 1H), 2.63-2.42 (m, 1H), 2.25 (s, 4H), 2.12-1.98 (m, 7H), 1.84-1.70 (m, 1H) A211 1H NMR (400 MHz, d4-methanol) δ (delta) 8.86 (d, 1H), 8.60 (dd, 1H), 8.49 (d, 1H), 8.39 (s, 1H), 8.08 (dd, 1H), 7.70 (s, 1H), 7.67 (d, 1H), 7.54 (dd, 1H), 7.14 (d, 1H), 3.73-3.63 (m, 2H), 3.01 (dd, 1H), 2.91-2.80 (m, 1H), 2.58 (dd, 1H), 2.57 (quart, 2H), 2.30-2.20 (m, 1H), 1.93-1.78 (m, 1H), 1.16 (t, 3H) A212 0 1H NMR (400 MHz, d4-methanol) δ (delta) 6.76 (2H, s), 3.54-3.42 (2H, m), 2.90-2.77 (1H, m), 2.75- 2.66 (1H, m), 2.39 (1H, d), 2.14 (3H, s), 2.12-2.03 (1H, m), 1.95 (6H, s), 1.72-1.61 (1H, m) A213 1H NMR (400 MHz, d-4 methanol) δ (delta) 6.76 (2H, s), 3.47-3.33 (2H, m), 2.85-2.78 (1H, m), 2.71-2.63 (1H, m), 2.35 (1H, d), 2.14 (3H, s), 2.10-2.02 (1H, m), 1.95 (6H, s), 1.64-1.54 (1H, m)

(189) Additional compounds in Table P1 below illustrate the present invention, and are particular embodiments of the compounds of formula (I) according to the present invention, in which G is not hydrogen. 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 and with any appropriate and/or necessary process changes.

(190) It should be noted that certain compounds of the invention exist as a mixture of isomers, including atropisomers, 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 were recorded at ambient temperature.

