MXPA00004042A

MXPA00004042A - Substituted benzene compounds, process for their preparation, and herbicidal and defoliant compositions containing them

Info

Publication number: MXPA00004042A
Application number: MXPA/A/2000/004042A
Authority: MX
Inventors: Sandeep Gupta; Masamitsu Tsukamoto; David A Pulman; Baiping Ying; Shaoyong Wu
Original assignee: Isk Americas Incorporated
Priority date: 1997-10-27
Filing date: 2000-04-26
Publication date: 2001-07-09

Abstract

Novel herbicidal and defoliant substituted aniline derived compounds represented by general structure (I) are described. W, X, Y, Z, and Q are as defined in the disclosure. Also described are the processes for the manufacture of these compounds and agriculturally suitable compositions containing these as active ingredients which are useful as herbicides for general or selective pre-emergent or post-emergent control of undesired plant species and defoliants at very low concentrations of these biologically active compounds.

Description

REPLACED BENZENE COMPOUNDS, PROCEDURES FOR YOUR PREPARATION. AND COMPOSITIONS HERBICIDES AND DEFOLIANTES THAT CONTAIN THEM The present invention relates to substituted benzene compounds, to the processes for their preparation, and to the herbicidal and defoliant compositions containing them.

BACKGROUND OF THE INVENTION The use of uracils as herbicides has been previously reported. For example, 3-phenyluracil derivatives are described as herbicides in United States patents 4859229 and 4746352. However, the phenyl ring of the described compounds carries only four substituents. Patent No. 4927451 discloses herbicidal compounds which carry five substituents in the phenyl ring with a dihydrouracil ring. In the EP patent 0705829 uracil herbicides are described which carry a pentasubstituted phenyl ring with a substituent carbon bonded to the 2-position of the phenyl ring. In U.S. Patents 5346881, 5441925, 5169431, 5476834, 5602077, and in WO 97/08170, 08171, 12886 and 42188, uracil herbicides are described which carry a fused pentasubstituted phenyl ring where the 2-position of the ring of phenyl is substituted with either a carbon, an oxygen or a nitrogen. US Pat. Nos. 5116404 and JP 05025144 disclose uracil compounds with a 3-phenyl group which may be pentasubstituted but none of these patents seems to reveal the compounds of the present invention which carry a nitrogen substituent linked. to position 2 of the phenyl ring together with substituents at positions 3,4, and 6 and there appears to be no indication as to the accuracy of the substitution pattern of the phenyl radical in order to introduce a high herbicidal activity in combination with the selectivity towards crops. A similar use of derivatives of pyrazole, tetrahydrophthalimide, triazolinone, tetrazolinone, and triazolidine as herbicides has been described above, for example in U.S. Patents 5281571, 4881967, 5084085, in WO 85/01939, and in Japanese Patent 1-121290 respectively. Pyridazinones, pyridyls, bicyclic hydantoins, phthalimides, pyrimidinones, pyrazinones, and pyridinones as herbicides have also been described, for example in WO 97/07104, 95/02580, 95/23509, in United States Patent 97/06150, 97/06150, 97/11060, and 97/28127. However, despite the broad coverage of these patents, the general structure of the present invention has not been described.

COMPENDIUM OF THE INVENTION This invention describes a method for controlling unwanted vegetation in a crop plant by applying to the growing site an effective amount of a compound described herein. The herbicidal and defoliant compounds of the present invention are described by the following general formula I or its salts: I wherein X is hydrogen, halogen, nitro, amino, NHR, N (R) 2, amide, thioamide, cyano, alkylcarbonyl, alkoxycarbonyl, alkylsulfonamide, unsubstituted or substituted alkyl, haloalkyl, alkoxy, haloalkoxy, alkoxycarbonylalkoxy, benzyloxy, aryloxy, or heteroaryloxy; And it is hydrogen, halogen, or nitro; W is hydrogen, OR, SR, NHR, N (R) 2, CH2R, CH (R) 2, or C (R) 3, halogen, nitro, or cyano, where multiple R groups represent any possible combination of the substituents described by R; R is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, alkoxy, cycloalkyloxy, aryloxy, heteroaryloxy, alkylsulfonyl, benzyl, alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, or heteroaryloxycarbonyl, where any of these groups may be unsubstituted or substituted by any of the functional groups represented by one or more of the following: halogen, cyano, nitro, amino, carboxyl, alkyl, haloalkyl, alkylsilyl, alkylcarbonyl, haloalkylcarbonyl, alkoxy, alkoxycarbonyl, haloalkoxy, haloalkoxycarbonyl, alkylsulfonyl, haloalkylsulfonyl, aryl, heteroaryl, or cycloalkyl; Q is a heterocycle, examples of which are the following: where R is hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, ammonium, alkoxyalkyl, acetyl, alkoxycarbonylamino, alkylcarbonylamino, or alkoxycarbonyl; R2 is alkyl or haloalkyl; RT and R2 could be combined to form a five or six membered heterocyclic ring; R3 is hydrogen, halogen, nitro, amino, alkylamino, haloalkylamino, cyano, or amide; R8 and R9 are independently oxygen, sulfur, or an imino group; Q6, Q7, and Q10 may optionally be unsaturated containing one or two double bonds in the six membered ring; Z is amino, hydroxyl, thiol, formyl, carboxyl, cyano, alkylcarbonyl, arylcarbonyl, azido, or one of the following: where R 4 is alkyl, alkenyl, alkynyl, amino, cycloalkyl, heterocycloalkyl, alkylsulfonyl, arylsulfonyl, benzyl, aryl, heteroaryl, alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, cycloalkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, alkylthiocarbonyl, cycloalkyloxycarbonyl, aryloxycarbonyl, arylthiocarbonyl, arylthiocarbonyl, heteroaryloxycarbonyl, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, heteroarylaminocarbonyl, alkoxycarbonylcarbonyl or arylcarbonylcarbonyl, wherein any of these groups may be unsubstituted or substituted by any one of the functional groups represented by one or more of the following: halogen, cyano, nitro, amino, dialkylamino, hydroxyl, carboxyl, alkyl, alkenyl, alkynyl, cycloalkyl, alkylcarbonyl, alkylcarbonyloxy, alkoxy, alkoxycarbonyl, alkylthio, alkylthiocarbonyl, alkoxythiocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, alkylsulfonyl, alkenyl oxycarbonyl, alkynyloxycarbonyl, aryl, arylcarbonyl, aryloxy, aryloxycarbonyl, arylthio, heteroaryl, heteroaryloxycarbonyl or methylenedioxy, wherein the alkyl radical or the aryl radical can be substituted with halogen, cyano, nitro, alkyl, alkoxy, haloalkyl, haloalkoxy, alkoxycarbonyl, cycloalkyl, aryl, or heterocycloalkyl; and R5 is hydrogen or any of the groups represented by R4; or R4 and R5 could be combined to form a 4- to 8-membered heterocyclic ring; where R6 represents unsubstituted or substituted alkyl, haloalkyl, dialkylamino, and aryl and heteroaryl; and R7 represents hydrogen, halogen or any of the groups represented by R6; -OR4, -SR, -CH2R10, -CH (Ri 0) 2.

-C (R10) 3, or -CH = CHR? Or where R10 is carboxy, alkyl, alkenyl, alkynyl, amino, c-chloroalkyl, heterocycloalkyl, alkylsulfonyl, arylsulfonyl, benzyl, aryl, heteroaryl, alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, cycloalkylcarbonyl , arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, alkyloxycarbonium, cycloalkyloxycarbonyl, aryloxycarbonyl, arylthiocarbonyl, arylthiocarbonyl, heteroaryloxycarbonyl, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, heteroarylaminocarbonyl, alkoxycarbonylcarbonyl or arylcarbonylcarbonyl, wherein any of these groups may be unsubstituted or substituted with any of the functional groups represented by one or more of the following: halogen, cyano, nitro, amino, dialkylamino, hydroxyl, carboxyl, alkyl, alkenyl, alkynyl, cycloalkyl, alkylcarbonyl, alkylcarbonyloxy, alkoxy, alkoxycarbonyl, alkylthio, alkylthiocarbonyl, alkoxythiocarbonyl, alkylaminocarbonyl, arylaminocarbon ilo, alkylsulfonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, aryl, arylcarbonyl, aryloxy, aryloxycarbonyl, arylthio, heteroaryl, heteroaryloxycarbonyl or methylenedioxy, wherein the alkyl radical or the aryl radical may be substituted with halogen, cyano, nitro, alkyl, alkoxy, haloalkyl, haloalkoxy, alkoxycarbonyl, cycloalkyl, aryl, or heterocycloalkyl; provided that (1) Z is not alkyl, alkoxy, haloalkyl, haloalkoxy, alkylthio, haloalkylthio, alkenyl, haloalkenyl, amino, monoalkylamino, dialkylamino, alkoxyalkoxy or cyano, when Q is Q1 and R2 is haloalkyl, (2) Z is not amino when Q is Q3, and (3) Z is not hydroxy, alkoxy, alkenyloxy, alkynyloxy, haloalkoxy, haloalkenyloxy, or -NR4R5, where R is alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl, haloalkenyl, alkylsulfonyl, alkylcarbonyl, alkoxycarbonyl, or cycloalkylalkyl, and R5 is alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl, haloalkenyl, alkylcarbonyl, alkoxycarbonyl, or cycloalkylalkyl, when Q is Q14 or Q15.

DETAILED DESCRIPTION OF THE INVENTION In the above definitions, the term alkyl used either alone or in compound words such as haloalkyl denotes straight or branched chain alkyl containing 1 to 8 carbon atoms. Alkenyl and alkynyl include straight or branched chain alkenes and alkynes containing from 2 to 8 carbon atoms, respectively. The term halogen either alone or in compound words such as haloaiquiio indicates fluorine, chlorine, bromine, or iodine. Additionally a haloalkyl is represented by an alkyl partially or wholly substituted with halogen atoms which may be the same or different. A cycloalkyl group implies a saturated or unsaturated carbocycle containing from 3 to 8 carbon atoms. A heterocycloalkyl group is a cycloalkyl group that carries from 1 to 4 heteroatoms that are represented by oxygen, nitrogen, or sulfur atoms. An aryl group means an aromatic carbocycle containing from 4 to 10 carbon atoms, and may be phenyl or naphthyl. A heteroaryl group is an aromatic ring containing from 1 to 4 heteroatoms represented by oxygen, nitrogen, or sulfur atoms, and may be for example furanyl, pyridyl, thienyl, pyrimidinyl, benzofuranyl, quinolyl, benzothienyl or quinoxalyl. The compound of formula I can form a salt with an acid substance or a basic substance. The salt with an acidic substance can be an inorganic acid salt such as a hydrochloride, a hydrobromide, a phosphate, a sulfate or a nitrate. The salt with a basic substance can be a salt of an inorganic or organic base such as a sodium salt, a potassium salt, a calcium salt, a quaternary ammonium salt such as an ammonium salt or a dimethylamine salt. The compound of formula I can exist in the form of geometric or optical isomers and all these isomeric forms are included in the present invention. Preferred compounds for reasons of ease of synthesis or greater herbicidal efficacy are represented by formula I wherein (1) Z is -NR4R5 or -CH2R10, (2) X is halogen or cyano; And it's halogen; W is -OR; and R is alkyl, alkenyl, or alkynyl, wherein any of these groups may be unsubstituted or substituted with any of the functional groups represented by one or more of the following: halogen, cyano, nitro, amino, or carboxyl, or ( 3) Q is Q1 or Q6; Ri is alkyl, amino or haloalkyl; R2 is haloalkyl; R3 is hydrogen; and R8 and R9 are independently oxygen, sulfur, or an imino group. Compounds represented by formula I where X is halogen are even more preferred compounds for reasons of greater herbicidal efficacy; And it is fluorine; W is OR; R is alkyl, alkenyl, or alkynyl, wherein any of these groups may be unsubstituted or substituted by halogen or cyano; Q is Q1 or Q6; Ri is alkyl, amino or haloalkyl; R2 is haloalkyl; R3 is hydrogen; and R8 and R9 are independently oxygen, sulfur, or an imino group; Z is -NR4R5; R4 is alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, cycloalkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, alkylthiocarbonyl, cycloalkyloxycarbonyl, aryloxycarbonyl, arylthiocarbonyl, arylthiocarbonyl, heteroaryloxycarbonyl, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, heteroarylaminocarbonyl, alcoxicarbonilcarbonilo, arilcarbonilcarbonilo where any of these groups may be unsubstituted or be substituted with any of the functional groups represented by one or more of the following: halogen, cyano, nitro, amino, dialkylamino, hydroxyl, carboxyl, alkyl, alkenyl, alkynyl, cycloalkyl, alkylcarbonyl, alkylcarbonyloxy, alkoxy, alkoxycarbonyl, alkylthio, alkylthiocarbonyl , alkoxythiocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, alkylsuiphenyl, alkenyloxycarbonyl, alkynyloxycarbonyl, aryl, arylcarbonyl, aryloxy, aryloxycarbonyl, arylthio, heteroaryl, heteroaryloxycarbonyl or methylenedioxy, wherein the alkyl radical or the aryl radical may be substituted with halogen, cyano, nitro, alkyl, alkoxy, haloalkyl, haloalkoxy, alkoxycarbonyl, cycloalkyl, aryl, or heterocycloalkyl; and R5 is hydrogen; or Z is -CH2R10; Ro is carboxyl, alkyl, alkenyl, or alkynyl, wherein any of these groups may be unsubstituted or substituted with any of the functional groups represented by one or more of the following: halogen, cyano, nitro, amino, dialkylamino, hydroxyl, carboxyl, alkyl, alkenyl, alkynyl, cycloalkyl, alkylcarbonyl, alkylcarbonyloxy, alkoxy, alkoxycarbonyl, alkylthio, alkylthiocarbonyl, alkoxythiocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, alkylsulfonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, aryl, arylcarbonyl, aryloxy, aryloxycarbonyl, arylthio, heteroaryl, heteroaryloxycarbonyl or methylenedioxy, wherein the alkyl radical or the arylq radical can be substituted by halogen, cyano, nitro, alkyl, alkoxy, haloalkyl, haloalkoxy, akoxycarbonyl, cycloalkyl, aryl, or heterocycloalkyl. Certain intermediates of the present invention are novel. These are 3- (2-amino-4-chloro-6-fluoro-3-methoxyphenyl) -1-metho-6-trifluoromethyl-2,4 (1H, 3H) -pyrimidinedione, the 3- (2- amino-4-chloro-6-fluoro-3-methoxyphenyl) -1-amino-6-trifluoromethyl-2,4 (1H, 3H) -pyrimidinodone and are represented by the following formulas (III-V): where X, Y, W and Q are defined as before; and M is nitro.

IV V where X 'and Y' are halogens; and R is defined as before. The compounds described by the formula I can be prepared by the methods described herein. In general, the compounds described in this invention can be prepared by one of the two routes depending on whether the heterocyclic ring (eg the uracil ring) is formed before or after nitration of the 2-position of the phenyl ring in the product final. As shown in Scheme 1, the starting substances for these preparations are the compounds represented by the formula Vlc. These compounds can be prepared starting from the nitro compound Via via the amine Vlb by the methods described in the literature, for example in the United States patent 4859229 (1989). The nitration of Vlc is typically carried out by its slow addition to a mixture of sulfuric acid and nitric acid in a ratio of 9: 1. Typically 3-4 ml of the nitration mixture is used for 2-3 mmoles of VI and the addition is carried out between 0 and -30 ° C followed by stirring at room temperature for 0.5-2 hours. The product (VII) is separated by adding the solution to ice water and filtering the precipitated product. The product can also be extracted from the aqueous layer in organic solvents such as ether or ethyl acetate and purified by crystallization or column chromatography. The alkylation of VII to VIII can be completed by treating Vil with alkyl halide, haloalkyl halide, especially the respective chloride, bromide, or sulfate in the presence of a base such as potassium carbonate, or sodium hydride in an inert solvent such as acetone, dimethylformamide, dimethisulfoxide, tetrahydrofuran, methyl ethyl ketone, or acetonitrile in a temperature range from 0 to 130 ° C. VIII can be reduced to the amine (IX) under typical reducing conditions such as treatment with iron in acetic acid or ethanolic hydrochloric acid; or by hydrogenation using palladium on carbon or platinum oxide as a catalyst. The product IX is purified by the typical purification procedures of re-crystallization or column chromatography. The amine (IX) can be derivatized to produce a variety of products generally represented by the formula X. For example the amides can be prepared by treatment of IX with halides of alkyl or aryl acids, typically chlorides, or anhydrides in the presence of a base in an inert solvent. Typically, organic bases such as triethylamine, diisopropylethylamine, or pyridine can be used in inert solvents such as tetrahydrofuran, acetonitrile, or dioxane at a temperature range from room temperature to reflux temperature for 2-24 hours. Pyridine can be used alone as a solvent and base. Acylation catalysts such as dimethylaminopyridine (DMAP) can be added to facilitate the reaction. Typical processing methods include solvent removal followed by partitioning the product between aqueous and organic solvents such as ether, ethyl acetate or methylene chloride. Depending on the reactivity of the acid halide, the product typically consists of a monoamide, diamide, or a mixture of the two. These can be purified / resolved typically by column chromatography. The mono- or dialkyl (amino) derivatives of IX can be prepared by their treatment with alkyl halides or haloalkyl in the presence of a base such as sodium or potassium carbonate, or sodium hydride in an inert solvent such as tetrahydrofuran. or dimethylformamide at a temperature from the environment at 120 ° C for 2-24 hours. The mono- or dicarbamoyl derivatives of IX can be prepared by their treatment with alkyl haloformates such as methyl or ethyl chloroformate in the presence of a base such as potassium carbonate or sodium in an inert solvent such as tetrahydrofuran or dimethylformamide at a temperature from the environment at 120 ° C for 2-24 hours. The mono- or diurea derivatives of IX can be prepared by their treatment with an alkyl or aryl isocyanate., for example methyl or ethyl isocyanate, in the presence of a base such as triethylamine in an inert solvent such as toluene or tetrahydrofuran. Alternatively, IX is first converted to its isocyanate derivative by treatment with phosgene or triphosgene in toluene or tetrahydrofuran at the reflux temperature for 2-6 hours. This isocyanate can, in turn, be treated with an alkyl- or arylamine such as methyl- or ethylamine in the presence of a base such as triethylamine in a solvent such as toluene or tetrahydrofuran in a temperature range from the ambient to 130 ° C during 2-12 hours to provide the corresponding urea. IX can be treated with an alkyl dihalide such as 1,4-diiodobutane in an inert solvent such as toluene or acetonitrile at the reflux temperature in the presence of a base such as potassium or sodium carbonate to provide the corresponding cyclized product such as a pyrrolidine derivative. IX can be treated with an aromatic or aliphatic aldehyde or ketone or its diethyl- or dimethylacetal derivative in an inert solvent such as toluene or methylene chloride to provide the corresponding imino derivative. Alternatively, a monoacetylated derivative of IX can be treated with a dehydrochlorination agent such as phosphorus pentachloride to provide the corresponding iminochloride.