(191) TABLE-US-00014 TABLE P1 Compound number Structure Data P1  1H NMR (500 MHz, CDCl.sub.3) δ ppm 1.84-2.02 (m, 1H), 2.06- 2.37 (m, 7H), 2.88-3.21 (m, 2H), 3.32-3.88 (m, 3H), 7.20-7.42 (m, 2H), 7.48-7.98 (m, 5H), 8.04- 8.23 (m, 2H), 8.39-8.74 (m, 2H) P2  1H NMR (400 MHz, CDCl.sub.3) δ ppm 1.28-1.50 (m, 3H), 1.65- 1.97 (m, 2H), 2.12-2.28 (m, 7H), 2.54-2.99 (m, 3H), 3.01-3.39 (m, 1H), 3.64-3.81 (m, 4H), 5.56- 6.36 (m, 1H), 7.33 (br. s., 3H), 7.88 (s, 2H), 8.20 (s, 2H), 8.44- 8.66 (m, 1H) P3  1H NMR (400 MHz, CDCl.sub.3) δ ppm 8.47-8.70 (m, 1H), 7.88- 8.23 (m, 3H), 6.73-6.95 (m, 2H), 5.71-6.32 (m, 1H), 3.52-3.83 (m, 4H), 2.33-3.30 (m, 3H), 2.27 (s, 4H), 1.98-2.10 (m, 6H), 1.67- 1.91 (m, 2H), 1.30-1.57 (m, 3H) P4  1H NMR (400 MHz, CDCl.sub.3) δ ppm 8.55 (d, 1H), 8.19 (d, 2H), 7.75-7.95 (m, 2H), 7.61 (s, 1H), 7.39-7.52 (m, 1H), 7.33 (s, 2H), 3.53-3.86 (m, 2H), 3.32-3.53 (m, 1H), 2.77-3.02 (m, 4H), 2.21- 2.36 (m, 1H), 2.09-2.21 (m, 6H), 1.83-1.93 (m, 1H), 1.19- 1.36 (m, 3H) P5  1H NMR (400 MHz, CDCl.sub.3) δ ppm 8.46-8.60 (m, 1H), 8.09- 8.29 (m, 2H), 7.75-7.95 (m, 2H), 7.55-7.68 (m, 1H), 7.41-7.51 (m, 1H), 7.29-7.37 (m, 2H), 3.57- 3.75 (m, 2H), 3.32-3.51 (m, 1H), 2.87-3.11 (m, 1H), 2.65- 2.81 (m, 2H), 2.45-2.63 (m, 1H), 2.17 (d, 7H), 1.68-1.86 (m, 1H), 1.14 (s, 3H) P6  1H NMR (400 MHz, CDCl.sub.3) δ ppm 8.45-8.64 (m, 1H), 8.19 (d, 2H), 7.77-7.97 (m, 2H), 7.61 (s, 1H), 7.30-7.50 (m, 3H), 4.14- 4.26 (m, 2H), 3.54-3.87 (m, 2H), 3.41 (dd, 1H), 2.97 (dd, 2H), 2.09- 2.38 (m, 7H), 1.82-1.98 (m, 1H), 1.27 (q, 3H) P7  1H NMR (400 MHz, CDCl.sub.3) δ ppm 8.56 (dd, 1H), 8.19 (d, 2H), 7.75-7.96 (m, 2H), 7.62 (s, 1H), 7.39-7.51 (m, 1H), 7.33 (s, 2H), 3.52-3.88 (m, 2H), 3.20-3.40 (m, 1H), 2.87 (m, 2H), 2.36 (t, 2H), 2.08-2.31 (m, 7H), 1.79- 1.96 (m, 1H), 1.43-1.60 (m, 2H), 1.10-1.30 (m, 2H), 0.82 (t, 3H) P8  1H NMR (400 MHz, CDCl.sub.3) δ ppm 8.49-8.62 (m, 1H), 8.19 (d, 2H), 7.77-7.92 (m, 2H), 7.62 (s, 1H), 7.40-7.51 (m, 1H), 7.33 (s, 2H), 3.50-3.87 (m, 2H), 3.20- 3.36 (m, 1H), 2.75-2.95 (m, 2H), 2.21-2.37 (m, 1H), 2.15 (d, 6H), 1.78-1.98 (m, 1H), 1.10 (s, 9H) P9  0 1H NMR (400 MHz, CDCl.sub.3) δ ppm 8.53-8.67 (m, 1H), 7.89- 8.23 (m, 3H), 6.86 (s, 2H), 3.72 (s, 2H), 3.35 (dd, 1H), 2.73-2.99 (m, 4H), 2.26 (s, 4H), 1.97-2.11 (m, 6H), 1.78-1.94 (m, 1H), 1.18- 1.32 (m, 3H) P10 1H NMR (400 MHz, CDCl.sub.3) δ ppm 8.61 (d, 1H), 7.87-8.18 (m, 3H), 6.85 (s, 2H), 3.51-3.68 (m, 2H), 3.37-3.50 (m, 1H), 2.90- 3.05 (m, 1H), 2.75 (m, 2H), 2.41- 2.57 (m, 1H), 2.16-2.35 (m, 4H), 1.99-2.14 (m, 6H), 1.66-1.84 (m, 1H), 1.13 (t, 3H) P11 1H NMR (400 MHz, CDCl.sub.3) δ ppm 8.60 (d, 1H), 7.88-8.22 (m, 3H), 6.87 (s, 2H), 4.19 (q, 2H), 3.53-3.83 (m, 2H), 3.36 (dd, 1H), 2.92 (dd, 2H), 2.26 (s, 4H), 1.97- 2.15 (m, 6H), 1.79-1.95 (m, 1H), 1.21-1.35 (m, 3H) P12 1H NMR (400 MHz, CDCl.sub.3) δ ppm 8.60 (d, 1H), 7.90-8.26 (m, 3H), 6.86 (s, 2H), 3.48-3.88 (m, 2H), 3.27 (dd, 1H), 2.67-2.92 (m, 2H), 2.14-2.41 (m, 6H), 1.96- 2.11 (m, 6H), 1.78-1.93 (m, 1H), 1.43-1.58 (m, 2H), 1.10-1.31 (m, 2H), 0.82 (t, 3H) P13 1H NMR (400 MHz, CDCl.sub.3) δ ppm 8.54-8.67 (m, 1H), 7.87- 8.22 (m, 3H), 6.71-6.90 (m, 2H), 3.47-3.85 (m, 2H), 3.11-3.34 (m, 1H), 2.63-2.92 (m, 2H), 2.25 (m, 4H), 1.97-2.13 (m, 6H), 1.76- 1.94 (m, 1H), 1.09 (s, 9H) P14 1H NMR (400 MHz, CDCl.sub.3) δ ppm 8.45-8.66 (m, 1H), 8.09- 8.36 (m, 2H), 7.79-7.98 (m, 4H), 7.61 (s, 1H), 7.39-7.50 (m, 1H), 7.29-7.38 (m, 2H), 7.01-7.18 (m, 2H), 3.40-3.90 (m, 3H), 2.83- 3.17 (m, 2H), 2.20 (d, 7H), 1.80- 2.01 (m, 1H) P15 1H NMR (400 MHz, CDCl.sub.3) δ ppm 0.71-0.86 (m, 3H), 1.18- 1.40 (m, 2H), 1.55-1.71 (m, 2H), 1.91 (br. s., 1H), 2.07-2.37 (m, 7H), 2.75-3.22 (m, 4H), 3.47 (dd, 1H), 3.56-3.84 (m, 2H), 7.29- 7.49 (m, 3H), 7.55-7.65 (s, 1H), 7.77-7.97 (m, 2H), 8.07-8.36 (m, 2H), 8.46-8.62 (m, 1H) P16 1H NMR (400 MHz, CDCl.sub.3) δ ppm 8.46-8.67 (m, 1H), 8.20 (d, 2H), 7.87 (s, 2H), 7.74 (dd, 2H), 7.63 (s, 1H), 7.38-7.49 (m, 1H), 7.26 (d, 2H), 7.03-7.18 (m, 2H), 3.52-3.83 (m, 2H), 3.32-3.52 (m, 1H), 2.79-3.05 (m, 2H), 2.15- 2.31 (m, 1H), 1.95-2.08 (m, 6H), 1.80-1.95 (m, 1H) P17 1H NMR (400 MHz, CDCl.sub.3) δ ppm 8.60 (d, 1H), 8.02-8.24 (m, 2H), 7.86-8.02 (m, 3H), 7.10 (t, 2H), 6.86 (s, 2H), 3.55-3.87 (m, 2H), 3.35-3.55 (m, 1H), 2.78- 3.16 (m, 2H), 2.25 (m, 4H), 2.01- 2.19 (m, 6H), 1.84-2.00 (m, 1H) P18 1H NMR (400 MHz, CDCl.sub.3) δ ppm 8.60 (d, 1H), 7.89-8.22 (m, 3H), 6.88 (s, 2H), 3.50-3.84 (m, 2H), 3.26-3.47 (m, 1H), 2.78- 3.05 (m, 4H), 2.27 (s, 4H), 1.97- 2.13 (m, 6H), 1.79-1.97 (m, 1H), 1.55 (s, 2H), 1.20 (d, 2H), 0.78 (t, 3H) P19 0 1H NMR (400 MHz, CDCl.sub.3) δ ppm 8.60 (d, 1H), 8.08 (d, 2H), 7.92-8.04 (m, 1H), 7.65 (dd, 2H), 7.04 (t, 2H), 6.75 (d, 2H), 3.49-3.80 (m, 2H), 3.26-3.44 (m, 1H), 2.71-2.97 (m, 2H), 2.25 (s, 4H), 1.90 (d, 7H) P20 1H NMR (400 MHz, CDCl.sub.3) δ ppm 8.50-8.70 (m, 1H), 7.86- 8.26 (m, 3H), 6.75-6.92 (m, 2H), 4.96-5.22 (m, 2H), 3.52-3.83 (m, 5H), 3.00-3.26 (m, 1H), 2.68- 2.79 (m, 1H), 2.15-2.32 (m, 4H), 1.97-2.13 (m, 6H), 1.70- 1.91 (m, 1H), 1.21-1.33 (m, 3H) P21 1H NMR (400 MHz, in solvent) δ ppm 1.68-1.97 (m, 4H), 2.13- 2.35 (m, 6H), 2.70-2.91 (m, 