SCHEME 1 \ ~ M = N02 Via Vlc a (^ M = NH2 Vlb IX (a) catalytic reduction; (b) triphosgene, 2) NaH, ethyl 3-amino-4,4,4-trifluorocrotonate; (C) H2SO4-HNO3; (d) dimethyl sulfate, base (e) Fe-AcOH; (f) (CF3CO) 2O, (e.g. Z = NHCOCF3). The starting uracil derivative represented by formula XI of Scheme 2 can be prepared according to the procedure described above. Compound XI is nitrated with concentrated nitric acid at 0 ° C at room temperature for 15 ~ 30 minutes. The product (XII) is obtained by adding the product mixture to ice water followed by filtration.

SCHEME 2 The starting uracil derivative represented by the formula XII! of Scheme 3 can be prepared according to the procedure previously described. Compound XIII can be nitrated with nitric acid at 0 ° C for 15 ~ 30 minutes. The product (XIV) is obtained by the addition of ice followed by filtration.

SCHEME 3 XIV XIII The desired starting tetrazole derivatives represented by formula XV of Scheme 4 can be prepared according to the procedure of the WO 85/01939 literature. These compounds can be nitrated with nitric acid at room temperature or at 0 ° C for 15 ~ 30 minutes. The product (XVI) is isolated by the addition of ice followed by extraction in an organic solvent such as ether or ethyl acetate and purified. XVII can be prepared by reducing XVI typically by catalytic hydrogenation in the presence of catalysts such as palladium on carbon or by treatment with iron in acetic acid or in ethanolic hydrochloric acid. XVIII can be prepared by reacting XVII with a halide in the presence of a base of 50 to 120 ° C for 1 - 5 hours. The further modification of XVIII to XIX is carried out according to the general procedures described for the preparation of X from IX (Scheme 1).

SCHEME 4 XVII XV XVI xvtu XIX (a) HNO3; (b) Fe-AcOH; (c) R-X-K2CO3; (d) (CF3CO) 2O, (e.g. Z = NHCOCF3) The starting triazolinone derivative represented by formula XX of Scheme 5 can be prepared according to the process of the literature of United States Patent 4980480 (1990). Compound XX is nitrated with concentrated nitric acid at -15 to 0 ° C for 0.5 ~ 2 hours. The product (XX) is obtained by adding the product mixture to ice water followed by filtration.

SCHEME 5 XX XXI The desired starting pyrazole derivatives represented by formula XXII of Scheme 6 can be prepared according to the method of the literature of United States Patent 5281571 (1994). These compounds can be nitrated in a mixture of sulfuric acid-nitric acid (9: 1) with a proportion of 3-4 ml of the nitrating solution by 3-4 mmole of XXII. The addition is carried out between -15 and -30 ° C followed by stirring at room temperature for 1-2 hours. The product (XXIII) is isolated by the addition of water followed by extraction in an organic solvent such as ether or ethyl acetate and purified. XXIV can be prepared by reduction of XXIII typically by catalytic hydrogenation in the presence of catalysts such as palladium on carbon or by treatment with iron in acetic acid or in ethanolic hydrochloric acid. Additionally the modification of XXIV to XXV is carried out according to the general procedures described for the preparation of X from IX (Scheme I).

SCHEME 6 (a) H2S04-HN03; (b) catalytic reduction; (c) (CF3CO) 2O, (e.g. Z = NHCOCF3) The desired starting tetrahydrophthalimide derivative represented by formula XXVI of Scheme 7 can be prepared according to the procedure of the patent literature of the United States 4484941 (1984). The compound can be nitrated with nitric acid at 0 ° C at room temperature for half an hour. The product (XXVII) is isolated by the addition of ice followed by extraction in an organic solvent such as ether, ethyl acetate, or methylene chloride and purified. XXVIII can be prepared by reducing XXVII typically by catalytic hydrogenation in the presence of catalysts such as palladium on carbon or by treatment with iron in acetic acid or in ethanolic hydrochloric acid. XXIX can be prepared by reacting XXVIII with (substituted) alkyl halide in the presence of a base such as potassium carbonate. The further modification of XXIX to XXX is carried out according to the general procedures described for the preparation of X from IX (Scheme I). (a) HNO3; (b) Fe-AcOH; (c) R-X, K2CO3; (d) (CF3CO) 2O, (V.g. Z = NHCOCF3) Scheme 8 describes the preparation of intermediates represented by formulas XXXIII and IV. The starting substances (derivatives of aminophenols and alkyl represented by the formula Vlb) are prepared according to the process described in the literature such as in the patent of the United States 4670046 (1987) which after treatment with phthalic anhydride in acetic acid can provide the phthalimide derivative (XXXI). The nitration of XXXI can be carried out by adding it to a mixture of sulfuric acid and nitric acid (9: 1) of -15 to -30 ° C followed by the addition of water and the extraction of the product (XXXII) in solvents organic compounds such as ethyl acetate or ether. XXXII can be reduced to the corresponding amine (XXXIII) by conventional methods such as treatment with iron in acetic acid or ethanolic hydrochloric acid or by catalytic hydrogenation in the presence of palladium on carbon. The amino group of XXXIII can be derived as described above in Scheme 1 to provide XXXIV which in turn can be deprotected to provide XXXV. The separation of the protective phthalimide group can be completed by various methods such as treatment with hydrazine in a polar solvent such as dimethyl sulfoxide or by treatment with an organic amine such as methylamine in ethanol. The XXV can be derived to the desired compound (X) according to the known procedures described above in Scheme 1. Alternatively, XXXII can be first subjected to deprotection to provide the amine IV which can be modified to introduce the heterocyclic ring such as the ring of uracil (U in XXXVI) according to known procedures. The nitro group of XXXVI can then be reduced to provide the amine which can then be derivatized as previously described to provide X.

SCHEME 8 (a) AcOH, phthalic anhydride; (b) H2SO4-HNO3; (c) Fe-ACOH; (d) dimethyl sulfate, base, [e.g. Z = N (CH32); (e) DMSO-hydrazine; (f) 1) triphosgene, 2) NaH, ethyl 3-amino-4,4,4-trifluorocrotonate, 3) CH3l (R? = CH3, R2 = CF3); (9) 1) triphosgene, 2) NaH, ethyl 3-amino-4,4,4-trifluorocrotonate, 3) CF3); U = uracil ring as in XIV); (h) 1) Fe-AcOH, 2) (CF 3 CO) 2 O, (e.g. Z = NHCOCF 3). Scheme 9 describes a process for the preparation of intermediates represented by formula V. The starting substances represented by formula XXXIX are prepared by the nitration of XXXVII which gives XXXVIII which can be reduced to XXXIX according to the process of Japanese Patent Literature 01186849 (1989). The amino group of XXXIX is protected by forming the amide or carbamate XL and the latter is nitrated to give XLI. The deprotection of XLI leads to ortho-nitroaniline V. V can be converted into the desired compounds represented by XLV according to the procedures shown in the scheme.

SCHEME 9 XXXVII X JJ == NO2 xxxvm:? NO, XLI ?? = halogens J = NH2 XXXIX c Z ~ J = amide, carbamate XL T = heteroatom XLII R = alkyl, haloalkyl »c XLV (a) H2SO4-HNO3; (b) Fe-AcOH; (c) pyridine-CICOOEt (e.g. J = NHCOOEt); (d) H2SO4-HNO3; (e) HBr-AcOH; (f) 1) triphosgene, 2) NaH, ethyl 3-amino-4,4,4-trifluorocrotonate, 3) CH3I (Q = uracil ring as in X, R, = CH3, R2 = CF3); (g) ROH, base (e.g. T = O, R = CH3); (h) Fe-AcOH, (i) (CF3CO) 2O, (e.g. Z = NHCOCF3). Scheme 10 describes the preparation of the intermediate represented by formulas XLVIII. The starting material (XLVI) can be prepared according to the method described in the patents, for example in United States Patent 5154755 (1992). XLVI is reacted with ethyl chloroformate under alkaline conditions to give the carbamate XLVII. The latter is nitrated with a mixture of nitric acid and sulfuric acid to give the XLVIII intermediate which can be N-alkylated with an alkyl halide in the presence of a base to provide XLIX.

SCHEME 10 XLVI XLVII XUX XLVI? (a) CICOOEt-K2C03; (b) H2SO4-HN03; (c) CH3, -K2CO3. Scheme 11 describes an alternative process for the preparation of the compounds represented by the formula LVII by varying the R groups. The reduction of L to Ll is carried out using conventional procedures such as catalytic reduction or the iron-acetic acid mixture. The aniline Ll is reacted with ethyl chloroformate to provide a carbamate represented by formula Lll which is nitrated with an inorganic salt such as ammonium or potassium nitrate in an acid anhydride such as acetic anhydride according to the published procedure such as described in WO 97/42188. The resulting nitro derivative Lili is cyclized to provide the uracil derivative LIV after reaction with an appropriately substituted aminocrotonate in the presence of an inorganic or organic base exemplified by 1,8-diaza-bicyclo (5.4.0] undec-7-. En (DBU) LIV is derivatized at N to provide LV followed by reduction to LV aniline according to the conventional procedures described above, then LVII is derived to provide the final compounds represented by formula LVIl according to the procedures described above.

SCHEME 11 r = N02 L Lll a ^ = NH2 Ll LIV e • ' f .. RX NiN. *. m LVI LVII (a) catalytic reduction; (b) CICO2C6H5; (c) Ac2O-NH4NO3; (d) ethyl 3-amino-4,4,4-tpfluorocrotonate, DBU, DMF; (e) CH3I; Fe-AcOH (g) (CF 3 CO) 2 O, (e.g. Z = NHCOCF 3). Scheme 12 describes a process for the preparation of compounds represented by the formula LXII which are trisubstituted phenyl derivatives. The ortho-nitroaniline derivatives represented by the formula LVIII are the starting substances that are converted to ortho-nitrouracil (LX) derivatives according to the procedures previously described, e.g. via the NH-uracil derivative (LIX). The nitro groups are then converted to an amino group (LXI) via conventional reduction methods such as reduction with iron-acetic acid followed by derivatization to provide LXI1.

SCHEME 12 LXIl (a) NaH, ethyl 3-amino-4,4,4-trifluorocrotonate; (b) CH3I; (c) Fe-AcOH; (d) (CF3CO) 2, (e.g. Z = NHCOCF3). Scheme 13 describes a process for the preparation of trisubstituted phenyl derivatives represented by the formula LXVI. The direct nitration of LXIII, where X and Q (a heterocycle) are defined as before, using nitration reagents such as nitric acid or a mixture of sulfuric acid-nitric acid leads to ortho-nitro compounds represented by the formula LXIV which are reduced to the corresponding aniline derivatives (LXV) by reduction methods such as catalytic reduction or iron-acetic acid. The aniline (LXV) is then derived to produce LXVI.

SCHEME 13 O) 2O, (eg Scheme 14 defines a process for the preparation of tetrasubstituted phenyl derivatives represented by formula LXXIV.) The process is analogous to that described in scheme 11 for the preparation of pentasubstituted phenyl derivatives (LVII). Nitrate intermediates (LXVIl) are reduced to anilines (LXVIII) via conventional procedures followed by derivatization to the phenyl carbamate (LXIX) by reaction with phenyl haloformate.Nitration to LXX (inorganic nitrate-acid anhydride) is followed by the formation of the uracil ring (appropriately substituted crotonate DBU) (LXXI) and derivation in N to provide LXX1I The reduction to the aniline (LXXIII) is carried out by procedures such as catalytic reduction or iron-acetic acid followed by derivation to provide LXXIV.

SCHEME 14 and ~ M = N02 LXVIl LXIX - = NH2 LXVIII LXXI (a) catalytic reduction; (b) CICO2C6H5; (c) AC2O-NH4NO3; (d) ethyl 3-amino-4,4,4-trifluorocrotonate, DBU, DMF; (e) CH3I; (f) Fe-AcOH (g) (CF3CO) 2O, (.g. Z = NHCOCF3). The scheme 15 describes several procedures for the derivation of the amino group in LXXV via diazonium salts represented by LXXVI. The diazonium salts are prepared by treating the aniline with a solution of inorganic nitrite such as sodium or potassium nitrite in an acid such as sulfuric acid or hydrochloric acid or by treatment of the aniline with an organic nitrite such as nitrite of t- butyl in an organic solvent such as acetonitrile. The reaction is carried out between 10 and -15 ° C which results in a stable solution of the diazonium salt which is reduced to the corresponding hydrazine derivative represented by the formula LXXVII by reducing agents exemplified by stannic chloride. The hydrazine derivatives are then derivatized to a variety of compounds represented by the formula (LXXXVI) via conventional reactions such as acylation, alkylation, formation of the Schiff bases, etc. The diazonium group of LXXVI is replaced by a hydroxyl to provide the corresponding phenol (LXXVIII) by treating it with an aqueous solution of cuprous oxide in the presence of cupric nitrate or cupric sulfate at room temperature. LXXVIII is then derived to provide LXXXVI via conventional reactions such as acylation, killing, etc. The treatment of the diazonium salts (LXXVI) with disulfides (RSSR) leads to the formation of the corresponding thioethers represented by the formula LXXIX which can be further modified according to conventional procedures leading to the sulfur analogs represented by the formula LXXXVI. LXXV1 can be treated with inorganic cyanides leading to the formation of cyanoderivatives (LXXXI) that can be oxidized via conventional routes to provide carboxylic acids (LXXXV) that can then be derived leading to LXXXVI. The diazonium group can also be replaced by an azido group by providing LXXX. LXXVI can be treated with inorganic iodides to provide iodinated compounds (LXXXII) which can be converted to the corresponding aldehydes (LXXXIII) (which are also obtainable directly from LXXVI via conventional methods). LXXXIII can be reduced to provide the corresponding benzylic alcohols (LXXXIV) which can be derivatized to LXXXVI. (a) H2SO4-NaNO2, A = anion; (b) SnCl2; (c) (CF3CO) 2O, (e.g. Z = NHCOCF3); (d) Cu20; (e) C6H5CH2CI (e.g. Z = OCH2C6H5); (f) ethyl acrylate-CuCl2 (e.g. Z = CH2CHCICOOC2H5); (g) RSSR; (h) MCPBA (e.g. Z = SO2R); (i) NaCN; H2SO .; (k) RNH2 (e.g. Z = CONHR); (i) Oxime, CuSO4-Na2SO3; (m) KmnO4; (n) Kl; (o) CO, Pd (II) acetate, triphenylphosphine; (p) NaBH4; (q) e.g. RNCO (Z = CH2OCONHR); (r) NaN3. Scheme 16 describes an alternative process for the formation of amides (XC). The reaction of ortho-aminophenol LXXXVII with an aliphatic or aromatic acyl halide in an organic solvent such as 1,4-dioxane or tetrahydrofuran in the absence or presence of an inorganic or organic base such as potassium carbonate, sodium carbonate, or triethylamine , regioseletivamente leads to the formation of the corresponding amide represented by the formula LXXXIX. LXXXIX can also be produced by hydrolysis of a corresponding alkyl ether such as methyl ether (LXXXVIII) by treatment with strong Lewis acids such as boron tribromide or boron tribromide-dimethyl sulfide complex. The phenol group of LXXXIX is then derivatized by treatment with a halide in the presence of a base such as sodium carbonate or potassium carbonate in an inorganic solvent such as acetone, methyl ethyl ketone, dimethylsulfoxide, or tetrahydrofuran at temperatures from ambient to reflux .

SCHEME 16 (a) Acyl halide; (b) BBr3.Me2S; (c) RiX, base (V.g. R = 2-naphthyl, R1 = CHF2). Scheme 17 describes a process for the preparation of pyridazinone derivatives represented by the formula XCVII and XCVIII. The desired starting pyridazinone derivatives represented by the formula XCI and XCIV can be prepared according to the method of the literature of WO 97/07104. These compounds can be nitrated with nitric acid or a mixture of nitric acid and sulfuric acid at room temperature or at 0 ° C for 15 ~ 30 minutes. The XCII and XCV products are isolated by the addition of ice followed by filtration. XClll and XCVI can be prepared by reduction with iron in acetic acid or in ethanolic hydrochloric acid. The XCIII methylation can be carried out by reacting XCIII with methyl iodide in the presence of a base of 50 to 120 ° C for 1 ~ 5 hours. Further modification of XCVI to XCVIII is carried out by treating the aniline with an organic nitrite (such as t-butyl nitrite) in an organic solvent (such as acetonitrile) and alkyl acrylate in the presence of copper chloride (II). ). The modification of XCVI to XCVII is carried out by treating the aniline with an alkyl or aryl acid halide of 50 to 120 ° C for 1-5 hours.

SCHEME 17 XCVill XCVII (a) HNO3; (b) Fe-AcOH; (c) CH3I, base; (d) H2SO4-HNO3; (e) R2X, base; (f) ethyl t-Buono-acrylate-SITC2.

EXAMPLE 1 Preparation of 3- (4-chloro-6-fluoro-3-methoxy-2-nitrophenyl) -6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (Compound No. 1-1) Was added slowly 3- (4-Chloro-6-fluoro-3-methoxyphenyl) -6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (10.0 g, 29.5 mmol) to a stirred mixture of concentrated sulfuric acid (36 ml) and concentrated nitric acid (4 ml) with stirring at -15 ° C. The solution was then slowly warmed to room temperature and stirred for 2 hours. The addition of the solution to ice water resulted in a pale yellow precipitated product which was filtered off to give the title compound (9.1 g). The NMR data for the compound are listed in Table XVIII.

EXAMPLE 2 Preparation of 3- (4-Chloro-6-fluoro-3-methoxy-2-nitrophenyl) -1-methyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinodone (Compound no. 1-5) was dissolved 3- (4-chloro-6-f luoro-3-methoxy-2-nitrophenyl) -6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (9 g, 23.5 mmoles) in dimethylformamide (90 ml) and to this were added potassium carbonate (3.9 g, 28.2 mmol) and dimethyl sulfate (10.2 g, 47 mmol) with stirring. The solution was stirred at room temperature for 12 hours and water was added. The product was extracted into ethyl acetate and the organic layer was washed with water and dried over anhydrous sodium sulfate. Removal of the solvent gave a crude product which was purified by column chromatography on silica gel. Elution of the column with methylene chloride gave the title compound (7.8 g).

EXAMPLE 3 Preparation of 3- (2-amino-4-chloro-6-fluoro-3-methoxyphenyl) -1-methyl-6-trifluoromethyl-2,4 (1H, 3H) -pyrimidinedione (Compound No. 1-4) It was dissolved 3- (4-chloro-6-fluoro-3-methoxy-2-nitrophenyl) -1-methyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (7.5 g, 18.9 mmoles) in acetic acid (75 ml) and 4.2 g (75.6 mmoles) of iron powder were added. The solution was stirred at room temperature under a nitrogen atmosphere for 6 hours and water was added. The extraction was carried out with ethyl acetate. The organic layer was washed with water, brine, and dried with anhydrous sodium sulfate followed by evaporation to give the title compound (6.8 g).

EXAMPLE 4 Preparation of 3- [4-chloro-2- (2,4-difluorobenzoyl) -amino-6-f luoro-3-methoxy-enyl] -1-methyl-6-trifluoromethyl -2,4 (1H, 3H) -pyridinonenedione (Compound No. 2-42) 3- (2-amino-4-chloro-6-fluoro-3-methoxyphenyl) -1-methoxy-6-trifluoromethyl-2,4 ( 1 H, 3H) -pyrimidinedione (2.0 g, 5.4 mmol) and triethylamine (0.66 g, 6.5 mmol) in anhydrous tetrahydrofuran (30 ml) and stirred under ice-cooling. To this solution was slowly added 2,4-difluorobenzoyl chloride (0.96 g, 5.4 mmol) and the solution was refluxed for 2 hours. Another batch of 2,4-difluorobenzoyl chloride (0.19 g, 1.1 mmol) was added and the solution was refluxed for 2 hours. The solvent was removed in vacuo and the product was purified by column chromatography on silica gel using hexane-ethyl acetate (3: 1) as eluent to give the title compound (2.2 g).