1H), 2.97-3.13 (m, 1H), 3.23 (s, 2H), 3.29-3.42 (m, 4H), 3.42-3.82 (m, 3H), 7.33 (m, 3H), 7.55-7.65 (s, 1H), 7.76-7.96 (m, 2H), 8.19 (d, 2H), 8.56 (d, 1H) P22 1H NMR (400 MHz, CDCl.sub.3) δ ppm 1.86 (d, 4H), 2.01-2.14 (m, 6H), 2.26 (s, 4H), 2.67-3.12 (m, 2H), 3.14-3.50 (m, 6H), 3.52- 3.84 (m, 2H), 6.86 (s, 2H), 7.85- 8.23 (m, 3H), 8.60 (d, 1H) P23 1H NMR (400 MHz, CDCl.sub.3) δ 8.49-8.40 (m, 1H), 8.24-8.12 (m, 2H), 7.50-7.39 (m, 1H), 6.88-6.76 (m, 2H), 3.84-3.49 (m, 2H), 3.33- 3.13 (m, 1H), 2.93-2.69 (m, 2H), 2.25 (s, 4H), 2.04 (d, 6H), 1.95- 1.76 (m, 1H), 1.09 (s, 9H) P24 1H NMR (400 MHz, CDCl.sub.3) δ 8.60-8.49 (m, 1H), 8.34-8.12 (m, 2H), 7.90-7.73 (m, 1H), 7.49-7.36 (m, 1H), 6.83 (s, 2H), 3.87-3.51 (m, 2H), 3.36-3.15 (m, 1H), 2.96- 2.62 (m, 2H), 2.25 (s, 4H), 2.04 (d, 6H), 1.94-1.79 (m, 1H), 1.08 (s, 9H) P25 1H NMR (400 MHz, CDCl.sub.3) δ 8.18-7.79 (m, 3H), 7.16-6.98 (m, 1H), 6.83 (s, 2H), 3.88-3.50 (m, 2H), 3.34-3.13 (m, 1H), 2.92-2.69 (m, 2H), 2.33-1.68 (m, 11H), 1.14- 0.99 (m, 9H) P26 1H NMR (400 MHz, CDCl.sub.3) δ 8.56 (d, 1H), 8.52 (d, 1H), 8.29- 8.22 (br, 1H), 8.19 (d, 1H), 7.85 (t, 1H), 7.72-7.67 (m, 1H), 7.60 (s, 2H), 7.48-7.41 (m, 2H), 3.83-3.72 (m, 1H), 3.66-3.56 (m, 1H), 3.35- 3.26 (m, 1H), 2.92-2.82 (m, 2H), 2.33-2.20 (m, 1H), 2.18 (d, 6H), 1.95-1.82 (m, 1H), 1.09 (s, 9H) P27 1H NMR (400 MHz, CDCl.sub.3) δ 8.54 (s, 1H), 8.49 (d, 1H), 8.22- 8.15 (br, 1H), 8.12 (d, 1H), 7.79 (t, 1H), 7.66-7.56 (m, 2H), 7.55 (s, 2H), 7.39-7.32 (m, 1H), 3.76-3.64 (m, 1H), 3.61-3.49 (m, 1H), 3.30- 3.19 (m, 1H), 2.87-2.75 (m, 2H), 2.28-2.13 (m, 1H), 2.10 (d, 6H), 1.88-1.75 (m, 1H), 1.01 (s, 9H) P28 1H NMR (400 MHz, CDCl3) δ 8.56 (d, 1H), 8.26 (br. s., 1H), 8.20 (d, 1H), 7.86 (dt, 1H), 7.58- 7.50 (m, 2H), 7.48-7.40 (m, 1H), 7.24 (d, 2H), 7.10 (t, 2H), 3.86- 3.58 (m, 2H), 3.33 (dd, 1H), 2.96- 2.83 (m, 2H), 2.53-2.38 (m, 2H), 2.30 (d, 1H), 2.14 (d, 2H), 1.90 (d, 1H), 1.14-1.04 (m, 12H) P29 0 1H NMR (400 MHz, CDCl.sub.3) δ 8.62-8.48 (m, 1H), 8.19 (d, 2H), 7.94-7.78 (m, 2H), 7.62 (s, 1H), 7.49-7.39 (m, 1H), 7.32 (s, 2H), 3.86-3.68 (m, 1H), 3.68-3.51 (m, 1H), 3.43-3.25 (m, 1H), 2.97- 2.72 (m, 2H), 2.34 (t, 3H), 2.15 (d, 6H), 1.97-1.75 (m, 1H), 1.66- 1.45 (m, 2H), 0.84 (t, 3H) P30 H NMR (400 MHz, CDCl.sub.3) δ 8.55 (d, 1H), 8.30-8.20 (m, 1H), 8.19 (d, 1H), 7.91 (s, 1H), 7.85 (dd, 1H), 7.63 (s, 1H), 7.57 (s, 1H), 7.48-7.38 (m, 2H), 7.07 (d, 1H), 3.82-3.69 (m, 1H), 3.68-3.57 (m, 1H), 3.29 (dd, 1H), 2.92-2.80 (m, 2H), 2.58-2.48 (m, 2H), 2.33-2.22 (m, 1H), 1.96-1.82 (m, 1H), 1.16 (t, 3H), 1.14 (s, 9H)

BIOLOGICAL EXAMPLES

Biological Example 1A

Test 1A—Glasshouse Assay for Herbicidal Activity

(192) Seeds of a variety of test species were sown in standard soil in pots. After cultivation for one day (pre-emergence) or after 8 days cultivation (post-emergence) under controlled conditions in a glasshouse (at 24/16° C., day/night; 14 hours light; 65% humidity), the plants were sprayed with an aqueous spray solution derived from the formulation of the technical active ingredient in acetone/water (50:50) solution containing 0.5% Tween 20 (polyoxyethelyene sorbitan monolaurate, CAS RN 9005-64-5). The test plants were then grown under controlled conditions in a glasshouse (at 24/16° C., day/night; 14 hours light; 65% humidity) and watered twice daily. 13 days after application of the test herbicide, for pre- and post-emergence, the test was evaluated visually for percentage phytotoxicity to the plant (where 100%=total damage to plant; 0%=no damage to plant).

Biological Example 1A

Post-emergence Herbicidal Activity

(193) Test Plants:

(194) Lolium perenne (LOLPE), Alopecurus myosuroides (ALOMY), Echinochloa crus-galli (ECHCG), and Avena fatua (AVEFA); these are all grassy monocotyledonous weeds.

Biological Example 1A

Table of Post-emergence Herbicidal Activity (% Phytotoxicity)

(195) TABLE-US-00015 Compound Application No Rate (g/ha) LOLPE ALOMY ECHCG AVEFA A1 250 100 80 100 90 A2 250 100 90 80 80 A3 250 100 90 100 100 A4 250 80 70 100 60 A5 250 70 50 60 30 A6 250 90 30 90 60 A7 250 60 60 90 50 A8 250 90 60 80 70 A9 250 80 60 70 50 A10 250 70 60 50 70 A11 250 100 70 100 70 A12 250 100 80 100 100 A13 250 90 70 100 70 A14 250 70 60 100 70 A15 250 90 60 100 90 A16 250 60 60 50 50 A17 250 100 80 100 90 A18 250 90 60 100 80 A19 250 100 80 100 70 A20 250 100 70 100 70 A21 250 100 90 100 90 A22 250 80 70 80 80 A23 250 90 90 100 90 A24 250 90 80 80 80 A25 250 60 50 80 40 A26 250 80 80 80 80 A27 250 70 80 100 90 A28 250 70 100 80 50 A29 250 80 80 80 90 A32 250 100 90 100 100 A33 250 100 90 100 100 A34 250 100 90 100 100 A35 250 60 80 40 40 A36 250 80 80 80 70 A37 250 90 100 80 80 A38 250 100 100 100 100 A39 250 100 100 100 100 A40 250 100 100 100 100 A41 250 70 70 60 70 A43 250 100 100 100 100 A44 250 100 100 100 90 A45 250 80 50 60 80 A46 250 100 60 90 70 A47 250 100 80 100 90 A48 250 100 100 100 90 A50 250 100 20 70 70 A51 250 100 100 90 90 A52 250 90 70 100 70 A53 250 100 80 100 90 A54 250 100 100 60 100 A55 250 90 80 90 60 A56 250 100 100 90 90 A57 250 100 100 100 100 A57A 250 90 100 90 90 A58 250 80 50 50 30 A59 250 80 60 30 60 A60 250 80 80 70 90 A61 250 100 90 70 60 A62 250 100 100 80 80 A63 250 100 90 90 90 A64 250 80 90 60 80 A65 250 80 100 80 70 A66 250 60 80 70 40 A69 250 60 50 30 70 A70 250 100 100 90 90 A71 250 100 100 80 90 A72 250 90 90 70 90 A73 250 80 90 90 90 A74 250 80 90 70 30 A75 250 90 90 90 90 A76 250 60 70 80 90 A77 250 90 70 90 90 A78 250 60 80 80 80 A79 250 70 80 70 80 A83 250 100 100 100 100 A84 250 100 100 100 100 A85 250 100 90 100 100 A86 250 100 100 100 100 A87 250 100 100 100 100 A88 250 100 80 100 90 A89 250 100 100 100 100 A89A 250 100 100 100 100 A91 250 80 80 80 80 A92 250 70 80 70 80 A93 250 70 70 50 40 A94 250 80 90 90 100 A96 250 100 100 100 100 A97 250 100 100 100 100 A102 250 100 100 100 100 A104 250 100 90 100 90 A105 250 90 40 100 90 test 1 A105 250 90 60 100 90 test 2 A106 250 100 90 100 100 A109 250 100 100 100 100 A110 250 100 90 100 100 A111 250 100 100 100 100 A114 250 100 100 100 100 A115 250 100 100 100 100 A116 250 100 90 100 100 A117 250 100 100 100 100 A118 250 100 100 100 100 A119 250 90 100 100 90 A120 250 100 100 100 90 A121 250 100 90 100 90 A122 250 100 100 100 90 A123 250 100 100 90 100 A124 250 100 100 100 100 A125 250 100 100 100 100 A126 250 100 100 100 100 A126A 250 90 90 90 90 A126B 250 90 90 100 90 A129 250 100 100 100 100 A130 250 80 30 80 80 A131 250 100 100 100 100 A132 250 100 100 100 100 A133 250 100 100 100 90 A134 250 100 100 100 100 A135 250 100 100 100 90 A136 250 100 100 100 90 A137 250 80 80 100 70 A138 250 100 100 100 90 A139 250 100 90 90 90 A140 250 100 90 100 100 A141 250 70 60 100 10 A141A 250 70 80 80 80 A142 250 100 100 100 90 A143 250 100 90 100 90 A144 250 90 30 100 90 A145 250 90 100 90 90 A146 250 70 60 100 40 A147 250 70 60 60 60 A148 250 90 70 90 90 A149 250 100 100 100 100 A150 250 80 70 80 90 A151 250 90 90 90 90 A152 250 70 80 80 70 A154 250 100 100 100 100 A155 250 100 100 100 100 A156 250 90 50 100 90 A157 250 70 70 90 70 A158 250 80 80 70 90 A159 250 100 100 90 90 A160 250 90 90 100 100 A161 250 100 90 100 100 A162 250 100 70 90 90 A164 250 90 90 100 100 A165 250 100 90 100 100 A166 250 90 80 60 90 A167 250 70 60 90 30 A168 250 70 60 80 80 A169 250 A170 250 90 90 100 100 test 1 A170 250 80 90 100 90 test 2 A171 250 10 0 60 10 A172 250 100 90 100 90 A173 250 100 100 100 100 test 1 A173 250 100 100 100 100 test 2 A174 250 100 90 90 100 test 1 A174 250 90 90 90 90 test 2 A177 250 90 100 100 90 A178 250 100 70 80 90 A179 250 70 70 80 100 A180 250 80 70 90 80 A181 250 90 80 80 100 A182 250 80 80 90 90 A183 250 90 60 90 60 A184 250 60 10 90 20 A185 250 100 90 100 100 A186 250 100 100 100 90 A187 250 100 90 100 90 A188 250 100 100 100 100 A189 250 100 100 100 100 A190 250 90 80 90 90 A191 250 90 100 100 100 A192 250 100 80 100 90 A193 250 100 90 90 90 A194 250 90 80 100 90 A195 250 60 30 80 30 A196 250 90 80 100 90 A197 250 60 90 100 70 A203 250 80 80 100 100 A204 250 100 90 100 90 A212 250 70 30 70 50 A213 250 60 10 50 10 P2 250 90 80 100 100 P3 250 100 90 100 100 P4 250 100 100 100 100 P6 250 100 100 100 100 P7 250 100 100 100 100 P8 250 100 100 100 100 P9 250 100 100 100 100 P10 250 100 100 100 100 P11 250 100 100 100 100 P12 250 100 100 100 100 P13 250 100 100 100 100 P14 250 100 100 100 100 P15 250 100 100 100 100 P16 250 100 100 100 90 P17 250 100 100 100 100 P18 250 100 100 100 90 P19 250 100 100 100 100 P20 250 100 100 100 100 P21 250 70 80 100 80 P22 250 100 90 100 100 Note: a hyphen (-) in the table above indicates that no measurement was made.