EXAMPLE 5 Preparation of 3- (4-chloro-2-diacetylamino-6-fluoro-3-methoxyphenyl) -1-methyl-6-trifluoromethyl-2,4 (1H, 3H) -pyrimidinedione (Compound No. 2-2) A mixture of 3- (2-amino-4-chloro-6-fluoro-3-methoxyphenyl) -1-methyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (0.5 g, 1, 4 mmol), triethylamine (0.53 g, 5.6 mmol), acetic anhydride (0.57 g, 5.6 mmol), and anhydrous toluene (10 mL) was refluxed for 12 hours. The solvent was removed in vacuo and the product was purified by column chromatography on silica gel. The column was eluted with hexane-ethyl acetate (7: 3) to give the title compound (0.34 g).

EXAMPLE 6 Preparation of 3- (4-chloro-2-dimethylamino-6-fluoro-3-methoxyphenyl) -1-methyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (Compound No. 1-11) ). To a solution of 3- (2-amino-4-chloro-6-fluoro-3-methoxyphenyl) -1-methyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (0.6 g, 1 , 6 mmol) in toluene (10 ml) was added potassium carbonate (0.27 g, 1.92 mmol) followed by dimethyl sulfate (0.69 g, 3.2 mmol). The solution was refluxed for 2 hours and the solvent was removed in vacuo. The residue was chromatographed on silica gel and the product was eluted with methylene chloride to give the title compound (0.12 g).

EXAMPLE 7 Preparation of 3- (4-chloro-6-fluoro-3-methoxy-2-methoxycarbonylaminophenyl) -1-methyl-6-trifluoromethyl-2,4 (1H, 3H) -p-rimidinedione (Compound No. 4) -1) A solution of 3- (2-amino-4-chloro-6-fluoro-3-methoxyphenyl) -1-methyl-l-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione ( 1.25 g) and triethylamine (1 ml) in ethyl acetate (20 ml) was added to a solution of triphosgene (1.0 g) in ethyl acetate (15 ml) stirred under nitrogen. The mixture was refluxed for 2 hours, cooled, filtered and the filtrate was evaporated under reduced pressure to give an ante-colored solid (1.4, g). 1 H NMR (CDCl 3, 300 MHz) 3.58 (3H, s), 4.00 (3H, s), 6.38 (1H, s), 7.12 (1H, d, J = 8.8 Hz) ppm.

The above isocyanate (0.5 g) dissolved in N, N-dimethylformamide (10 ml) was treated with dry methanol (2 ml) and stirred at room temperature for two days. Water and ethyl acetate were added and the solution separated. The organic phase was dried over sodium sulfate, evaporated, and chromatographed on silica gel eluting with ethyl acetate-hexane (1: 3) to give the title compound as a white solid. , 17 g).

EXAMPLE 8 Preparation of 3- [2-bis (methylaminocarbonyl) amino-4-chloro-6-fluoro-3-methoxyphenyl] -1-methyl-6-trifluoromethyl-2,4 (1H, 3H) -pyrimidinodione ( Compound No. 3-1) To a solution of 3- (2-amino-4-chloro-6-f luoro-3-methoxyphenyl) -1-methoxy-6-trifluoromethyl-2,4 (1 H, 3H ) -pyrimidinedione (0.5 g, 1.4 mmol) and triethylamine (0.17 g, 1.7 mmol) in anhydrous toluene (10 ml) was added methyl socianate (0.1 g, 1.7 mmol) ) with agitation. The solution was refluxed for 2 hours and the solvent was removed. The residue was chromatographed on silica gel in methylene chloride-methanol (99: 1) to give the title compound (0.56 g).

EXAMPLE 9 Preparation of 3- [4-chloro-2- (dimethylaminomethyl) -imino-6-fluoro-3-methoxyphenyl] -1-methyl-6-t-rifluoro-methyl-2,4 (1 H, 3H) -pyrimidinedione ( Compound No. 1-31) A mixture of 3- (2-amino-4-chloro-6-fluoro-3-methoxyphenyl) -1-methyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione ( 0.5 g, 1.4 mmol) and dimethylformamide dimethylacetal (0.8 g, 7 mmol) was refluxed for 4 hours under a blanket of nitrogen. The excess reagent was removed in vacuo and the product was extracted with ether. The solvent was removed to provide a residue which was subjected to chromatography on silica gel. Elution of the column with hexane-ethyl acetate (6: 4) provided the title compound (0.22 g).

EXAMPLE 10 Preparation of 3- (2-amino-4-chloro-6-fluoro-3-hydroxyphenyl) -1-methyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (Compound No. 1-16) ) 3- (2-amino-4-chloro-6-fluoro-3-methoxyphenyl) -1-methyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (1.1 g, 2, 7 mmoles) in 50 ml of anhydrous 1,2-dichloroethane and 3.4 g (10.8 mmoles) of boron tribromide-dimethyl sulfide complex were added to the solution. The solution was refluxed for 16 hours and methylene chloride (100 ml) was added. Washing with water followed by drying (anhydrous sodium sulfate) and removal of the solvent gave a residue which was triturated with ether to give the title compound (0.6 g).

EXAMPLE 11 Preparation of 3- (4-chloro-6-fluoro-3-hydroxy-2-nitrophenyl) -6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (Compound No. 1-2) was added - (4-Chloro-2-fluoro-5-hydroxyphenyl) -6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (2.5 g) to concentrated nitric acid cooled with ice (50 ml). After stirring for 1 hour, the reaction mixture was poured into ice-cooled water. The yellow crystals were collected by filtration to provide the title compound (0.9 g). The filtrate was extracted with ethyl acetate (200 ml) and washed with brine. The organic phase was dried over anhydrous sodium sulfate. After removal of the solvent, 0.6 g of the title compound was obtained as a yellow crystal.

EXAMPLE 12 Preparation of 3- (4-chloro-6-fiuoro-3-hydroxy-2-nitrophenyl) -1-methyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (Compound No. 1-17) added 3- (4-chloro-2-fluoro-5-hydroxyphenyl) -1-methyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (1.06 g) to ice-cold concentrated nitric acid ( 10 ml). After stirring for 30 minutes, crushed ice was added. The yellow crystals were collected by filtration to provide the title compound (1.2 g).

EXAMPLE 13 Preparation of 1- (4-chloro-6-fluoro-3-hydroxy-2-nitrophenyl) -4- (3-fluoropropyl) -1,4-dihydro-5-oxo-5H-tetrazole (Compound No. 5) -4) 1 - (4-Chloro-2-fluoro-5-hydroxyphenyl) -4- (3-fluoropropii) -tetrazolinone (2.91 g) was added gradually to ice-cooled nitric acid (20 ml) and stirred for 30 minutes. Crushed ice was added followed by extraction with ethyl acetate. The ethyl acetate extract was washed with water, dried over sodium sulfate, concentrated, and filtered through a gel SPE column, silica (2 g) to give the title compound as a solid. yellow (3.4 g).

EXAMPLE 14 Preparation of 1- (2-amino-4-chloro-6-fluoro-3-hydroxyphenyl) -4- (3-fIuoropropyl) -1,4-dihydro-5-oxo-5H-tetrazole (Compound No. 5) -5) Iron powder (2.3 g) was added to a solution of 1- (4-chloro-6-fluoro-3-hydroxy-2-nitrophenyl) -4- (3-fluoropropyl) -1,4-dihydro-5-oxo -5H-tetrazole (3.4 g) in acetic acid (50 ml) and stirred at room temperature overnight. The reaction mixture was filtered through a pad of celite. The filtrate was concentrated under reduced pressure and purified by a column of silica gel, eluting with hexane-ethyl acetate (2: 1) to give yellow crystals (2.75 g).

EXAMPLE 15 Preparation of 1- (2-amino-4-chloro-6-fluoro-3-propargiloxyphenyl) -4- (3-fluoropropyl) -1,4-dihydro-5-oxo-5H-tetrazole (Compound No. 5) -17) The mixture of 1- (2-amino-4-chloro-6-fluoro-3-hydroxyphenyl) -4- (3-fluoropropyl) -tetrazoline (0.28 g), propargyl bromide (0.13 g) ), and potassium carbonate (0.14 g) in acetonitrile (5 ml) was heated to reflux for 0.5 hour. The solvent and excess reagent were removed under reduced pressure. The residue was purified by a column of silica gel, eluting with ethyl acetate to give the desired product (0.33 g).

EXAMPLE 16 Preparation of 1- (2-amino-4-chloro-6-fluoro-3-isopropyloxyphenyl) -4- (3-fluoropropyl) -1,4-dihydro-5-oxo-5H-tetrazole (Compound No. 5) -18) The mixture of 1- (2-amino-4-chloro-6-fluoro-3-hydroxyphenyl) -4- (3-fluoropropyl) -1,4-dihydro-5-oxo-5H-tetrazole (0, 30 g), isopropyl iodide (1.2 ml), and potassium carbonate (0.14 g) in acetonitrile (5 ml) was heated to reflux for 2 hours. The reaction mixture was evaporated and purified by a column of silica gel, eluting with hexane-ethyl acetate (2: 1) to give the desired product (0.29 g).

EXAMPLE 17 Preparation of 1- (4-chloro-6-fluoro-3-hydroxy-2-nitrophenyl) -4-difluoromethyl-3-methyl-1, 2,4-triazolinone (Compound No. 6-1) was added. - (4-chloro-2-fluoro-5-hydroxyphenyl) -4-difluoromethyl-3-methyl-1, 2,4-triazolinone (0.21 g) to cooled concentrated nitric acid (1.5 ml) at room temperature ambient. The solution was stirred vigorously at room temperature. The solution was stirred vigorously at room temperature for 15 minutes. The reaction mixture was poured into ice water and the yellow precipitated product was collected by filtration to give the title compound (0.17 g) as a 1: 1 mixture with an oxidative compound.

EXAMPLE 18 Preparation of 1- (2-amino-4-chloro-6-fluoro-3-hydroxyphenyl) -4-difluoromethyl-3-methyl-1, 2,4-triazolinone (Compound No. 6-2) To one solution stirring of 1- (1-chloro-6-fluoro-3-hydroxy-2-nitrophenol) -4-difluoromethyl-3-methyl-1, 2,4-triazolinone (0.15 g) in a mixed solvent of hydrochloric acid concentrate (5 ml) and methanol (5 ml) were added 0.3 g of iron powder at room temperature. The resulting mixture was refluxed for 1 hour and the solution was concentrated under reduced pressure. The residue was extracted with ethyl acetate (200 ml) and the organic phase was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give the title compound as a brown oil.

EXAMPLE 19 Preparation of 4-chloro-3- (4-chloro-6-fluoro-3-methoxy-2-nitrophenyl) -1-methyl-5-trifluoromethyl-1 H-pyrazole (Compound No. 7-1) Was discontinued 4-chloro-3- (4-chloro-2-fluoro-5-methoxyphenyl) -1-methyl-5-trifluoromethyl-1 H-pyrazole (1.2 g, 3.5 mmol) with 4 ml of acid concentrated sulfuric acid and added slowly to 4 ml of a stirred mixture of concentrated sulfuric acid-concentrated nitric acid (9: 1) at -15 ° C. The solution was stirred at room temperature for 2 hours and then added to ice water. Extraction with ethyl acetate and removal of the solvent gave a crude product which was subjected to chromatography on silica gel. Elution of the column with hexane-methylene chloride (4: 6) gave the title compound (0.72 g).

EXAMPLE 20 Preparation of 4-chloro-3- (2-amino-4-chloro-6-fluoro-3-methoxyphenyl) -1-methyl-5-trifluoromethyl-1 H-pyrazole (Compound No. 7-2) Was dissolved 4-chloro-3- (4-chloro-6-fluoro-3-methoxy-2-nitrophenyl) -1-methyl-5-trifluoromethyl-1H-pyrazole (, 48 g, 1.24 mmol) in toluene (8 ml) and 0.05 g of 10% palladium on carbon was added. The solution was stirred vigorously under a hydrogen atmosphere for 4 hours at room temperature and the catalyst was removed by filtration. Removal of the solvent gave a residue which was subjected to chromatography on silica gel. Elution of the column with hexane-methylene chloride (3: 7) afforded the title compound (0.38 g).

EXAMPLE 21 Preparation of 6-chloro-4-fluoro-2-nitro-3 (tetrahydrophthalimido) phenol (Compound No. 8-1) 2-Chloro-4-fluoro-5- (tetrahydrophthalimido) phenol (5, 0 g) to nitric acid (50 ml) at 0 ° C, was warmed to room temperature in 30 minutes. Crushed ice was added and the solution was extracted with methylene chloride. The organic phase was washed with water, dried over anhydrous sodium sulfate, and purified by a column of silica gel, eluted with methylene chloride-ethyl acetate (19: 1) to give 3.67 g of the desired product.

EXAMPLE 22 Preparation of 2-amino-6-chloro-4-fluoro-3 (tetrahydrophthalimido) phenol (Compound No. 8-2) Iron powder (2.48 g) was added to a solution of 6-chloro-4- fluoro-2-nitro-3- (tetrahydrophthalimido) phenol (3.67 g) in acetic acid (60 ml) and stirred at room temperature for two hours. The reaction mixture was diluted with ethyl acetate, washed with water, dried over anhydrous sodium sulfate, evaporated to give 3.6 g of the title compound.

EXAMPLE 23 Preparation of N- (2-amino-4-chloro-6-fluoro-3-propargiloxyphenyl) tetrahydrophthalimide (Compound No. 8-3) A mixture of 2-amino-6- was heated at reflux for 0.5 hour. chloro-4-fluoro-3- (tetrahydrophthalimido) phenol (0.31 g), propargyl bromide (0.2 ml), potassium carbonate (0.14 g), and acetonitrile (5 ml). The solvent and excess reagent were removed under reduced pressure. The residue was purified by a column of silica gel, eluting with ethyl acetate to give the title product (0.2 g).

EXAMPLE 24 Preparation of N- (2-amino-4-chloro-6-fluoro-3-isopropyloxyphenyl) tetrahydrophthalimide (Compound No. 8-4) A mixture of 2-amino-6-chloro-2-chloro was heated at reflux for 2 hours. 4-fluoro-3- (tetrahydrophthalimido) phenol (0.31 g), isopropyl iodide (1.2 ml), potassium carbonate (0.14 g), and acetonitrile (5 ml). The solvent and excess reagent were removed under reduced pressure. The residue was purified by a column of silica gel, eluting with ethyl acetate to give the title product (0.21 g).

EXAMPLE 25 Preparation of N- (2-amino-4-chloro-3-cyclopentyloxy-6-fluorophenyl) tetrahydrophthalimide (Compound No. 8-5) A mixture of 2-amino-6-chloro-2-chloro was heated at reflux for 2 hours. 4-fluoro-3- (tetrahydrophthalimido) phenol (0.31 g), cyclopentyl bromide (1.3 ml), potassium carbonate (0.14 g), and acetonitrile (5 ml). The solvent and excess reagent were removed under reduced pressure. The residue was purified by a column of silica gel, eluting with ethyl acetate to give the title product (0.17 g).

EXAMPLE 26 Preparation of 2-chloro-4-fluoro-5- (phthalimido) methoxybenzene. 4-Chloro-2-fluoro-5-methoxyaniline (10.0 g, 57 mmol) and phthalic anhydride (8.5 g, 57 mmol) were dissolved in glacial acetic acid (200 ml) and the solution was refluxed for 2 hours. Water was added and the resulting precipitated product was removed by filtration. The residue was washed with water and dried to give the title compound (16.7 g); 1 H NMR (CDCl 3, 300 MHz) 3.89 (3H, s), 6.9 (1 H, d, J = 6.3 Hz), 7.33 (1 H, d, J = 9.0 Hz), 7 , 82 (2H, m), 7.97 (2H, m) ppm.

EXAMPLE 27 Preparation of 6-chloro-4-fluoro-2-nitro-3 (phthalimido) methoxybenzene 2-Chloro-4-fluoro-5- (phthalimido) methoxybenzene (5.0 g, 16.4 mmol) was added slowly to a stirred mixture of concentrated sulfuric acid-concentrated nitric acid (10: 1, 20 ml) at -20 ° C. The solution was then warmed to room temperature and stirred for 1 hour. The addition of ice water resulted in a light yellow precipitated product which was removed by filtration. Column chromatography on silica gel in hexane-methylene chloride (3: 7) afforded the title compound (3.2 g); 1 H NMR (CDCl 3, 300 MHz) 4.06 (3H, s), 7.54 (1H, d, J = 8.5 Hz), 7.84 (2H, m), 7.97 (2H, m) ppm.

EXAMPLE 28 Preparation of 3-chloro-5-fluoro-2-methoxy-6 (phthalimido) aniline. 6-Chloro-4-fluoro-2-nitro-3- (phthalimido) methoxybenzene (0.5 g, 1.4 mmol) was dissolved in glacial acetic acid (5 ml) and reduced iron (0.32 g, 5.6 mmoles). The solution was stirred at room temperature under a nitrogen stream for 12 hours. Water was added and the product was extracted with ethyl acetate followed by washing with water, brine, and drying (anhydrous sodium sulfate). Removal of the solvent afforded the title compound (0.4 g); 1 H NMR (CDCl 3, 300 MHz) 3.87 (3 H, s), 4.21 (2 H, broad s), 6.65 (1 H, d, J = 9.4 Hz), 7.81 (2 H, m ), 7.95 (2H, m) ppm.

EXAMPLE 29 Preparation of 4-chloro-6-fluoro-3-methoxy-2-nitroaniline. 3-Chloro-5-fluoro-2-methoxy-6- (phthalimido) aniline (0.6 g, 1.7 mmol) was dissolved in dimethyl sulfoxide (3 ml) and anhydrous hydrazine (0.22 g, 6%) was added. 8 mmol). The solution was stirred at room temperature under a nitrogen stream for 12 hours. Water was added and the product was extracted with ether. The organic layer was washed with water, dried (anhydrous sodium sulfate), and evaporated to give the title compound (0.22 g); 1 H NMR (CDCl 3, 300 MHz) 3, 98 (3H, s), 5, 09 (2H, broad s), 7.2 (1H, d, J = 10.5 Hz) ppm.

EXAMPLE 30 Preparation of 4-chloro-6-fluoro-3-methoxy-2-nitrophenyl isocyanate 4-chloro-6-f luoro-3-methoxy-2-nitroaniline (0.5 g, 2.27 g. mmoles) in anhydrous toluene (30 ml) and triethylamine (0.46 g, 4.54 mmol) was added. This solution was added slowly to a stirred solution of triphosgene (0.67 g, 2.27 mmol) in toluene (30 ml) and the solution was refluxed for 2 hours. The solution was cooled and filtered. The clear filtrate was evaporated in vacuo to provide the title compound. 1 H NMR (CDCl 3, 300 MHz) 3.96 (3H, s), 7.38 (1H, d, J = 8.8 Hz) ppm.

EXAMPLE 31 Preparation of 3- [4-chloro-6-fluoro-3-methoxy-2-nitrophenyl] -1-methyl-6-trifluoromethyl-2,4 (1H, 3H) -pyrimidinedione (Compound no. 1-5) from 4-chloro-6-fluoro-3-methoxy-2-nitrophenyl isocyanate.