Biological Example 1A

Pre-emergence Herbicidal Activity

(196) Test plants: Lolium perenne (LOLPE), Alopecurus myosuroides (ALOMY), Echinochloa crus-galli (ECHCG), and Avena fatua (AVEFA); these are all grassy monocotyledonous weeds.

Biological Example 1A

Table of Pre-emergence Herbicidal Activity (% Phytotoxicity)

(197) Positive pre-emergence herbicidal results were obtained for many exemplified compounds of the present invention applied pre-emergence at 250 g/ha; but, for brevity, only some of these results are presented below.

(198) TABLE-US-00016 Compound Application No Rate (g/ha) LOLPE ALOMY ECHCG AVEFA A1 1000 100 90 100 70 A2 250 100 90 70 70 A3 250 100 90 100 90 A13 250 90 80 100 80 A19 250 100 90 100 50 A23 250 100 90 100 80 A32 250 100 100 100 80 A33 250 100 90 100 80 A34 250 100 90 100 100 A87 250 100 100 100 90 A89 250 100 100 100 100 A120 250 100 90 100 70 A145 250 100 90 90 40 A159 250 100 90 100 80 P8 250 100 90 100 90 P9 250 100 100 100 90

Biological Example 1B

Test 1B—Glasshouse Assay for Post-emergence Herbicidal Activity Against Grassy Monocotyledonous Weeds and Cereal Crops (Wheat and Barley)

(199) Biological Example 1B tests the herbicidal activity of“technical” compounds (i.e. compounds not previously formulated before the test), as the herbicides under test.

(200) An “instant formulation”, known as the “IF50”, containing 50 g/liter (i.e. 5% w/v) of the “technical” (i.e. unformulated) active ingredient (i.e. the herbicide under test), is prepared by dissolving the active ingredient in a mixture of organic solvents and emulsifier, details of which are provided in the Table below.

(201) TABLE-US-00017 TABLE Composition of the mixture of organic solvents and emulsifier used as a base for the instant formulation (IF50). CAS Chemical Registry Amount/ Component Supplier description number % w/w Emulsogen Clariant castor oil 61791-12-6 11.12 EL360 ™ ethoxylate (as emulsifier) N-methyl- widely 1-methyl-2- 872-50-4 44.44 pyrrolidone available pyrrolidone Dowanol DPM ™ Dow dipropylene 34590-94-8 44.44 glycol ether glycol mono- methyl ether

(202) This IF50 is mixed with a small, variable amount of acetone to aid dissolution, before addition of a 0.5% v/v aqueous solution of the adjuvant Adigor™ (an adjuvant containing rapeseed oil methyl ester, ethoxylated alcohols, and a mixture of heavy aromatic hydrocarbons, e.g. available from Syngenta), as the aqueous diluent, to form an aqueous spray solution which contains a predetermined concentration of the active ingredient (which varies depending on the application rate of the active ingredient to the plants) and 0.5% v/v of the adjuvant Adigor™. This aqueous spray solution is suitable for spraying onto plants.

(203) Seeds of a variety of test species are sown in standard soil in pots. After cultivation for 14 days under controlled conditions in a glasshouse (at 22/16° C., day/night; 16 hours light; 65% humidity), the plants are sprayed post-emergence with the above-mentioned aqueous spray solution containing inter alia the “technical” active ingredient (i.e. the herbicide under test) and the adjuvant Adigor™.

(204) The test plants are then grown on under controlled conditions in the glasshouse (at 22/16° C., day/night; 16 hours light; 65% humidity) and are watered twice daily. 14 days after application of the test herbicide, the test is evaluated visually for percentage phytotoxicity to the plant (where 100%=total damage to plant; 0%=no damage to plant).

(205) More specifically, post-emergence herbicidal activity (phytotoxicity) data, on certain tested grassy monocotyledonous weeds (and/or plants of the type Gramineae) and cereal crops in the glasshouse, are measured 14 days after application of the herbicide (14 DAA), typically for inter alia one or more of the following application rates: (a) a post-emergence application rate of 60 g/ha of the test herbicide with or without 50 g/ha of cloquintocet-mexyl safener, and (b) a post-emergence application rate of 90 g/ha of the test herbicide with 50 g/ha of cloquintocet-mexyl safener, and (c) a post-emergence application rate of 120 g/ha of the test herbicide with 50 g/ha of cloquintocet-mexyl safener.

(206) The cloquintocet-mexyl, when used, is present in the formulation containing the herbicide under test dissolved in acetone plus IF50.

(207) The range of herbicide application rates tested sometimes includes application rates other than those shown above, and the rates can vary depending on the herbicide under test.

(208) Herbicidal activity (phytotoxicity) is 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; the assessment is recorded in increments of 1%). Two replicates are made for each experiment, and the mean herbicidal activity (phytotoxicity) data is reported.

(209) A selection of the results obtained in Biological Example 1B, using substantially the above-described test method, for Compounds A34, A98, A99, A87, A100, A101, A89, A120, A120A, A120B, A23, A127, A128, A89, A112 and A113 are shown below.

(210) For compounds A34, A98, A99, A87, A100, A101, A89, A120, A120A, A120B, A23, A127, A128, A89, A112 and A113 the tested weeds were as follows: Avena fatua (AVEFA), Lolium multiflorum (LOLMU), Setaria viridis (SETVI), Poa annua (POAAN), Alopecurus myosuroides (ALOMY). All five of these are grassy monocotyledonous weeds. Except for SETVI, these are all “cool-season” grassy monocotyledonous weeds.

Biological Example 1B

Post-emergence Herbicidal Activity Against Grassy Weeds—Results (Percentage Phytotoxicity)

(211) Abbreviations: T1=herbicidal test result no. 1, for each of compounds A98 and A99. T2=herbicidal test result no. 2, for each of compounds A98 and A99.

(212) TABLE-US-00018 Herbicide Cloquintocet- Compound application mexyl number Rate application (herbicide) (g/ha) rate (g/ha) AVEFA LOLMU SETVI POAAN ALOMY A34 60 0 100 83 80 78 65 A34 60 50 100 90 85 75 73 A98 60 0 100 (T1)  95 (T1)  94 (T1) 78 (T1) 80 (T1) A98 60 50  100 (T1);   95 (T1);   97 (T1);  75 (T1);  80 (T1); 100 (T2) 100 (T2) 100 (T2) 75 (T2) 78 (T2) A98 90 50 100 (T2) 100 (T2) 100 (T2) 78 (T2) 88 (T2) A98 120 50 100 (T2) 100 (T2) 100 (T2) 83 (T2) 97 (T2) A99 60 0  50 (T1)  35 (T1)  10 (T1) 70 (T1) 50 (T1) A99 60 50   40 (T1);   35 (T1);   8 (T1);  73 (T1);  35 (T1);  48 (T2)  55 (T2)  33 (T2) 70 (T2) 38 (T2) A99 90 50  60 (T2)  65 (T2)  68 (T2) 73 (T2) 58 (T2) A99 120 50  78 (T2)  78 (T2)  75 (T2) 75 (T2) 73 (T2) A87 60 0 100 100 93 83 97 A87 60 50 100 100 95 83 95 A87 30 50 100 100 73 75 70 A100 60 0 100 100 99 80 83 A100 60 50 100 100 99 78 78 A100 45 50 100 100 99 78 75 A100 30 50 100 100 95 73 55 A101 60 0 90 88 53 48 55 A101 60 50 88 83 53 38 55 A101 45 50 88 83 35 15 43 A101 30 50 73 68 15 5 25 A89 60 0 90 100 100 25 98 A89 60 50 90 100 100 15 98 A89 45 50 85 99 100 3 97 A89 30 50 83 90 100 0 88