Sodium hydride (0.06 g, 2.27 mmol) was suspended in 10 ml of anhydrous dimethylformamide and a solution of ethyl 3-amino-4,4,4-trifluorocrotonate (0.42 g, 2 g) was slowly added thereto. , 27 mmol) in anhydrous toluene (10 ml). The solution was stirred for 15 minutes until evolution of hydrogen gas ceased. The solution was cooled to -30 ° C and a solution of 4-cioro-6-fluoro-3-methoxy-2-nitrophenyl isocyanate (2.27 mmol) in anhydrous toluene (10 ml) was slowly added with stirring. The solution was then allowed to warm to room temperature and methyl iodide (1.31 g, 9.1 mmol) was added. After stirring for 4 hours at room temperature, water was added and the product was extracted with ethyl acetate. Column chromatography on silica gel in hexane: methylene chloride (4: 6) gave the title compound (0.13 g).

EXAMPLE 32 Preparation of 2-chloro-4-fluoro-5- (phthalimido) phenol. 5-Amino-2-chloro-4-fluorophenol (3.0 g, 18.6 mmol) and phthalic anhydride (3.3 g, 22.3 mmol) were dissolved in glacial acetic acid (60 ml) and the solution refluxed for 2 hours. Water was added and the resulting precipitated product was removed by filtration. The residue was washed with water and dried to provide the title compound (5.04 g); 1 H NMR (CDCl 3 + CD 3 OD, 300 MHz) 3.68 (1H, s), 6.93 (1H, d, J = 6.6 Hz), 7.27 (1H, d, J = 9.1 Hz) , 7.84 (2H, dd, J = 3.0, 5.5 Hz), 7.97 (2H, dd, J = 3.0, 5.5 Hz) ppm.

EXAMPLE 33 Preparation of 6-chloro-4-fluoro-2-nitro-3 (phthalimido) phenol. 2-Chloro-4-fluoro-5- (phthalimido) phenol (5.0 g, 17.1 mmol) was added slowly with stirring to concentrated nitric acid (50 ml) at -10 ° C. The solution was then warmed to room temperature and stirred for 0.5 hour. Addition of ice water resulted in a light yellow precipitated product that was filtered off to provide the title compound (5.5 g); 1 H NMR (CDCl 3 + CD 3 OD, 300 MHz) 4.36 (1 H, broad s), 7.61 (1 H, d, J = 8.6 Hz), 7.88 (2 H, dd, J = 3.0, 5.5 Hz), 7.99 (2H, dd, J = 3.0, 5.5 Hz) ppm.

EXAMPLE 34 Preparation of 4-chloro-2,5-difluoronitrobenzene (XXXVIII). 1-Chloro-2,5-difluorobenzene (31.7 g, 0.21 mmol) was dissolved in sulfuric acid (110 ml) at -40 ° C, then a solution of sulfuric acid (20 ml) was added dropwise. and nitric acid (30 ml). The mixture was stirred for 1 hour while the temperature was slowly rising to 20 ° C. The product was made to crystallize by mixing the reaction mixture with ice water (500 ml), the crystals were filtered, washed with cold water and dried in a ventilation hood overnight. (38.0 g). 1 H NMR (CDCl 3, 300 MHz) 7.46 (1 H, dd, J = 9, 8, 9, 9 Hz), 7.96 (1 H, dd, J = 7.9, 7.9 Hz) ppm.

EXAMPLE 35 Preparation of 4-chloro-2,5-difluoroaniline (XXXIX). 1-Chloro-2,5-difluoro-4-nitrobenzene (XXXVIII) (17.5 g) in acetic acid (150 ml) was dissolved in a 3-L 3-necked round bottom flask equipped with a condenser condenser. Iron powder (35.0 g) was slowly added thereto while the solution was stirred by an overhead stirrer. The reaction that was exothermic took place in less than 30 minutes and generated a lot of heat that was absorbed by a cooling bath. After that, ethyl acetate (300 ml) was added and the mixture was filtered. The solution was washed with water and dried over sodium sulfate. The product was purified by column chromatography (silica gel, hexane: ethyl acetate, 4: 1) (14.3 g). 1 H NMR (CDCl 3, 300 MHz) 3.89 (2 H, broad), 6.56 (1 H, m), 7.02 (1 H, m) ppm.

EXAMPLE 36 Preparation of ethyl 4-chloro-2,5-difluorophenylcarbamate (XL). 4-Chloro-2,5-difluoroaniline (XXXIX) (2.1 g, 12.8 mmol) was mixed with pyridine (20 ml) at 0 ° C, to which ethyl chloroformate (1.5 g) was added dropwise. g, 13.8 mmol). After stirring for 2.5 hours while the temperature rose slowly to room temperature, the pyridine was evaporated and the residue was crystallized from ice water (100 ml). The crystals were filtered, washed with water and a ventilation hood was dried overnight (2.7 g). 1 H NMR (CDCl 3, 300 MHz) 1.33 (3 H, t, J = 7.1 Hz), 4.23 (2 H, c, J = 7.1 Hz), 3.89 (1 H, broad), 7 , 12 (1H, dd, J = 6.5, 6.5 Hz), 8.05 (1H, dd, J = 7.8, 9.6 Hz) ppm.

EXAMPLE 37 Preparation of ethyl 4-chloro-3,6-difluoro-2-nitrophenylcarbamate (XLI). Ethyl 4-chloro-2,5-difluorophenylcarbamate (XL) (2.4 g, 10.2 mmol) was added to a mixture of sulfuric acid (12.5 ml) and nitric acid (0.8 ml) at - 30 ° C. After stirring for 1.5 hours (-30 ° C to t.a.), it was poured into ice water and dried in a ventilation hood overnight (2.8 g). 1 H NMR (CDCl 3, 300 MHz) 1.30 (3 H, t, J = 7.1 Hz), 4.22 (2 H, c, J = 7.1 Hz), 6.97 (1 H, broad), 7 , 45 (1H, dd, J = 6.3, 6.3 Hz) ppm.

EXAMPLE 38 Preparation of 4-chloro-3,6-difluoro-2-nitroaniline (V). Ethyl 4-chloro-3,6-difluoro-2-nitrophenyl carbamate was mixed (XLI) (0.9 g, 3.2 mmol) with acetic acid (30 ml) and hydrobromic acid (48%, 25 ml), the mixture was stirred at 150 ° C for 4 hours and then the volume was reduced to half by evaporation. Ethyl acetate (50 ml) was added and the solution was washed with water (15 ml x 3) and dried over sodium sulfate. The product was purified by column chromatography (silica gel, hexane) (0.56 g). 1 H NMR (CDCl 3, 300 MHz) 5.73 (2H, broad), 7.24 (1H, dd, J = 6.1, 6.1 Hz) ppm.

EXAMPLE 39 Preparation of 3- (4-chloro-5-ethoxycarbonylamino-2-fluorophenyl) -6-trifluoromethyi-2,4 (1H, 3H) -pyrimidinedione (XLVII). Ethyl chloroformate (2.58 g) was added to a solution of 3- (5-amino-4-chloro-2-fluorophenyl) -6-trifluoromethyl-2,4 (1H, 3H) -pyr? Midinodione ( XLVI) in pyridine (25 ml) at 0 ° C, and stirred at room temperature for one hour. The reaction mixture was diluted with ethyl acetate, washed with 1N hydrochloric acid followed by water, and dried over sodium sulfate. After concentration, the crystals (5.46 g) were collected by filtration. 1 H NMR (CDCl 3, 300 MHz) 1, 31 (3 H, t, J = 7, 1 Hz), 4, 22 (2 H, c, J = 7, 1 Hz), 6.20 (1 H, s), 7 , 14 (1H, broad), 7.29 (1H, d, J = 8.8 Hz), 7.36 (1H, d, J = 6.0 Hz), 8.26 (1H, broad d, J = 6.4 Hz) ppm.

EXAMPLE 40 Preparation of 3- (4-chloro-3-ethoxycarbonylamino-6-fluoro-2-nitrophenyl) -6-trifluoromethyl-2,4 (1H, 3H) -pyrimidinedione (Compound No. 1-33) Was stirred 3- (4-Chloro-S-ethoxycarbonylamino-2-fluorophenyl) -6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (XLVII) (1.0 g) with sulfuric acid (2 ml) at 0 ° C, then a mixture of nitric acid (1 ml) and sulfuric acid (1 ml) was added dropwise. After stirring at room temperature for 3 hours, it was poured into ice water (50 ml) and immediately yellow crystals were formed which were filtered, washed and dried in a ventilation hood overnight (0.5 g).

EXAMPLE 41 Preparation of 3- (4-chloro-3-ethoxycarbonylamino-6-fluoro-2-nitrophenyl) -1-methyl-6-trifluoromethyl-2,4 (1H, 3H) -pyrimidinedione (Compound No. 1-34) 3- (4-Chloro-3-ethoxycarbonylamino-6-fluoro-2-nitro-phenyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (0.96 g) was stirred with dimethyl sulfate (0.72 ml). ) and potassium carbonate (0.33 g) in N, N-dimethylformamide (10 ml) at room temperature overnight The reaction mixture was diluted with ethyl acetate, washed with water, dried over sodium sulfate, sodium, evaporated to give the title compound (1.1 g, oil).

EXAMPLE 42 Preparation of 3- [4-chloro-6-fluoro-3-methyl-2- (naphthoyl) amomofenyl] -1-methyl-6-trifluoromethyl-2,4 (1H, 3H) -pyrimidinedione (Compound no. 2-122) Preparation of 4-chloro-2-fluoro-5-methyl-N-phenoxycarbonylaniline. 4-Chloro-2-fluoro-5-methylaniline (5 g, 31.4 mmol) was dissolved in tetrahydrofuran (100 ml) and potassium carbonate (6.0 g, 37.7 mmol) and phenyl chloroformate were added ( 5.9 g, 37.7 mmol).

The solution was refluxed for 3 hours and the solvent was removed under reduced pressure. The product was purified by column chromatography on silica gel (eluent, methylene chloride: hexane, 6: 4, 7.15 g).

Preparation of 4-chloro-2-fluoro-5-methyl-6-nitro-N-phenoxycarbonylaniline. 4-Chloro-2-fluoro-5-methyl-N-phenoxycarbonylaniline (7.1 g, 25.4 mmol) was dissolved in chloroform (68 ml) and trifluoroacetic anhydride (13.5 g) was added slowly with stirring at room temperature. ml) and ammonium nitrate (2.4 g, 30.5 mmol). Stirring was continued for 18 hours at which time a second batch of ammonium nitrate (0.4 g, 5 mmol) was added and stirring continued for 8 hours. Water was added and the solution was neutralized by the slow addition of a sodium bicarbonate solution followed by extraction with chloroform. The organic layer was dried and evaporated under reduced pressure to provide an oily product (8.5 g) which was used for the next step without purification.

Preparation of 3- (4-chloro-6-fluoro-3-methyl-2-nitrophenyl) -6-tr? Fluoromethyl-2,4 (1H, 3H) -pyrimidinedione. 3-amino-4,4,4-trifluorocrotonate, ethyl (6.1 g, 33.1 mmol) was dissolved in dimethylformamide (47 ml) and stirred at -10 ° C. To this solution was added slowly 1,8-diazabicyclo [5.4.0] undec-7-ene (6.3 g, 41.4 mmol) and the solution was stirred for 0.5 h. To this solution was added slowly a solution of 4-chloro-2-fluoro-5-methyl-6-nitro-N-phenoxycarbonylaniline (8.5 g) in dimethylformamide (25 ml) followed by stirring at room temperature for 14 hours . The solution was then heated to 80 ° C and stirred at this temperature for 4 hours. Water was added and the pH adjusted to 4 by the addition of dilute hydrochloric acid. The product was extracted with ethyl acetate followed by evaporation of the solvent to give the crude product (10.1 g) which was subjected to N-methylation as follows.

Preparation of 3- (4-chloro-6-fluoro-3-methyl-2-nitrophenyl) -1-methyl-6-trifluoromethyl-2,4 (1H, 3H) -pyrimidinedione. 3- (4-Chloro-6-fluoro-3-methyl-2-nitrophenyl) -6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidionendione (10.1 g) was dissolved in dimethylformamide (100 ml. ) and potassium carbonate (5.7 g, 41.3 mmol) and dimethyl sulfate (11.9 g, 55.1 mmol) were added. The solution was stirred at room temperature for 14 hours, water was added and the product was extracted with ethyl acetate. The title compound was separated by column chromatography on silica gel (eluent, hexane-ethyl acetate, 9: 1, 8.5 g).

Preparation of 3- (2-amino-4-chloro-6-fluoro-3-methylphenyl) -1-methyl-6-trifluoro methyl-2,4 (1 H, 3H) -pyr i-midinodione. It was dissolved 3- (4-chloro-6-fluoro-3-methyl-2-nitrophenyl) -1-methyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (2.0 g, 5.2 mmoles) in acetic acid (20 ml) and iron powder (1.2 g, 21.5 mmol) was added. The solution was stirred at room temperature for 14 hours. Water was added and the product was extracted with ethyl acetate followed by evaporation under reduced pressure. The title compound was separated by column chromatography on silica gel (eluent, hexane-ethyl acetate, 7: 3, 1.5 g).

Preparation of 3- [4-chloro-6-fluoro-3-methyl-2- (2-naphthoyl) amomofenyl] -1-methyl-6-trifluoromethyl-2,4 (1H, 3H) -pyrimidinedione. It was dissolved 3- (2-amino-4-chloro-6-fluoro-3-methylphenyl) -1-methyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (0.5 g, 1.4 mmoles) in 1,4-dioxane (20 ml) and triethylamine (0.29 g, 2.9 mmol) and 2-naphthoyl chloride (0.41 g, 2.2 mmol) were added. The solution was heated to reflux for 4 hours and the solvent was removed under reduced pressure. The product was subjected to column chromatography on silica gel and the title compound was eluted with hexane: ethyl acetate (8: 2, 0.3 g).

EXAMPLE 43 Preparation of N- [4-chloro-6-fluoro-3-methoxy-2 (naphthoyl) aminophenyl-phthalimide (Compound No. 13-3) 3-chloro-5-fluoro-2-methoxy-6 (phthalimido) was dissolved aniline (0.32 g, 1 mmol), 2-naphthoyl chloride (0.23 g, 1.2 mmol), and triethylamine (0.12 g, 1.2 mmol) in tetrahydrofuran (20 ml) and the solution it was refluxed for 3 hours. Then the solvent was removed under reduced pressure and the residue was subjected to column chromatography on silica gel. The title compound was eluted with hexane-ethyl acetate (7: 3, 0.12 g).

EXAMPLE 44 Preparation of 3- (2-amino-4-chloro-3-difluoromethoxy-6-fluorophenyl) -1-methyl-6-trifluoromethyl-2,4 (1H, 3H) -pyrimidinedione (Compound No. 1-38) . 3- (2-amino-4-chloro-6-fluoro-3-hydroxyphenyl) -1-methyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinodone (1.41 g) was suspended. 4.0 mmol) and potassium carbonate (0.69 g, 5.0 mmol) in dimethylformamide (50 ml) and stirred at 90 ° C. Chlorodifluoromethane was bubbled through the solution for 4 hours and water was added. The product was extracted with ethyl acetate and subjected to column chromatography (silica gel; eluent, methylene chloride-methanol, 99.5: 0.5) to give the title compound (0.78 g).

EXAMPLE 45 Preparation of 3- [4-chloro-6-fluoro-3-metii-2- (phenoxycarbonyl-amino) fe ni] -1-methyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione ( Compound No. 4-52). 3- (4-Chloro-6-fluoro-2-isocyanato-3-methylphenyl) -1-methyl-6-trifluoromethyl-2,4 (1H, 3H) -pyrimidinedione. 3- (2-amino-4-chloro-6-fluoro-3-methylphenyl) -1-methyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (1.0 g, 2.9 g) was dissolved. mmoles) and triethylamine (0.58 g, 5.7 mmol) in ethyl acetate (15 mL) and the solution was added slowly to a solution of triphosgene (0.85 g, 2.9 mmol) in ethyl acetate ( 15 ml). The solution was refluxed for 2 hours and filtered. The solvent was evaporated to give the title compound as a residue which was used in the next step. 3- (4-Chloro-6-fluoro-3-methyl-2-phenoxycarbonyl-aminophenyl) -1-methyl-6-trifluoridemethyl-2,4 (1 H, 3H) -pyrimidinedione. 3- (4-Chloro-6-fluoro-2-isocyanato-3-methylphenyl) -1-methyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (1.4 mmol) and triet? Laminate (0.14 g, 1.4 mmol) in toluene (15 ml) and the solution treated with phenol (0.13 g, 1.4 mmol). The solution was stirred for 0.3 hours at room temperature and water was added. The product was extracted with ethyl acetate. Removal of the solvent followed by column chromatography on silica gel (eluent, methylene chloride) gave the title compound (0.3 g).

EXAMPLE 46 Preparation of 3- [4-chloro-6-fluoro-3-hydroxy-2- (2-naphthoylamino) phenyl] -1-methyl-6-trifluoromethyl-2,4 (1H, 3H) -pyrimidinedione (Compound no. 2-114). 3- (2-amino-4-chloro-6-fluoro-3-hydroxyphenyl) -1-methyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (0.50 g, 1.4 mmoles) and 2-naphthoyl chloride (0.27 g, 1.4 mmol) in 1,4 dioxane (10 ml) and the solution was heated to reflux for 4 hours. The solvent was evaporated under reduced pressure and the product was purified by column chromatography on silica gel (eluent, hexane-ethyl acetate, 8: 2) to give the title compound (0.60 g).

EXAMPLE 47 Preparation of 3- [4-chloro-3-difluoromethoxy-6-fluoro-2- (2-naphthoylamino) phenyl] -1-methyl-6-trifluoromethyl-24 (1H, 3H) -pyrimidinedione (Compound No. 2-115). 3- [4-Chloro-6-fluoro-3-hydroxy-2- (2-naphthylamino) phenyl] - 1 -methyl I-6-trifluoro methyl-2,4 (1 H, 3H) - pyrimidinedione (0.51 g, 1.0 mmol) dissolved in dimethylformamide (5 ml) to a stirred suspension of sodium hydride (0.03 g, 1.3 mmol) in dimethylformamide (5 ml) at -10 ° C. Chlorodifluoromethane was bubbled through the solution for 0.5 hour with stirring at -10 ° C followed by the addition of water. The product was extracted with ethyl acetate and the solvent was evaporated under reduced pressure. The residue was subjected to column chromatography on silica gel (eluent, hexane-ether, 25:75) to give the title compound (0.03 g).

EXAMPLE 48 Preparation of 3- [4-chloro-2- (2-naphthoylamino) phenyl] -1-methyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (Compound No. 2-131).