(213) TABLE-US-00019 Cloquintocet- Compound Herbicide mexyl number application application (herbicide) Rate (g/ha) rate (g/ha) AVEFA LOLMU SETVI POAAN ALOMY A120 60 0 85 100 100 10 85 A120 60 50 78 99 100 3 80 A120 45 50 78 99 100 3 80 A120 30 50 75 98 100 3 75 A120A 60 0 97 100 100 30 95 A120A 60 50 97 100 100 10 90 A120A 45 50 95 100 100 5 88 A120A 30 50 90 97 100 3 80 A120B 60 0 38 83 68 4 73 A120B 60 50 48 73 68 4 70 A120B 45 50 10 73 65 0 58 A120B 30 50 3 58 40 0 43 A23 60 0 80 90 99 0 75 A23 60 50 70 83 99 0 78 A23 30 50 13 48 95 0 28 A127 60 0 85 97 100 0 78 A127 60 50 90 83 100 0 68 A127 45 50 80 83 99 0 63 A127 30 50 55 65 97 0 48 A128 60 0 18 85 55 5 48 A128 60 50 10 78 63 0 35 A128 45 50 3 63 43 0 25 A128 30 50 0 43 23 0 3 A89 60 0 97 100 99 15 99 A89 60 50 93 95 100 3 98 A89 30 50 85 93 95 0 80 A112 60 0 98 100 100 40 99 A112 60 50 97 100 100 13 98 A112 45 50 94 100 100 0 97 A112 30 50 93 98 100 0 97 A113 60 0 5 45 53 8 20 A113 60 50 3 23 55 0 25 A113 45 50 3 20 40 0 18 A113 30 50 1 3 5 0 0

Biological Example 1B

Post-emergence Herbicidal Activity Against Cereal Crops (Wheat and Barley)—Results (Percentage Phytotoxicity)

(214) Abbreviations: T1=herbicidal test result no. 1, for each of compounds A98 and A99. T2=herbicidal test result no. 2, for each of compounds A98 and A99.

(215) TABLE-US-00020 Herbicide Cloquintocet- Compound application mexyl Winter Spring Spring Winter number Rate application Wheat Wheat Barley Barley (herbicide) (g/ha) rate (g/ha) “Hereward” “Teal” “Harrington” “Suzuka” A34 60 0 20 43 83 83 A34 60 50 5 10 33 38 A98 60 0 35 (T1) 30 (T1) 33 (T1) 75 (T1) A98 60 50  13 (T1);  10 (T1);  10 (T1);  13 (T1);  9 (T2)  5 (T2)  4 (T2)  8 (T2) A98 90 50 13 (T2) 13 (T2)  5 (T2)  9 (T2) A98 120 50 23 (T2) 20 (T2) 15 (T2) 40 (T2) A99 60 0  0 (T1)  2 (T1) 15 (T1) 60 (T1) A99 60 50   1 (T1);   1 (T1);   3 (T1);  15 (T1);  0 (T2)  5 (T2)  3 (T2) 14 (T2) A99 90 50  0 (T2)  5 (T2)  5 (T2) 35 (T2) A99 120 50  8 (T2)  8 (T2)  8 (T2) 38 (T2) A87 60 0 43 48 73 83 A87 60 50 33 38 60 60 A87 30 50 23 18 0 3 A100 60 0 60 65 83 93 A100 60 50 40 45 28 53 A100 45 50 30 30 18 30 A100 30 50 15 20 13 10 A101 60 0 43 48 48 75 A101 60 50 38 18 23 40 A101 45 50 23 13 18 23 A101 30 50 18 10 18 23 A89 60 0 60 75 95 95 A89 60 50 28 50 85 73 A89 45 50 25 20 55 20 A89 30 50 15 13 13 8

(216) TABLE-US-00021 Herbicide Cloquintocet- Compound application mexyl Winter Spring Spring Winter number Rate application Wheat Wheat Barley Barley (herbicide) (g/ha) rate (g/ha) “Hereward” “Freya” “Harrington” “Suzuka” A120 60 0 68 55 78 88 A120 60 50 50 30 38 40 A120 45 50 50 30 38 40 A120 30 50 38 18 25 15 A120A 60 0 73 NT 85 93 A120A 60 50 65 NT 73 83 A120A 45 50 60 NT 60 75 A120A 30 50 53 NT 30 23 A120B 60 0 58 NT 53 75 A120B 60 50 13 NT 23 13 A120B 45 50 10 NT 10 9 A120B 30 50 7 NT 3 3 A23 60 0 68 63 75 70 A23 60 50 0 7 5 15 A23 30 50 0 5 1 0 A127 60 0 65 70 83 85 A127 60 50 5 5 8 5 A127 45 50 0 3 0 0 A127 30 50 0 0 0 0 A128 60 0 8 7 48 18 A128 60 50 0 3 0 0 A128 45 50 0 0 0 0 A128 30 50 0 3 0 0 A89 60 0 75 70 88 90 A89 60 50 25 38 43 25 A89 30 50 10 13 13 8 A112 60 0 85 75 93 88 A112 60 50 50 50 73 53 A112 45 50 40 33 45 30 A112 30 50 33 25 30 18 A113 60 0 3 7 33 28 A113 60 50 0 0 8 0 A113 45 50 0 0 0 0 A113 30 50 0 3 0 0 NT = not tested