To a solution of triphosgene in anhydrous ethyl acetate (150 ml) was added dropwise a solution of 4-chloro-2-nitroaniline (10 g) and triethylamine (12 g) in anhydrous ethyl acetate (50 ml) at 0 ° C. ° C in nitrogen atmosphere. After the addition, the resulting mixture was heated to reflux temperature for 1 hour, then allowed to cool to room temperature. The precipitated product was separated by filtration through Celite and the filtrate was concentrated to give the title compound as a brown solid. To a suspension of sodium hydride (60% dispersion in mineral oil, 2.5 g) in anhydrous N, N-dimethylformamide (100 ml) was added dropwise a solution of 3-amino-4,4,4- Ethyl tpfluorocrotonate in toluene (50 ml) at 0 ° C under nitrogen. After the addition, the mixture was stirred for 20 minutes at the same temperature, then cooled to -30 ° C. A solution of (4-chloro-2-nitrophenyl) isocyanate in toluene (50 ml) was added dropwise. After stirring for 20 minutes, the cooling bath was removed and the resulting mixture was stirred overnight at room temperature. The reaction mixture was partitioned between ethyl acetate and 1N hydrochloric acid. The organic phase was washed with brine (x2) and dried over anhydrous sodium sulfate. The solvent was removed in vacuo and the residue was purified by column chromatography on silica gel eluting with ethyl acetate and hexane (1: 1) to provide 3- (4-chloro-2-nitrophenyl) -6-trifluoromethyl-2 , 4 (1H, 3H) -pyrimidinedione (10.2 g) as a yellow solid.

Preparation of 3- (4-chloro-2-nitrophenyl) -1-methyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione. A mixture of 3- (4-chloro-2-nitrophenyl) -6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (3 g), dimethyl sulfate (1.7 g) and potassium carbonate (1 , 85 g) in N, N-dimethylformamide (100 ml) was stirred at 55 ° C overnight. The resulting mixture was allowed to cool to room temperature and filtered through Celite to remove the insoluble precipitate. The filtrate was diluted with a solvent mixture of ethyl acetate and hexane (1: 1, 200 ml), washed with brine (x2) and dried over anhydrous sodium sulfate. After removal of the solvent, the residue solidified. The yellow solid was recrystallized from ethyl acetate to give the desired compound (2.3 g).

Preparation of 3- (2-amino-4-chlorophenyl) -1-methyl-6-tri-fluoro-methyl-2,4 (1 H, 3H) -pyrimidinedione. To a stirred suspension of 3- (4-chloro-2-nitrophenyl) -1-methyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (1 g) in methanol (20 ml) and hydrochloric acid ( 10 ml) iron (pulverized, 0.48 g) was added with vigorous stirring. After the addition, the mixture was heated to reflux temperature for 1 hour. The oil bath was separated and the solution was allowed to cool to room temperature. Ethyl acetate (200 ml) was added, washed with brine (x2) and dried over anhydrous sodium sulfate. After removal of the solvent, the residue was purified by column chromatography on silica gel using ethyl acetate-hexane (1: 3) as eluent to give the title compound.

Preparation of 3- [4-chloro-2- (naphthoylamino) phenyl-1-methyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (Compound No. 2-131). A solution of 3- (2-amino-4-chlorophenyl) -1-methyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (0.4 g), 2-naphthoyl chloride (0.29 g) and triethylamine (0.19 g) in anhydrous tetrahydrofuran (30 ml) was heated at reflux temperature overnight under nitrogen. The reaction mixture was diluted with ethyl acetate (200 ml), washed with brine (x2) and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel using ethyl acetate and hexane (1: 3) as eluent to give a light yellow solid. The solid was recrystallized from ethyl acetate-hexane to give the title compound as a white crystal (0.42 g).

EXAMPLE 49 Preparation of 3- [4-chloro-6-fluoro-2- (2-naphthoylamino) phenyl] -1-methyl-6-trifluoro methyl-2,4 (1 H, 3H) -pyrimidinedione (Compound No. 2) -145). A mixture of (2-amino-4-chloro-6-fluorophenyl) -1-methyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (0.25 g), triethylamine (0.15 g) and 2-naphthoyl chloride (0.21 g) in anhydrous tetrahydrofuran (30 ml) was heated at reflux temperature overnight under nitrogen. The mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium acetate. The solvent was removed in vacuo and the residue was purified by column chromatography on silica gel using ethyl acetate-hexane (1: 4) as eluent to give the title compound as a white solid (0.26). g).

EXAMPLE 50 Preparation of N- [4-chloro-2- (2-naphthoylamino) phenyl] phthalimide (Compound No. 13-5). A reaction solution of N- (2-amino-4-chlorophenyl) phthalimide (0.5 g), triethylamine (0.28 g) and 2-naphthoyl chloride (0.35 g) in anhydrous tetrahydrofuran (50 ml) it was heated at reflux temperature for 6 hours under a nitrogen atmosphere. The resulting mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with brine (x2) and dried over anhydrous sodium sulfate. The solvent was removed and the residue was purified by column chromatography on silica gel using ethyl acetate-hexane (1: 5) to give the title compound (0.35 g) as a yellow solid.

EXAMPLE 51 Preparation of 3- (2-benzylthioacetylamino-4-chloro-6-f luoro-3-methoxyphenyl) -1-methyl-6-trifluoromethyl-2,4 (1H, 3H) -pyrimidinedione.

(Compound No. 2-165). A solution of benzylmercaptan (51.0 mg) in tetrahydrofuran (1.0 ml) was added slowly to a suspension of sodium hydride (16.4 mg) in tetrahydrofuran stirred under nitrogen at 0 ° C. The solution was warmed to room temperature over 20 minutes and tetrabutylammonium bromide (11 mg) was added. The suspension was cooled to -78 ° C and a solution of 3 (2-chloroacetylamino-4-chloro-6-fluoro-3-methoxyphenyl) -1-methyl-6-trifluoromethyl-2,4 (1 H) was added. , 3H) -pyrimidinedione (150 mg). After stirring for a further 30 minutes, the mixture was allowed to warm to room temperature overnight. Water and ethyl acetate were added and the solution was separated and the organic phase was washed with water, brine and dried over sodium sulfate. The solution was concentrated and chromatographed on silica gel eluting with methylene chloride: ethyl acetate, 10: 1, to give a white solid (137 mg).

EXAMPLE 52 Preparation of 3 -, (2-aminocarbonylamino-4-chloro-6-fluoro-3-methoxyphenyl) -1-methyl-6-trifluo-methyl-2, 4 (1H, 3H) -pyrimidinodone (Compound No. 3-26). An isocyanate solution (1 mM) in dioxane (20 ml), stirred at 0 ° C, was treated with a solution of 0.5 M ammonia in dioxane (3 mM) and 1,8-diazabicyclo [5.4.0 ] undec-7-ene (DBU) (3 drops). The solution was allowed to warm to room temperature and was stirred overnight. Chromatography on silica gel eluting with ethyl acetate gave the product as a yellow solid (271 mg).

EXAMPLE 53 Preparation of 3- (4-chloro-6-fluoro-3-methoxy-2-thiomethylphenyl) -1-methyl-6-trifluoro methyl-2,4 (1 H, 3H) -pyrimidinedione (Compound No. 17- 1). A solution of t-butyl ion (73 mg) in methylene chloride (1 ml) was added to a stirred solution, cooled with ice of 3- (2-amino-4-chloro-6-fluoro) -3-methoxy fe nyl) -1-methyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (200 mg) and dimethyl sulfide (102 mg) in dry methylene chloride (4 ml). This was stirred at 0 ° C for 1.5 hours and allowed to warm to room temperature overnight. 1N hydrochloric acid was added and the mixture was extracted with ethyl acetate, washed with water, brine and dried over sodium sulfate. The solution was concentrated under reduced pressure and the residue was chromatographed on silica gel eluting with ethyl acetate: hexane, 5: 1 to give the product as a yellow powder (189 mg).

EXAMPLE 54 Preparation of 2- (4-chloro-6-fluoro-3-hydroxy-2-nitrophenyl) -5-trifluoromethyl-pyridazin-3-one (Compound No. 11-2). Nitric acid (70%, 12 mL) was added to ice-cold 2- (4-chloro-2-fluoro-5-hydroxyphenyl) -5-trifluoromethyl-pyridazin-3-one (1.25 g) and stirred at room temperature. environment for 30 minutes. Crushed ice was added. The precipitated product was collected by filtration and washed with water to give 1.20 g of the desired product, m.p. 146-8 ° C.

EXAMPLE 55 Preparation of 2- (2-amino-4-chloro-6-fluoro-3-hydroxyphenyl) -5-trifluoromethyl-pyridazin-3-one (Compound No. 11-3). To a stirred solution of 2- (4-chloro-6-fluoro-3-hydroxy-2-nitrophenyl) -5-trifluoromethyl-pyridazin-3-one (0.601 g) in acetic acid (6 ml) was added 0.38 g of Iron powder at room temperature and stirred for 4 hours. The reaction mixture was partitioned between ethyl acetate and water. The organic phase was dried over anhydrous sodium sulfate. After removing the solvent under reduced pressure, the residue was purified by column chromatography on silica gel, eluting with hexane-ethyl acetate (2: 1) to give 0.515 g of the title compound.

EXAMPLE 56 Preparation of 2- (2-amino-4-chloro-6-fluoro-3-methoxyphenyl) -5-trifluoromethyl-pyridazin-3-one (Compound No. 11-4) (BY715) and 2- (4-chloro- 6-fluoro-3-methoxy-2-methylaminophenyl) -5-tri-fluoro-methylpyridazin-3-one (Compound No. 11-5). 2- (2-Amino-4-chloro-6-fluoro-3-methoxyphenyl) -5-trifluoromethyl-pyridazin-3-one (0.515 g), methyl iodide (0.248 g), and potassium carbonate (0.219 g) were mixed. in acetonitrile (10 ml) and heated to reflux for 2 hours. The reaction mixture was partitioned between ethyl acetate and water. The organic phase was dried over anhydrous sodium sulfate. After removing the solvent under reduced pressure, the residue was purified by column chromatography on silica gel, eluting with hexane-ethyl acetate (4: 1) to give 0.40 g of 2- (2-amino-4-chloro) -6-fluoro-3-methoxyphenyl) -5-trifluoromethyl-pyridazin-3-one (Compound No. 11-4) mp 156-7 ° C and 2 (4-chloro-6-fluoro-3-methoxy-2-methylaminophenyl) -5-trifluoromethyl-pyridazin-3-one (Compound No. 11 -5) (7 mg).

EXAMPLE 57 Preparation of 2- (4-chloro-6-fluoro-3-methoxy-2-naphtholamidophenol) -5-trifluoromethyl-pyridazin-3-one (Compound No. 11-6). 2- (2-Amino-4-chloro-6-fluoro-3-methoxyphenyl) -5-trifluoromethyl-pyridazin-3-one (0.153 g) and naphthoyl chloride (0.097 g) were mixed in dioxane (10 ml) and they were heated at reflux for 5 hours. The reaction mixture was partitioned between ethyl acetate and water. The organic phase was dried over sodium sulfate. After removing the solvent under reduced pressure, the residue was purified by column chromatography on silica gel, eluting with hexane-ethyl acetate (4: 1) to give 0.198 g of the title compound, m.p. 190-2 ° C.

EXAMPLE 58 Preparation of 2- (2,4-dichloro-6-fluoro-3-methoxyphenyl!) - 5-trifluoromethyl-pyridazin-3-one (Compound No. 11-7) and 2- [4-chloro-2- ( 2-Chloro-2-ethoxycarbonylethyl) -6-fluoro-3-methoxyphenyl] -5-trifluoromethyl-pyridazin-3-one (Compound No. 11-8). Copper (II) chloride (0.119 g), t-butyl nitrite (0.115 g), and ethyl acrylate (3 ml) were placed in a flask and cooled with a dry ice-acetone bath at -65 ° C. C. To this mixture was added 2- (2-amino-4-chloro-6-fluoro-3-methoxyphenyl) -5-trifluoromethylpyridazin-3-one (0.25 g) in acetonitrile (4 ml) and stirred. The reaction mixture was gradually warmed to room temperature throughout the night. The reaction mixture was partitioned between ethyl acetate and water. The organic phase was dried over anhydrous sodium sulfate. After removal of the solvent under reduced pressure, the residue was purified by column chromatography on silica gel, eluting with hexane-ethyl acetate (9: 1) to give 0.077 g of 2- (2,4-dichloro-6) fluoro-3-methoxyphenyl) -5-trifluoromethylpyridazin-3-one and 0.033 g of 2- [4-chloro-2 (2-chloro-2-ethoxycarbonylethyl) -6-fluoro-3-methoxyphenyl] -5-trifluoromethylpyridazin-3 -one EXAMPLE 59 Preparation of 2- (4-chloro-6-fluoro-3-hydroxy-2-naphtholamidophenyl) -1-methyl-6-trifluoromethyl-24 (1H, 3H) -pyrimidinedione (Compound No. 2-194). Complex of boron tribromide-methyl sulfide (5.15 g) was added to a solution of 2- (4-chloro-6-fluoro-3-methoxy-2-naphtholamidophenyl) -1-methyl-6-trifluoromethyl-2 , 4 (1H, 3H) -pyrimidinedione in 1,2-dichloroethane (150 ml) and heated to reflux for 1 hour. The reaction mixture was partitioned between methylene chloride and water. The organic phase was dried over anhydrous sodium sulfate. After removal of the solvent under reduced pressure, the residue was purified by column chromatography on silica gel, eluting with hexane-ethyl acetate (4: 1 and 2: 1) to give the title compound (4.127 g), m.p. 150-2 ° C.

EXAMPLE 60 Preparation of 2- (4-chloro-3-ethoxy-6-fluoro-2-naphthoylamidophenyl) -6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (Compound No. 2-196). 2- (4-Chloro-6-fluoro-3-hydroxy-2-naphtholamide-phenyl) -1-methyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (0.203 g), ethyl iodide ( 75 mg) and potassium carbonate (55 mg) in methyl ethyl ketone (9 ml) and dimethyl sulfoxide (1 ml) at room temperature over night. The reaction mixture was filtered and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with hexane-ethyl acetate (4: 1) to give the title compound (0.16 g).

EXAMPLE 61 Preparation of 2- [4-chloro-2-diazanyl-6-fluoro-3-methoxyphenyl] -1-methyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (Compound no. -1). It was dissolved 3- (2-amino-4-chloro-6-fluoro-3-methoxyphenyl) -1-methyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (0.9 g, 2.4 mmoles) in concentrated hydrochloric acid (5 ml) and the mixture was cooled to -15 ° C, a solution of NaNO2 (0.2 g in 2 ml of H2O) was added slowly. after stirring for 20 minutes, a solution of SnCl2"2H2O (1.5 g in 4 ml of concentrated hydrochloric acid) was added and the reaction was continued at -15 ° C for 30 minutes. The aqueous mixture was extracted with ethyl acetate (5 ml x 3) and the organic phase was washed with brine and dried over Na 2 SO 4. Column chromatography was used to purify the product (silica gel, hexane / ethyl acetate = 6/4). Yield: 0.5 g, 1.3 mmol.

EXAMPLE 62 Preparation of 2- [4-chloro-2- (2-cyclopropanecarbonyldiazanyl) -6-f-U-3-methoxy-enyl] -1-methyl-6-trif-1-uoromethyl 1-2.4 (1H, 3H) -pyrimidinedione (Compound No. 15-2). It was dissolved 2- [4-chloro-2-diazanyl-6-fluoro-3-methoxyphenyl] -1-methyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (0.15 g, 0.4 mmoles) in dioxane (10 ml) and added to cyclopropanecarbonyl chloride (0.04 g, 0.4 mmol) and triethylamine (0.04 g, 0.4 mmol). After stirring for one hour, the mixture was poured into water (15 ml) and extracted with ethyl acetate (10 ml x 3). The organic phase was washed with brine and dried over Na2SO4. The final purification involved column chromatography (silica gel, ether). Yield: 0.15 g, 0.34 mmol.

EXAMPLE 63 Preparation of 3-. { 4-chloro-2- [2,2- (cyclopropane-methylene) diazanyl] -6-fluoro-3-methoxyphenyl} -1-methyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (Compound No. 15-11). 3- [4-Chloro-2-diazanyl-6-fluoro-3-methoxyphenyl] -1-methyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (0.12 g, 0.31) was added mmoles) was added to a methanol solution (10 ml) of cyclopropanecarboxaldehyde (0.024 g, 0.34 mmol) and the mixture was stirred for 3 hours. After evaporation of the solvent, the residue was purified by column chromatography (silica gel, hexane / ether-3/2). Yield: 0.13 g, 0.31 mmol.

EXAMPLE 64 P • rreeppa; -ration d -e- 3 - • (.4-chloro -6 -fluoro-2-hydroxy-3-methoxyphenyl) -1. methyl-6-trifluoromethyl-2,4 (1H, 3H) -pyrimidinedione (Compound No. 16-6). A solution in acetonitrile (10 ml) of copper (II) sulphate (0.52 g, 3.26 mmol), copper oxide (1) (0.47 g, 3.26 mmol) and copper nitrate (II) ) hemipentahydrate (0.76 g, 3.26 mmol) was stirred at -30 ° C, and t-butyl nitrite (0.41 g, 3.97 mmole) was added and then a solution in acetonitrile (3 ml) of 3- (2-amino-4-chloro-6-f luo ro-3-methoxyphenyl) -1 -met i I -6-trifluo romet 1-2.4 (1 H, 3H) -pyr? midinodione (0.94 g, 2.56 mmol). After stirring for 16 hours (-30 ° C at room temperature), the mixture was poured into cold 5% hydrochloric acid (30 ml) and then extracted with ethyl acetate (20 ml x 3). The organic phase was washed with brine and dried over Na2SO4. Preparative TLC was used for the purification (silica gel plates, 2,000 microns, ether). Yield: 0.16 g, 0.44 mmol.

EXAMPLE 65 Preparation of 3- [4-chloro-6-fluoro-3-methoxy-2- (2-naphthoxy) phenyl] -1-methyl-6-trifluoromethyl-2,4 (1H, 3H) -pyrimidinedione (Compound no. 16-7). It was dissolved 3- (4-chloro-6-fluoro-2-hydroxy-3-methoxyphenyl) -1-methyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (0.10 g, 0.27 mmoles) in dioxane (10 ml) and the solution was added to 2-naphthoyl chloride (0.062 g, 0.33 mmole), triethylamine (0.033 g, 0.33 mmole). After stirring for 2 hours, the solvent was evaporated and the residue was purified by column chromatography (silica gel, hexane / ether = 4/1). Yield: 0.12 g, 0.23 mmol.

EXAMPLE 66 Preparation of 3-. { 4-chloro-2- [2-chloro-2- (ethoxycarbonyl) etl) -6-fluoro-3-methoxyphenyl} -1-methyl-6-trifluoromethyl-2,4 (1 H, 3H) -pyrimidinedione (Compounds Nos. 14-4 and 14-5). A solution of 3- (2-amino-4-chloro-6-fluoro-3-methoxyphenyl) -1-methyl-6-trifluoromethyl-2,4 (1H, 3H) -pyrimidinedione (0.94 g, , 56 mmol) in acetonitrile (3 ml) was slowly added to a solution in acetonitrile (9 ml) of ethyl acrylate (6 ml), t-butyl nitrite (0.41 g, 3.97 mmol), and chloride copper (11) (0.42 g, 3.12 mmol) at -20 ° C. After stirring for 16 hours (-20 ° C at room temperature), the mixture was poured into cold 5% hydrochloric acid (30 ml) and extracted with ethyl acetate (20 ml x 3), the organic phase was washed with 5% NaHCO3 and brine, dried over Na2SO4. For purification, column chromatography (silica gel, hexane / ether = 9/1) was used which also isolated two isomers. Yield: isomer 1 (eiuye first), 0.23 g, 0.47 mmol; isomer 2 (elutes later), 0.14 g, 0.29 mmol. Using the procedures described in Schemes 1-17 and Examples 1-66, the compounds of this invention can be prepared easily. The structures of some representative compounds of this invention are listed in Tables I-XVII.

D? 00 15 twenty O l Ui TABLE II 00 s.

Ul O Ul co Ul or Ui Ul 00 00 Ul O Ui Ui 00 co t Ul Ui Ui CD O to Ul to O Ui Ui CD to Ul O Ul CD t Ul to or Ul Ui 00 to Ul O Ul CD to Ul to or Ul t to Ul or Ul CD O. to Ul to O CD -vi to to Ul or to Ul O Ul Ul TABLE III o o to t Ul O Ui to O Ui Ul TABLS IV or what ? o t Ul or Ul oJ to t Ul or Ul Ul o to IO Ul or Ul Ui or Ol ? o to Ul O Ul or fj) TABLE V TABLE VI TABLE VIII TABLE IX TABLE X TABLE XI TABLE XIII t) O? M O r¡ Ol TJSJBIiA XV Table XVIII lists some of the characterization data for some representative compounds of this invention.

TABLE XVIII NMR data H, 1J No. NMR (CDC13, 300 MHz) ppm 1-1 (CDCl 3 + CD 3 OD) 4.04 (3H, s), 6.19 (1H, s), 7.57 (1H, d, J = 8.6 Hz) ) 1-2 (DMSO-d6), 3.30 (2H, broad s), 6.54 (1H, s), 8.12 (1H, d, J = 9.2 Hz) 1-3 (CDCl3 + CD3OD) 3.85 (3H, s), 6.2 (1H, s), 6.58 (1H, d, J = 9.4 Hz) 1-4 3.57 (3H, broad c, J = l , 2 Hz), 3.86 (3H, s), 4.04 (2H, broad s), 6.37 (1H, s), 6.66 (1H, d, J = 9.4 Hz) 1-5 3.55 (3H, broad c, J = 1, Hz), 4.04 (3H, s), 6.33 (1H, s), 7.51 (1H, d, J = 8, 6 Hz) 1-6 3.57 (3H, broad c, J = 1, Hz), 6.38 (1H, s), 7.85 (1H, d, J = 8.0 Hz), 10, 57 (1H, broad) 1-7 3.52 (3H, c, J = 0.7 Hz), 3.82 (3H, s), 4.13 (2H, broad), 6.32 (1H, s) ), 6.79 (1H, d, J = 9, 1 Hz) 1-8 3.48 (3H, s), 4.90 (3H, broad), 6.30 (1H, s), 6.69 (1H, d, J = 9.0 Hz) 1-9 (Acetone-d6) 3.68 (3H, s broad, J = 1, 4 Hz), 4.05 (3H, s), 8.03 ( 1H, d, J = 9, l Hz) 1-10 3.52 (3H, broad s), 3.86 (3H, s), 4.05 (2H, broad s), 6.66 (1H, d) , J = 9, 7 Hz) 1-11 2.74 (6H, s), 3.57 (3H, s broad), 3.84 (3H, s), 6.35 (1H, s), 7, 01 (1H, d, J = 8.8 Hz) 1-12 4.05 (3H, s), 4.61 (2H, S), 6.24 (1H, s), 7.52 (1H, d) , J = 8.6 Hz) 1-13 3.78 (3H, s), 5.24 (2H, s), 5.41 (2H, broad s), 6.21 (1H, s), 6, 56 (1H, d, J = 9, 5 Hz) -14.143 (3H, m), 4.06 (3H, s), 4.31 (2H, m), 6.32 (1H, s) , 7.56 (1H, m) -15.15 (3H, m), 3.85 (3H, s), 3.35 (2H,), 6.48 (1H, s), 6.55 ( 1H, m) -16 (CDC13 + CD30D) 3.55 (3H, broad c, J = 1, Hz), 6, 36 (1H, s), 6.61 (1H, d, J = 9.2 Hz) -17 3.57 (3H, d, J = 1, 2 Hz), 6.38 (1H, s), 7 , 67 (1H, d, J = 8.3 Hz), 10.47 (1H, broad s) 1-18 3.51 (3H, broad c, J = 0.9 Hz), 4.94 (2H, s), 5.66 (2H, broad s), 6.39 (1H, s), 6.65 (1H, d, J = 9, 4 Hz) 1-19 2.58 (1H, m), 3.55 (3H, c squared, J = 1, 3 Hz), 4.17 (2H, broad s), 4.7 (2H, d, J = 2.4 Hz), 6.35 (1H, s) 6.65 (1H, d, J = 9.3 Hz) 1-20 3.57 (3H, d, J = 0.8 Hz), 3, 78 (3H, s), 4.02 (2H, broad s), 4.65 (2H, dd, J = 4.4, 1.9 Hz), 6.28 (1H, td, J = 15.7 , 1.9 Hz), 6.65 (1H, d, J = 9, 3 Hz), 7.01 (1H, td, J = 15.7, 4.4 Hz) 1-21 1.63-1 , 94 (8H, m), 3.55 (3H, s), 3.97 (2H, s), 4.8 (1H, m), 6.34 (1H, s), 6.65 (1H, d, J = 9.6 Hz) 1-22 3.54 (3H, broad c, J = 1, Hz), 3.94 (2H, broad s), 5.0 (2H, s), 6.34 (1H, s), 6, 69 (1H, d, J = 9, 4 Hz), 7.3-7.5 (5H, m) 1-23 3.58 (3H, broad c, J = 1, 2 Hz), 4.15 ( 2H, broad s), 6.38 (1H, s), 6.78 (1H, d, J = 9.2 Hz), 7.22 (1H, m), 8.36 (2H, m) 1-30 3.52 (3H, broad c, J = 1, Hz), 3.75 (3H, s), 6.31 (1H, s), 7.22 ( 1H, d, J = 8.8 Hz) 1-31 2.87 (3H, s), 2.96 (3H, s), 3.53 (3H, s), 3.64 (3H, s), 6.30 (1H, s), 6.86 (1H, d, J = 8.9 Hz), 7.68 (1H, s) 1-32 1.83 (4H, m), 3.21 (4H , m), 3.55 (3H, broad s), 3.72 (3H, s), 6.34 (1H, s), 6.86 (1H, d, J = 8.9 Hz) -33 1 , 27 (3H, t, J = 7, 1 Hz), 4,20 (2H, c, J = 7, 1 Hz), 6,21 (1H, s), 7,62 (1H, d, J = 8.8 Hz) -34 1.26 (3H, t, J = 7, l Hz), 4.16 (2H, c, J = 7, 1 Hz), 3.53 (3H, s), 6, 35 (1H, s), 7.70 (1H, d, J = 8, 5 Hz) -36 2.40 (3H, d, J = 1, 1 Hz), 3.54 (3H, d, J = 1, 3 Hz), 6.33 (1H, s), 7.51 (1H, d, J = 8.5 Hz) -37.23 (3H, d, J = 0.9 Hz), 3, 57 (3H, d, J = 1, Hz), 6.38 (1H, s), 6.74 (1H, d, J = 9.4 Hz) 1-38 3.57 (3H, d, J = l, l Hz), 4.17 (2H, broad s), 6.37 (1H, s), 6.50 (1H, t, J = 74.0 Hz), 6.72 (1H, d, J = 9, 1 Hz) 1-40 3.56 (3H, d, J = 1, Hz), 3.96 (3H, s), 6.36 (1H, s), 7.07 (1H, d, J = 8.7 Hz) 1-41 3.54 (3H, d, J = 1, Hz), 6.38 (1H, s), 6.89 (2H, m), 7.00 ( 1H, dd, J = 7.9, 1.5 H z), 7.26 (1H, td, J = 7, 7 1.5 Hz), 7.85 (2H, broad s) 1-42 3.55 (3H, d, J = 1, 2 Hz), 6.38 (1H, s), 7.38 (1H, dd , J = 7.9, 1.4 Hz), 7.66 (1H, dt, J = 7, 9, 1.4 Hz), 7.79 (1H, dt, J = 7.9, 1.4 Hz), 8.27 (1H, dd, J = 7, 9, 1.4 HZ) 1-43 3.56 (3H, d, J = 1, 1 HZ), 6.39 (1H, s), 7.58 (1H, d, J = 8.2 Hz), 8.05 (1H, dd, J = 8.2, 1.8 Hz), 8.54 (1H, d, J = 1, 8 Hz) 1-44 3.57 ( 3H, d, J = 1, Hz), 6.39 (1H, s), 7.13 (3H, m) 1-45 3.58 (3H, d, J = 1, 2 Hz), 6.38 (1H, s), 7.87 (1H, s), .61 (1H, broad s) 1-46 3.55 (3H, d, J = 1, 2 Hz), 3.93 (3H, s), 6.37 (1H, s), 7.27 (2H, m), 7.77 (1H, dd, J = 2, 1, 1.0 Hz 1-47 3.50 (3H, d, J = 0.9 Hz), 3.81 ( 3H, s), 3.96 (2H, s), 6.31 (1H, s), 6.88 (1H, s) 1--48 1.27 (3H, t, J = 7, l Hz), 1.58 (3H, d, J = 6.8 Hz), 3.55 (3H, d, J = 1, Hz), 3.64 (2H, broad s), 4.22 (2H, m), 4.70 (1H, c, J = 6, 8 Hz), 6.36 (1H, s), 6.38 (2H, m), 6.88 (1H, d, J = 9.2 Hz) 1--49 1.29 (3H, t, J = 7, l Hz), 1.68 (3H, d, J = 6.8 Hz), 3.54 (3H, d, J = 1.0 Hz), 4.26 (2H, m), 4, 82 (1H, c, J = 6.8 Hz), 6.36 (1H, s), 7.25 (2H, m), 7.74 (1H,) 1--50 3.57 (3H, c, J = 1, 2 Hz), 6.38 (1H, s), 6.65 (1H, t, 71.1 Hz), 7.37 (1H, dd , J = 9.3, 2.7 Hz), 7.85 (1H, dd, J = 2.7, 2.5 Hz) 1--51 3.49 (3H, d, J = 1.0 Hz ), 6.30 (3H, m), 6.42 (1H, t, J = 73.2 Hz), 7.8 (2H, broad s) 1--52 3.57 (3H, d, J = 1, 2 Hz), 6.40 (1H, s), 7.57 (1H, d, J = 8.2 Hz), 8.04 (1H, dd, J = 8.2, 1.6 Hz) , 8.53 (1H) 1--53 1.27 (1.5H, t, J = 7, 1 Hz), 1.28 (1.5H, t, J = 7, 1 Hz), 1.44 (1.5H, d, J = 6.9 Hz), 1.45 (1.5H, d, J = 6.9 Hz), 3.58 < 3H, s), 4.08 (1H, m), 4.20 (2H, c, J = 7, 1 Hz), 4.39 (0.5H, d, J = 7.2 Hz), 4, 43 (0.5H, d, J = 7.2 Hz), 6.26 (1H, m), 6.39 (2H, m), 6.50 (1H, t, J = 73.3 Hz) 1--54 1.27 (1.5H, t, J = 7, l Hz), 1.28 (1.5H, t, J = 7, 1 Hz), 1.44 (1.5H, d, J = 6.9 Hz), 1.46 (1.5H, d, J = 6.9 Hz), 3.57 (3H,), 4.11 (1H,), 4.22 (2H, m) , 4.35 (0.5H, d, J = 7.4 Hz), 4.43 (0.5H, d, J = 7, 1 Hz), 6.36 (0.5H, s), 6, 38 (0.5H, s), 6.49 (1H,), 6.62 (1H, dd, J = 9, 1, 2.0 Hz) 1--55 1.22 (1.5H, t, J = 7, l Hz), 1.23 (1.5H, t, J = 7, 1 Hz), 1.36 (1.5H, d, J = 6.9 Hz), 1.38 (1, 5H, d, J = 6, 9 Hz), 3.55 (3H, m), 3.82 (1.5H, s), 3.86 (1.5H, s), 4.0-4.4 (4H, m), 6.36 (1H, s), 6.76 (0.5H, d, J = 9, 1 Hz), 6.79 (0.5H, d, J = 9, l Hz) 1--56 4.73 (2H, broad s), 5.50 (3H, broad), 6.16 (1H, s), 6, 53 (1H, d, J = 9, 3 Hz) --57 I 4.42 (2H, broad s), 4.70 (2H, broad s), 4.72 (2H, e), 6, 16 (1H, s), 6.60 (1H, d, J = 9, 1 Hz) --58 3.77 (3H, s), 4.64 (2H, broad s), 4.87 (2H, s), 5.28 (2H, broad s), 6.17 (1, s), 6.52 (1H, d, J = 9.2 Hz) --59 1.29 (3H, t, J = 7, l Hz), 3.55 (3H, c, J = 1.0 Hz), 4.23 (2H, c, J = 7, l Hz), 4.64 (2H, s), 4.82 (2H, broad s), 6.35 (1H, s), 6.60 (1H, d, J = 9.2 Hz) --60 1.27 (3H, t, J = 7, l Hz), 1659 (1.5H, d, J = 7.0 Hz), 1.666 (1.5H, d, J = 7.0 Hz), 3, 55 (3H, s), 4.20 (2H, J = 7, l Hz), 4.73 (1H, m), 6,340 (0,5H, s), 6,355 (0,5H, s), 6 , 61 (1H, d, J = 9.3 Hz) -61.141 (3H, t, J = 7.0 Hz), 3.52 (3H, c, J = 1.0 Hz), 4, 04 (2H, c, J = 7.0 Hz), 4.10 (2H, broad s), 6.32 (1H, s), 6.62 (1H, d, J = 9, 5 Hz) -62 1.16 (3H, t, J = 7, l Hz), 1.42 (3H, t, J = 7, 1 Hz), 2.99 (2H, c, J = 7, l Hz), 3, 57 (3H, c, J = 1, Hz), 4.03 (2H, c, J = 7, 1 Hz), 4.14 (1H, broad s), 6.35 (1H, s), 6 , 63 (1H, d, J = 9.4 Hz) -63.35 (6H, d, J = 6.2 Hz), 3.55 (3H, c, J = 1, 2 Hz), 3, 95 (2H, broad s), 4.50 (1H, c, J = 6.2 Hz), 6.34 (1H, s), 6.66 (1H, d, J = 9.4 Hz) --64 1.06 (3H, t, J = 6.3 Hz), 1.37 (6H, d, J = 6.2 Hz), 3.57 (3H, c, J = 1, 2 Hz), 3.83 (2H, broad s), 4.52 (1H, c, J = 6.2 Hz), 6, 35 (1H, s), 6.70 (1H, d, J = 9.3 HZ) --65 7.62 (1H, d, J = 8.5 Hz), 8.37 (1H, 2d, J = 2, 6 Hz, 8.4 Hz), 8.83 (1H, d, J = 2.6 Hz) --66 3.56 (3H, s), 6.37 (1H, s), 6, 86 (1H, d, J = 8.4 Hz), 7.77 (1H, d, J = 8.4 Hz), 10.75 (1H, broad) -67 3.56 (3H, S), 6.37 (1H, s), 8.55 (1H, s) --68 3.56 (3H, s), 6.39 (1H, s), 7.45 (1H, d, J = 8, 7 Hz), 7.64 (1H, 2d, J = 1.7 Hz, 8.7 Hz), 8.13 (1H, d, J = 1.7 Hz) -69 4.15 (3H, s) , 6.14 (1H, s), 8.51 (1H, broad) -70 6.26 (1H, s), 7.62 (1H, 2d, J = 6, 1 Hz, 8.3 Hz), 8.3 (1H, broad) -71 3.56 (3H, s), 4.8 (3H, broad), 6.38 (1H, s), 6.59 (1H, d, J = 8.7 Hz), 6.85 (1H, d, J = 8.7 Hz) -72.56 (3H, s), 3.89 (3H, s), 6.37 (1H, s), 6.75 (1H, d, J = 8.7 HZ), 6.87 (1H, d, J = 8.7 Hz) -73 3.55 (3H, s), 3.75 (2H, s), 6, 36 (1H, s), 6.73 (2H, m), 7.01 (1H, 2d, J = 2.4 Hz, 6.9 Hz) -1.02 (3H, s), 3.57 (3H, broad c, J = l, l Hz), 3.86 (3H, s), 6.30 (1H, s), 7.22 (1H, d, J = 9.6 Hz) -2.29 (3H, s), 2, 33 (3H, s), 3.53 (3H, broad s), 3.78 (3H, s), 6.3 (1H, s), 7.42 (1H, d, J = 8.8 Hz) -3,14 (9H, s), 3,56 (3H, s), 3,82 (3H, s), 6,29 (1H, s), 7,19 (1H, d, J = 9, 0 Hz), 7.61 (1H, broad s) -4 3-, 49 (3H, c wide, J = 1.0 Hz), 3.75 (3H, s), 5.70-5.79 ( 2H, m), 6.26 (1H, s), 6.40-6.55 (4H,), 7.42 (1H, d, J = 8.7 Hz) -5 1.95 (3H, s ), 3.55 (3H, broad s), 3.84 (3H, s) 5.45 (1H, s), 5.70 (1H, s), 6, 7 (1H, s), 7, 20 (1H, d, J = 9.0 Hz), 7.62 (1H, broad s) --6.90 (3H, s), 1.91 (3H, s), 3.49 (3H, s wide), 3.79 (3H, s), 5.46 (2H, s), 5.64 (1H, s), 5.66 (1H, s), 6.27 (1H, s), 7 , 30 (1H, d, J = 8.8 Hz) --7.86 (3H, s), 2.05 (1H, s), 3.56 (3H, broad s), 3.82 (3H , s), 5.66 (1H, broad s), 6.27 (1H, s), 7.17 (1H, d, J = 9.0 Hz), 7.23 (1H, broad s) - 8 1.85 (6H, m), 2.12 (6H,), 3.47 (3H, broad c, J = 1.0 Hz), 3.77 (3H, s), 5.91 (1H, ), 5.98 (1H, m), 6.25 (1H, s), 7.34 (1H, d, J = 8.7 Hz) - 9 (CDC13 + CD30D) 3.86 (3H, s), 6.16 (1H, s), 7.37 (1H, d, J = 8.9 Hz) -10 3.54 (3H, broad s), 3.86 (3H, s), 6, 31 (1H, s) 7.32 (1H, d, J = 9.0 Hz) -11 (CDC13 + CD30D) 3.55 (3H, broad s), 4.87 (2H, s), 6.35 (1H, s), 7.44 (1H, d, J = 8.7 Hz) -12 (CDC13 + CD30D) 3.59 (3H, broad s), 3.87 (3H, s), 7.37 (1H, d, J = 8.8 Hz) 2-13 3.56 (3H, c wide, J = l, l Hz), 3.89 (3H, s), 4.08 (2H, s), 6.3 (1H, s), 7.25 (1H, d, J = 9 Hz) 2-14 3.52 (3H, broad c, J = l, l Hz), 3.74 (2H, m) , 3.85 (3H, s), 6.39 (1H, s), 7.53 (1H, d, J = 9, 3 Hz), 9.03 (1H,) 2-15 3.56 (3H , s), 3.91 (3H, s), 3.95 (3H, s) 7.24 (1H, d, J = 9.0 Hz), 9.00 (1H, s) 2-16 , 27 (3H, t, J = 7, l Hz), 1.28 (3H, t, J = 7, 1 Hz), 3.42 (2H, s), 3.57 (3H, broad s), 4.04 (2H, s), 4.10-4.30 (4H, m), 6.40 (1H, s), 7.33 (1H, d, J = 9.8 Hz), 8, C7 (1H, s) 2-17.95 (2H, m), 1.10 (2H,), 1.50 (1H, m), 3.55 (3H, s), 6.37 (1H, s), 7.22 (1H, d, J = 9, 0 Hz), 7.92 (1H, broad s), 8.41 (1H, broad s) 2-18-18.70-1.20 ( 8H,), 1.96 (1H,), 2.15 (1H, m), 3.54 (3H, e wide), 375 (3H, e), 6.35 (1H, e), 7.38 (1H, d, J = 8.6 Hz) 2- -19.40 (5H,), 1.70 (5H, m) , 2.25 (1H, m), 3.32 (3H, e), 3.82 (3H, 8), 6.34 (1H, 8), 7.17 (1H, d, J = 9.0 Hz), 7.68 (3H, e) 2-20.20 (10H, m), 1.70 (10H, m), 2.50 (2H, m), 3.50 (3H, e) , 3.68 (3H, s), 6.31 (1H, e), 7.36 (1H,) 2-21.27 (3H, s), 3.44 (3H, s), 3.55 (3H, e wide), 4.18 (3H, s), 6.33 (1H, s), 7.43 (1H, d, J = 8.8 Hz) 3.2 (3H, e), 3.55 (3H, s), 3.96 (3H, s), 6.35 (1H, s), 6.48 (1H, broad s), 7.29 ( 1H, d, J = 8.8 Hz) 2-2222 3.52 (3H, broad s), 3.64 (3H, e), 6.29 (1H, s), 6.85 (1H, d, J = 9, l Hz), 7, 4 (5H, m), 7.68 (1H, s) - 23.29 (3H, s), 3.52 (3H, s), 3.82 (3H, s), 6.23 (1H , s), 7.20 (1H, d, J = 9.0 Hz), 7.32 (2H, m), 7.53 (2H, m), 8.02 (1H, s) - 24 2 , 42 (3H, s), 3.53 (3H, 8), 3.82 (3H, s), 6.22 (1H, S), 7.20 (1H, d, J = 9.0 Hz) , 7.26 (2H, d, J = 7.8 Hz), 7.67 (2H, d, J = 7.8 Hz), 7.91 (1H, s) - 25 2.32 (3HX2, s), 3.28 (3H, s), 3.82 (3H, e), 6.02 (1H, s), 7.10 (4H, d, J = 7.9 Hz), 7.26 ( 1H, d, J = 9.0 Hz), 7.73 (4H, m) - 26 2.40 (3H, s), 3.44 (3H, s), 3.54 (3H, d, J = 1, 1 Hz), 6.29 ( 1H, e), 6.55 (1H, 8 wide), 7.18 (1H, d, J = 8.9 Hz), 7.25 (2H, d, J = 8.3 Hz), 7.68 (2H, d, J = 8.3 Hz) - 27 1.26 (3H, t, J = 7.7 Hz), 2.71 (2H, c, J = 7.7 Hz), 3.54 (3H, e), 3.83 (3H, e), 6.23 (1H, s), 7.21 (1H, d, J = 9.0 Hz), 7.29 (2H, d, J = 8.2 Hz), 7.70 (2H, d, J = 8.2 Hz), 7.86 (1H, broad s) --28.16 (3H, t, J = 7.6 Hz), 2.71 (2H, c, J = 7.6 Hz), 3.51 (3H, e wide), 4.78 (2H, s), 6.25 (1H, e), 7.28 (3H, m), 7.73 (2H,), 7.84 (1H, e wide) - 29 0.95 (6H, t, J = 7.2 Hz), 1.66 (4H, m), 2, 64 (4H, m), 3.53 (3H, broad s), 3.83 (3H, e), 6.23 (1H, e), 7.21 (1H, d, J = 9.3 Hz) , 7.27 (4H, m), 7.70 (2H, m), 8.00 (2H,) --30.35 (9H, s), 3.55 (3H, s), 3.83 (3H, e), 6.23 (1H, 8), 7.20 (1H, m), 7.49 (2H, d, J = 8.6 Hz), 7.73 (2H, d, J = 8.6 Hz), 7.88 (1H, broad s) --31 3.54 (3H, s), 3.83 (3H, 8), 5.40 (1H, d, J = 10.9 Hz ), 5.87 (1H, d, J = 17.6 Hz), 6.78 (1H, dd, J = 17.6, 10.9 Hz), 7.22 (1H, d, J = 9, 0 Hz), 7, 49 (2H, d, J = 8.2 Hz), 7.75 (1H, d, J = 8.2 Hz), 8.01 (1H, e wide) -32 2.31 (3H, e), 2.32 (3H, s), 3.54 (3H, d, J = 1.0 Hz), 3.82 (3H, s), 6.23 (1H, s), 7.19 (1H, d) , J = 9, 1 Hz), 7.22 (1H, d, J = 7.8 Hz), 7.50 (1H, dd, J = 7, 8, 1.7 Hz), 7.56 (1H , s wide), 7.86 (1H, e wide) -33 3.62 (3H, s), 3.84 (3H, s), 6.25 (1H, s), 7.25 (1H, d) , J = 8.9 Hz), 7.75 (2H, d, J = 8.3 Hz), 7.89 (2H, d, J = 8.3 Hz), 7.92 (1H, s broad) -34 3.54 (3H, broad s), 3.84 (3H, e), 6.26 (1H, e), 7.30 (1H, d, J = 9.3 Hz), 7.72 ( 4H,), 7.94 (2H, m), 8.17 (2H,) -36 3.56 (3H, d, J = 1, Hz), 3.85 (3H, e), 4.64 (2H, e), 6.25 (1H, e), 7.24 (1H, d, J = 9, 0 Hz), 7.52 (2H, d, J = 8.3 Hz), 7.79 (2H, d, J = 8.3 Hz), 7.91 (1H, e wide) -37 3.53 (3H, s), 3.83 (3H, s), 6.25 (1H, s) , 7.20 (1H, d, J = 9.0 Hz), 7.45 (3H, m), 7.63 (4H, m), 7.84 (2H, d, J = 8.2 Hz) , 8.13 (1H, e) -38.32 (3H, s), 3.86 (3H, e), 6.08 (1H, e), 7.52 (15H, m), 7.95 (4H,) -39 3.56 (3H, broad s), 3.89 (3H, e), 6.27 (1H, s), 7.15-7.3 (2H, m), 7.24 (1H, d , J = 9, 1 Hz), 7.54 (1H,), 7.92 (1H, in), 8.43 (1H, d, J = 13.8 Hz) -40 3.53 (3H, s width), 3.83 (3H, e), 6.23 (1H, e), 7.12 (2H, m), 7.22 (1H, d, J = 9, 1 Hz), 7.79 ( 2H,), 7.97 (1H, broad) -41 3.57 (3H, broad c, J = 1, Hz), 3.9 (3H, s), 6.29 (1H, e), 7.2 (1H, m), 7.26 (1H, d, J = 9, 1 Hz), 7.36 (1H, m), 7.63 (1H, m), 8.29 (1H, d) , J = ll, l Hz) -42 3.56 (3H, e wide), 3.89 (3H, e), 6.27 (1H, e), 6.97 (2H, m), 7.25 (1H, d, 3 = 9 Hz), 7.97 (1H,), 8.37 (1H ,. d wide, J = 13.3 Hz) -43.44 (3H, broad s), 3.96 (3H, e), 6.24 (1H, e), 6.64 (2H, m), 6 , 86 (2H,), 7.35 (1H, d, J = 8, 8 Hz), 7.78 (2H,) - 44 3.88 (3H, e), 6.26 (1H, e) , 6.98 (2H,), 7.23 (1H, d, J = 9 Hz), 7.96 (1H, m), 8.46 (1H, m) - 45 3.43 (3H, c width, J = 1, 3 Hz), 5.1 (2H, e), 6.36 1H, s), 6.9-7.15 (4H, m), 7.77 (1H, d, J = 9, 1 Hz), 7.7-7.9 (2H, m) - 46 3.52 (3H, e), 3.91 (3H, 8), 6.75-7.05 (2H, m ), 6.95 (1H, e), 7.39 (1H, d, J = 8, 9 Hz), 8.03 (1H, m), 8.56 (1H, m) --47 3.55 (3 H, broad s), 3,91 (3 H, s), 6,32 (1 H, s), 6,93 (2 H, m), 7,25 (1 H, d, J = 8, 9 Hz), 7.39 (1H, m), 8.03 (1H, broad s) 2--48 3.55 (3H, broad c, J = 1.0 Hz), 3.83 (3H, e), 6, 26 (1H, s), 7.24 (1H, d, J = 9, l Hz), 7.25 (1H,), 7.54 (1H,), 7.65 (1H, m), 8, 05 (1H, e wide) 2--49 3.39 (3H, broad s), 3.77 (3H, 8), 6.1 (1H, s), 7.10-7.40 (2H, m), 7.34 (1H , d, J = 8.8 Hz), 7.60-8.00 (4H, m) 2--50 3.54 (3H, broad s), 3.81 (3H, s), 6.26 ( 1H, s), 7.01 (1H, m), 7.25 (1H, d, J = 9.3 Hz), 7.31 (2H,), 8.28 (1H, e) 2--51 3.43 (3H, broad s), 3.79 (3H, s), 6.15 (1H, e), 6.95-7.75 (7H, m) 2--53 3.56 (3H, d, J = 1, 2 Hz), 3.91 (3H, s), 6.32 (1H, e), 7.26 (1H, d, J = 9.0 Hz), 7.35 1H, ddd, J = 8.6, 6.1, 2.5 Hz), 7.42 (2H,), 7.52 (1H, dd, J = 7.4 Hz), 7.83 (1H, e wide) 2--54 3.53 (3H, s ), 3.82 (3H, s), 6.26 (1H, e), 7.22 (1H, d, J = 9.0 Hz), 7.39 (1H, dd, J = 7.8, 7.9 Hz), 7.53 (1H, m), 7.62 (1H, m), 7.77 (1H, m), 8.06 (1H, broad s) 2--55 3.36 (3H, e), 3 , 81 (3H, s), 6.11 (1H, e), 7.30 (3H,), 7.43 (2H, m), 7.76 (4H, m) -56 3.53 (3H , s), 3.83 (3H, s), 6.23 (1H, s), 7.23 (1H, d, J = 9.0 Hz), 7.44 (2H, d, J = 8, 7 Hz), 7.72 (2H, d, J = 8.7 Jz), 7.92 (1H, s) 2--57.32 (3H, S), 3.78 (3H, s), 6.06 (1H, s), 7.34 (5H, m), 7.80 (4H,) 2--58 3.56 (3H, d, J = 1.0 Hz), 3.89 (3H , s), 6.32 (1H, e), 7.27 (1H, d, J = 9.0 Hz), 7.31 (1H, dd, J = 8, 1, 1.9 Hz), 7 , 47 (2H,), 7.92 (1H, e wide) 2--59 3.55 (3H, d, J = l, l Hz), 3.84 (3H, e), 6.25 (1H , s), 7.25 (1H, d, J = 9, l Hz), 7.54 (1H, d, J = 8, l Hz), 7.60 (1H, dd, J = 8.3, 2.0 Hz), 7.88 (1H, broad s), 7.89 (1H, d, J = 2.0 Hz) 2--60 3.54 (3H, broad s), 3.83 (3H , s), 6.26 (1H, s), 7.24 (1H, d, J = 9.0 Hz), 7.34 (2H, m), 7.6-7.75 (2H, m) , 7.92-8.25 (4H, m) 2 - 61 3.53 (3H, s), 3.82 (3H, 8), 6.23 (1H, s), 7.22 (1H, d, J = 9.0 Hz), 7.61 (4H, m), 7.95 (1H, e) 2--62.33 (3H, s), 3.80 (3H, e), 6 , 06 (1H, s), 7.31 (1H, d, J = 9.0 Hz). 7.51 (4H, m), 7.73 (4H,) 2--63 3.54 (3H, d, J = l, l Hz), 3.83 (3H, s), 3.87 (3H , 8), 6.22 (1H, e), 6.95 (2H, d, J = 8.8 Hz), 7.21 (1H, d, J = 9, l Hz), 7.75 (2H , d, J = 8.8 Hz), 7.78 (1H, e wide) 2--64 1.44 (3H, t, J = 7.0 Hz), 3.52 (3H, s), 3 , 82 (3H, 8), 4.06 (2H, c, J = 7.0 Hz), 6.22 (1H, e), 6.90 (2H, d, J = 9.0 Hz), 7 , 20 (1H, d, J = 9.0 Hz), 7.73 (2H, d, J = 9.0 Hz), 7.91 (1H, s) 2--66 3.55 (3H, d , J = 1.0 Hz), 3.84 (3H, e), 6.25 (1H, 8), 7.25 (1H, d, J = 9, l Hz), 7.51 (2H, d , J = 8, 6 Hz), 7.85 (2H, d, J = 8.6 Hz), 7.88 (1H, e wide) 2--67 3.85 (3H, e), 6.22 (1H, s), 7.25 (1H, d, J = 9.9 Hz), 7.76 (2H, d, J = 8.4 Hz), 7.85 (2H, d, J = 8, 4 Hz), 7.96 (1H, broad s) --69 3.40 (3H, broad s), 3.79 (3H, s), 6.12 (1H, e), 7.36 (1H, J = 8.7 Hz), 8.06 (4H, m), 8.25 (4H, m) - 70 3.50 (3H, 8 wide), 3.87 (3H, s), 6.32 (1H, 8), 7.51 (1H, d, J = 8.8 Hz), 9.07 (2H, m), 9.12 (1H,), 9.91 (1H, broad s) - 71.33 (3H, s), 3.77 (3H, s), 7.20 (4H, m), 7.31 (1H, d, J = 8.8 Hz), 7.92 (4H, m) - 72.54 ( 3H, 8), 3.83 (3H, s), 6.24 (1H, e), 7.25 (3H, m), 7.82 (2H,) 8.02 (1H, s) -73 3.54 (3H, broad s), 3.83 (3H, s), 6.05 (2H, s), 6.23 (1H, e), 6.85 (1H, d, J = 7, 8 Hz), 7.21 (1H, d, J = 8.8 Hz), 7.25-7.34 (2H,), 7.80 (1H, broad s) --74 3.52 (3H, s ), 3.84 (3H, s), 6.25 (1H, s), 7.24 (1H, d, J = 9.0 Hz), 7.50 (4H, m), 7.90 (3H , m), 8.20 (1H, broad s) --75 3.64 (3H, s), 3.85 (3H, 8), 6.24 (1H, s), 7.24 (1H, d) , J = 9.0 Hz), 7.80 (7H, m), 8.32 (1H, s) - 76 3.87 (3H, e), 6.1 (1H, e), 7.31 (1H, d, J = 9, 0 Hz), 7.60 (2H,), 7.80-8.05 (5H,), 8.38 (1H, s) -77 3.83 (3H, S), 4.69 (2H, s), 6.21 (1H, S), 7.35 (1H, d, J = 8.9 Hz), 7.50-7.60 (3H, m), 7.80-7.85 (4H,), 8.07 (1H, s) -78 3.56 (3H, e), 3.86 (3H, 8), 6.28 (1H, e), 6.49 (1H, d, J = 15.6 Hz), 7.21 (1H, d, J = 9.0 Hz), 7.39 (4H, m), 7.50 (2H,), 7 , 63 (1H, d, J = 15.6 Hz) - 79 3.57 (3H, s), 3.86 (3H, s), 6.28 (1H, s), 6.54 (1H, d, J = 15.7 Hz), 6.84-6.94 (3H, m), 7.22 (1H, d, J = 9.0 Hz), 7.36 (1H, broad s), 7 , 48 (1H, c, J = 7, 7 Hz), 7.67 (1H, d, J = 15.7 Hz) -80 2.41 (3H, s), 3.57 (3H, s), 3.86 (3H, s), 6.29 (1H, 8), 6, 40 (1H, d, J = 15.4 Hz), 7.19-7.32 (4H, m), 7.33 (1H, broad s), 7.53 (1H, d, J = 7.2) Hz), 7.93 (1H, d, J = 15.4 Hz) - 81 2.12 (3H, d, J = 1, 3 Hz), 3.57 (3H, d, J = 0.9 Hz), 3.88 (3H, s), 6.29 (1H, s), 7.20 (1H, d, J = 9, 1 Hz), 7.36 5H, m), 7.66 (1H , s wide) --82 3.57 (3H, broad s), 3.85 (3H, e), 6.29 (1H, 8), 6.48 (1H, d, J = 15.6 Hz), 7.16 (1H, d, J = 9.0 Hz), 7.28 (2H, m), 7.40 (1H, dd, J = 7, 9, 1.6 Hz), 7.53 (1H, dd, J = 7.4, 1.6 Hz), 7.67 (1H, broad s), 7.98 (1H, d, J = 15.6 Hz ) --83 3.46 (3H, broad s), 6.24 (1H, s), 6.80 (1H, d, J = 15.5 Hz), 6.91 (1H, d, J = 15 , 5 Hz), 7.30 (4H, m), 7.39 (2H,), 7.45 (1H, d, J = 8.8 Hz), 7.56 (1H dd, J = 7.6 , 1.8 Hz), 7.59 (1H, dd, J = 7.6, 1.8 Hz), 8.18 (1H, d, J = 15.5 Hz), 8.20 (1H, d , J = 15, 5 Hz) --84 3.56 (3H, e wide), 3.84 (3H, s), 6.29 (1H, e), 6.45 (1H, d, J = 15 , 6 Hz), 7.18 (1H, d, J = 9, 0 Hz), 7. 54 (2H, d, J = 8.6 Hz), 7.40 (2H, d, J = 8.6 Hz), 7.55 (1H, d, J = 15.6 Hz), 7.59 (1H, e wide) - 85 3.56 (3H, broad s), 3.84 (3H, s), 3.85 (3H, s), 6.28 (1H, e), 6.35 (1H, d) , J = 15.5 Hz), 6.89 (2H, d, J = 8.7 Hz), 7.19 (1H, d, J = 9.0 Hz), 7.35 (1H, e wide) , 7.45 (2H, d, J = 8.7 Hz), 7.58 (1H, d, J = 15.5 Hz) - 86 2.60 (2H, c, J = 7.7 Hz) , 2.91 (2H, t, J = 7.7 Hz), 3.56 (3H, s), 3.69 (3H, s), 6.26 (1H, 8), 7.1-7, 3 (6H,) - 87 2.66 (2H,), 2.92 (2H, m), 3.55 (3H, s), 4.52 (2H, e), 6.28 (1H, e ), 7.1-7.4 (6H, m) -88 1.90 (2H, tt, J = 7.5, 7.4 Hz), 2.29 (2H, d, J = 7, 4 Hz), 2.61 (2H, t, J = 7.5 Hz), 3.52 (3H, d, J = 0.7 Hz), 3.84 (3H, s), 6.28 (1H, 8), 7.13-7.32 (7H, m) -89 3.54 (3H, s), 3.82 (3H, s), 4.02 (2H, e), 4.55 (2H , s), 6.15 (1H, s), 7.16 (1H, d, J = 9.0 Hz), 7.4 (5H, m), 8.55 (1H, s) 2--90 3.56 (3H, d, J = 1, Hz), 3.87 (3H, 8), 6.26 (1H, s), 6.55 (1H, dd, J = 3.6, 1, 8 Hz), 7.17 (1H, dd, J = 3.6, 0.5 Hz), 7.22 (1H, d, J = 9, 1 Hz), 7.54 (1H, dd, J = l, 8, 0.5 Hz), 8.18 (1H, e wide ) 2--91 2.25 (3H, e), 3.46 (3H, s), 3.81 (1H, e), 6.25 (1H, e), 6.39 (1H, s), 7.18 (1H, d, J = 9.0 Hz), 7.39 (1H, e), 8.30 (1H, S) 2--92 3.56 (3H, d, J = 0.8 Hz), 3.85 (3H, s), 6.28 (1H, s), 6.39 (1H, d, J = 15.2 Hz), 6.48 (1H, dd, J = 3.4 , 1.8 Hz), 6.60 (1H, d, J = 3.4 Hz), 7.19 (1H, d, J = 9, 0 Hz), 7.34 (1H, e wide), 7 , 40 (1H, d, J = 15.2 Hz), 7.48 (1H, d, J = 1, 8 Hz) 2--93 3.45 (3H, e), 3.66 (3H, s ), 3.80 (2H, s), 6.16 (1H, e), 7.00 (4H, m), 7.55 (1H, broad s) 2--94 2.46 (3H, s) , 3.56 (3H, e), 3.88 (3H, e), 6.26 (1H, e), 6.94 (1H, m), 7.20 (1H, d, J = 9.0 Hz), 7.36 (1H,), 7.65 (1H, 8) 2--95 2.45 (3H, S), 3.47 (3H, s), 3.78 (3H, s), 6.17 (1H, 8), 6.70 (1H, m), 7.13 (1H, d, J = 9, 0 Hz), 7.32 (1H,), 7.63 (1H, s) 2--96 2.41 (6H, e), 3.26 (3H, s), 3.78 (3H, s), 5.97 (1H, e), 6.59 (2H, m), 7 , 24 (1H, d, J = 9, 0 Hz), 7.39 (2H, m) 2--97, 3.31 (3H, 8), 3.84 (3H, s), 6.03 (1H , s), 7.05 (2H,), 7.40 (2H, m), 7.70 (3H, m) 2--98 3.54 (3H, s), 3.84 (3H, s) , 6.25 (1H, s), 7.25 (1H, d, J = 9.7 Hz), 7.41 (1H, dd, J = 7.7, 4.8 Hz), 8.01 (1H, d, J = 7.7 Hz), 8.32 (1H, broad s) ), 8.78 (1H, broad s), 9.01 (1H, e wide) 2--100 3.42 (3H, c, J = 1.0 Hz), 3.79 (3H, e), 6.12 (1H, s), 7.35 (1H, d, J = 8.6 Hz), 7.56 (1H, d, J = 8.0 Hz), 7.39 (1H, d, J = 8.0 Hz), 8.15 (1H, dd, J = 8.0, 2.2 Hz), 8.16 (1H, dd, J = 8.0, 2.2 Hz), 8.77 (1H, d, J = 2.2 Hz), 8.91 (1H, d, J = 2, 2 Hz) 2-101 3.59 (3H, c, J = 1, 2 Hz), 6.36 (1H, 8), 6.99 (1H, dd, J = 4.9, 8.3 Hz), 7.27 (1H, d, J = 8.7 Hz), 8.44 (1H, dd, J = 1, 7, 4.8 Hz), 8.6 (1H, dd, J = 1, 7, 8.3 Hz), 9.79 (1H, broad s) 2-102 (CDC13 + CD30D) 3 , 54 (3H, broad s), 6.33 (1H, s), 6.82 (1H, t, J = 5.0 Hz), 7.2 (1H, d, J = 8, 8 Hz), 8.38 (2H, d, J = 5.0 Hz) 2-103 3.55 (3H, c, J = 1.0 Hz), 3.89 (3H, s), 6.26 (1H, e ), 7.22 (1H, d, J = 9, l Hz), 7.45 (3H,), 7.83 (3H,), 7.99 (1H, broad s) 2-104 3.58 ( 3H, e), 3.92 (3H, s), 6.26 (1H, s), 7.20 (1H, d, J = 9.0 Hz), 7.65 (1H,), 7.85 (2H,), 8.17 (2H, m), 8.33 (1H, m), 10.05 (1H, e) 2-105 3.60 (3H, broad s), 3.92 (3H, s), 6.27 (1H, s), 7.27 (1H, d, J = 9.0 Hz), 7.93 (2H, m), 8.20 (2H,), 9.60 (1H, e) , 10.12 (1H, s) 2-106 3.56 (3H, c, J = 0.7 Hz), 3.86 (3H, s), 6.27 (1H, s), 6.95 ( 2H,), 7.41 (1H, d, J = 8.7 Hz), 7.95 (1H,) 2-113 3.65 (3H, c, J = 1.0 Hz), 3.86 (3H, e), 6.26 (1H, d, J = 15.2 Hz), 6.28 (1H, e), 7.05 (1H, dd, J = 5, 0, 3.6 Hz), 7.20 (1H, d, J = 9, 0 Hz), 7.25 (1H, d, J = 3) , 6 Hz), 7.27 (1H, broad s), 7.38 (1H, d, J = 5.0 HZ), 7.75 (1H, d, J = 15.2 Hz) 2-114 3 , 56 (3H, d, J = 0.9 Hz), 6.40 (1H, 8), 7.28 (1H, d, J = 9.21 Hz), 7.50-7.65 (2H, m), 7.70-7.80 (1H, m), 7.80-8.00 (3H,), 8.35 (1H,), 8.63 (1H, broad s) 2-115 3.54 (3H, d, J = 0.9 Hz), 6.24 (1H, 8), 6.51 (1H, t, J = 73, 1 Hz), 7.32 (1H, d, J = 8, 8 Hz), 7.50-7.65 (2H, m), 7.70-7.82 (1H,), 7.85-7.95 (3H, m), 8, 07 (1H, e wide) 8.29 (1H, broad s) 2-116 2.09 (3H, s), 2.14 (3H, s), 3.50 (3H, d, J = 1.0 Hz), 3.79 (3H, s), 4.8-5.0 (4H, m), 6.29 (1H, s), 7.47 (1H, d, J = 8.9 Hz) -117 2.18 (3H, e), 3.56 (3H, d, J = 1, Hz), 3.86 (3H, s), 4, 58 (2H, e), 6.30 (1H, e), 7.24 (1H, d, J = 9.0 Hz) -118 1.40 (3H, t, J = 7, l Hz), 3.56 (3H, d, J = 1.0 Hz), 3.91 (3H, e), 4.39 (2H, c, J = 7, 1 Hz), 6.29 (1H, e), 7.25 (1H, d, J = 9, l Hz), 9.01 (1H, e wide) -119 3.54 (3H, s), 3.72 (3H, 8), 4.56 (2H , s), 6.24 (1H, e), 6.85-7.40 (6H, m), 8.50 (1H, e wide) -120 3.45 (3H, s), 3.85 ( 3H, e), 4.8-5.15 (4H,), 6.27 (1H, s), 6.8-7.0 (6H, m), 7.20-7.30 (4H,) , 7.48 (1H, d, J = 8.7 Hz) -121 3.59 (3H, s), 3.93 (3H, s), 6.35 (1H, s), 7.26 (1H , d, J = 9.0 Hz), 7.40-7.70 (3H,), 8.20 (2H, m), 8.97 (1H, broad s) -122 2.33 (3H, s ), 3.49 (3H, d, J = 0.9 Hz), 6.24 (1H, e), 7.34 (1H, d, J = 9, l Hz), 7.50-7.62 (2H, m), 7.75-7.95 (5H, m), 8.31 (1H, e wide) -123 2.28 (3H, 8), 3.54 (3H, s), 6 , 29 (1H, e), 6.59 (1H, d, J = 15.5 Hz), 7.20-7.50 (6H, m), 7.63 (1H, d, J = 15.5 Hz) - 124.29 (6H, s), 3.56 (3H, 8), 3.93 (3H, s), 6.32 (1H, e), 7.05 (2H, m), 7.20 (2H, m), 7.47 (1H, broad s) -125 3.57 (3H, s), 3.87 (3H, s), 6.29 (1H, e), 6, 62 (1H, d, J = 15.7 Hz), 7.1-7.5 (5H, m), 7.72 (1H, d, J = 15.7 Hz) -126 3.52 (3H, s), 3.80 (3H, s), 6 , 24 (1H, d, J = 15.6 Hz), 6.32 (1H, d, J = 15.6 Hz), 7.11 (1H, broad d, J = 8.8 Hz), 7, 4-7.6 (-1H, m), 7.95 (2H, m) -127 3.56 (3H, 8), 3.86 (3H, s), 3.89 (3H, s), 6.28 (1H, e), 6.64 (1H, d, J = 15.7 Hz), 6.95 (2H, m), 7.19 (1H, d, J = 9.0 Hz), 7.35 (2H, m), 7.46 (1H, dd, J = 7.6, 1.4 Hz), 7.88 (1H, d, J = 15.7 Hz) '- 128 3, 59 (3H, s), 3.88 (3H, s), 6.31 (1H, s), 6.65 (1H, d, J = 15.9 Hz), 7.20 (2H, m), 7.35 (2H, d, J = 8, l Hz), 7.37 (1H, broad s), 7.72 (1H, d, J = 15.9 Hz) -129 2.28 (3H, s ), 2.53 (2H, t, J = 7, 3 Hz), 2.88 (2H, t, J = 7.3 Hz), 3.56 (3H, s), 3.73 (3H, s) ), 6.26 (1H, s), 7.11 (5H, m), 7.35 (1H, broad s) -130 2.33 (3H, s), 2.36 (3H, s), 3 , 57 (3H, s), 3.86 (3H, 8), 6.29 (1H, s), 6.40 (1H, d, J = 15.4 Hz), 7.09 (2H, s wide) ), 7.20 (1H, d, J = 9, 0 Hz), 7.33 (1H, e wide), 7.35 (1H, s), 7.90 (1H, d, J = 15.4 Hz) 2-131 3.54 (3H, d, J = 1.0 Hz), 6.37 (1H, s), 7.21 (1H, d, J = 8.6 Hz), 7.33 (1H, dd, J = 8.6, 2.1 Hz), 7.60 (2H, m), 7.77 (1H, dd, J = 8.6, 1.8 Hz), 7.88 (3H, m ), 7.98 (1H, 8 broad), 8.01 (1H, d, J = 2, 1 Hz), 8.26 (1H, d, J = 1, 3 Hz) 2-132 2.21 ( 3H, s), 2.27 (3H, e), 2.48 (2H, t, J = 7.8 Hz), 2.81 (2H, t, J = 7.8 Hz), 3.57 ( 3H, e), 3.73 (3H, e), 6.27 (1H, e), 6.92 (2H, m), 7.02 (1H, d, J = 7, 6 Hz), 7, 12 (1H, broad d, J = 8.6 Hz), 7.51 (1H, broad s) 2-133 3.55 (3H, d, J = 1.0 Hz), 3.76 (3H, s), 4.52 (2H, s), 6.26 (1H, s), 6.88 ( 2H, dd, J = 9, 1, 2.4 Hz), 7.02 (2H, dd, J = 9, 1, 8.1 Hz), 7.20 (1H, d, J = 9, 0 Hz) ), 8.48 (1H, e wide) 2-134 3.57 (3H, 8), 3.86 (3H, s), 6.28 (1H, e), 6.50 (1H, d, J = 15.5 Hz), 7.23 (1H, d, J = 9, 0 Hz), 7.35 (4H, m), 7.50 (1H, e wide), 7.58 (1H, d, J = 15.5 Hz) 2-135 3.55 (3H, d, J = 1.0 Hz), 3.76 (3H, s), 4.52 (2H, s), 6.26 (1H, e), 6.87 ( 2H, d, J = 9, 0 Hz), 7.20 (1H, d, J = 9.0 Hz), 7.29 (2H, d, J = 9.0 Hz), 8.45 (1H, s wide) 2-136 3.58 (3H, d, J = 1.0 Hz), 3.93 (3H, s), 6.33 (1H, e), 7.26 (1H, d, J = 9, 1 Hz), 7.54 (3H, m), 7.95 (2H, d, J = 8.3 Hz), 8.14 (1H, s), 8.28 (1H, s) 2-137 3.55 (3H, s), 6.37 (1H, e), 6.40 ( 1H, d, J = 15.5 Hz), 7.16 (1H, d, J = 8.6 Hz), 7.19 (1H, broad s), 7.29 (1H, dd, J = 8.5, 1.9 Hz), 7.38 (3H, m), 7.48 (2H,), 7.70 (1H, d, J = 15.5 Hz), 7.99 (1H, broad s) - 139 3.19 (3H, s), 5.98 (1H, s), 7.17 (1H, dd, J = 8.0, 1.2 Hz), 7 , 2-7.6 (7H, m), 7.7-7.9 (6H, m), 7.93 (2H, dd, J = 8.6, 1.7 Hz), 8.53 (2H , s wide) - • 140 3.56 (3H, d, J = 1.0 Hz), 6.40 (1H, s), 7.42 (1H, d, J = 8.3 Hz), 7, 60 (3H, m), 7.78 (1H, dd, J = 8.6, 1.8 Hz), 7.92 (3H,), 8.01 (1H, 8 broad), 8.29 (1H , s wide), 8.38 (1H, d, J = 1, 6 Hz) 2--141 3.59 (3H, s), 6.41 (1H, s), 6.42 (1H, d, J = 15.5 Hz), 7.16 (1H, broad s), 7.38 (4H,), 7.52 (2H, m), 7.59 (1H, dd, J = 8.2, 1 , 7 Hz), 7.75 (1H, d, J = 15.5 Hz), 8.40 (1H, e wide) 2--142 3.47 (3H, s), 6.29 (1H, s ), 7.1-7.9 (11H,), 8.21 (1H, s) 2--143 3.55 (3H, d, J = 1.0 Hz), 3.87 (3H, 8) , 6.38 (1H, s), 6. 89 (1H, dd, J = 8, 9, 2.9 Hz), 7.18 (1H, d, J = 8, 9 Hz), 7.58 (3H, m), 7.79 (1H, dd) , J = 8.6, 1.7 Hz), 7. 90 (4H,), 8.29 (1H, broad s) 2--144 3.54 (3H, d, J = 1.0 Hz), 3.87 (3H, 8), 6.25 (1H, s), 7.60 (3H,), 7.8-8.0 (5H,), 8.30 (1H, broad s) 2--145 3.57 (3H, d, J = 1.0 Hz), 6.38 (1H, 8), 7.12 (1H, dd, J = 9.3, 2.2 Hz), 7 , 59 (2H, m), 7.78 (1H, dd, J = 8.6, 1.8 Hz), 7.8-8.0 (5H, m), 8.28 (1H, broad s) 2--146 1.27 (1.5H, t, J = 7, 1 Hz), 1.27 (1.5H, t, J = 7, 1 Hz), 1.62 (3H, d, J = 6.7 Hz), 3.53 (3H, s), 4.23 (2H,), 4.79 (1H, m), 6.35 (1H, e), 6.85 (1H, m), 7.15 (1H, d, J = 9.0 Hz), 7.5-7.6 (3H, m), 7.77 (1H, dd, J = 8.6, 1.6 Hz), 7.89 (4H, m), 8.26 (1H, 8) 2--147 0.84 (2H,), 1.03 (2H, pt), 1.50 (1H, m), 3.58 (3H, d, J = 1.0 Hz), 6.36 (1H, s), 7.05 (1H, d, J = 7.8 Hz), 7.35 (1H, e wide), 7.88 (1H, e wide) 2--148 3.57 (3H, d, J = 1.0 Hz), 6.39 (1H, s), 6.61 (1H, t, 3 = 12, 1 Hz), 6.88 (1H, dd, J = 10.2, 2.6 Hz), 7.59 (2H, m), 7.76 (2H,), 7.90 (3H ,), 8.05 (1H, e wide), 8, 27 (1H, s) - -149 3.56 (3H, d, J = 1.0 Hz), 6.38 (1H, 8), 7 , 43 (1H, d, J = 8.4 Hz), 7.6 (3H, m), 7.78 (1H, dd, J = 8.6, 1.8 Hz), 7.90 (3H,), 8.09 (1H, broad s), 8.28 (2H, s) - -150 3.41 (3H, d, J-1.1 Hz), 3, 71 (1H, s), 3.80 (2H, s), 6.11 (1H, 8), 7.1-7.4 (6H,), 8.88 (1H, s) - -151 3.50 (3H, d, J = 1.0 hz), 3, 58 (3H, s), 3.62 (2H, s), 6.15 (1H, s), 7.14 (1H, d, J = 9, l Hz), 7.2-7.4 (6H,) - -152 3.58 (3H, e), 3, 90 (3H, e), 4.14 (3H, s), 6.25 (1H, s), 7.21 (1H, d, J = 9.0 Hz), 7.26 (1H, s), 7.44 (1H, m), 7.55 (1H,), 7.76 (1H,), 7.85 (1H, m), 8.58 (1H, s), 10.10 (1H, s) - -153 3.57 (3H, s), 3.91 (3H, s), 4.10 (3H, e), 6.22 (1H, s), 7.22 (1H, d, J = 9.0 Hz), 7.23 (1H, s), 7.64 (2H,), 7.91 (1H, m), 7.99 (1H , d, J = 8.7 Hz), 8.22 (1H, m), 10, 20 (1H, s) - -154 3.56 (3H, s), 3.87 (3H, 8), 4 , 55 (2H, s), 6.27 (1H, S), 6.82 (1H, d, J = 8.8 Hz), 7.21 (2H, m), 7.44 (1H, e), 8.72 (1H, 8) - -155 2, 52 (3H, s), 3.56 (3H, e), 3.90 (3H, s), 6.31 (1H, s), 7.20 (1H, d, J = 9.0 Hz), 7.55 (2H, Itl), 7.81 (4H, m), 10.15 (1H, e) - -156 2.55 (3H, e), 3.52 (3H, s), 3.83 (3H, s), 6.22 (1H, 8), 7.20 (1H, d, J = 9.0 Hz), 7.41 (1H,), 7.66 (1H, s), 7.79 (3H, m), 8.15 (1H , s), 8.26 (1H, s) - -157 3.58 (3H, S), 3.94 (3H, S), 6.35 (1H, S), 7.25 (1H, d, J = 9.0 Hz), 7.61 (2H, m), 7.78 (2H, e), 7.92 (2H, m), 8.04 (1H, s) - -158 3.55 ( 3H, s), 3.84 (3H, s), 6.24 (1H, s), 7.22 (1H, d, J = 9.0 Hz), 7.42 (1H, m), 7, 90 (3H,), 8.14 (1H, s), 8.32 (2H,) - -159 3.56 (3H, s), 3.96 (3H, s), 6.35 (1H, e) ), 7.13 (1H, d, J = 9.0 Hz), 7.70 (6H, m), 8.15 (1H, s) - -160 3.55 (3H, s), 6.24 (1H, e), 7.22 (1H, d, J = 9, 0 HZ), 7.74 t (4H,), 7.92 (4H, m), 8.10 (4H, m) - - 161 3.55 (3H, s), 3.86 (3H, s), 6.25 (1H, s), 7.23 (2H, m), 7.57 (1H, m), 7.72 ( 1H, m), 7.91 (2H,), 8.18 (1H, s) - -162 3.55 (3H, s), 3.85 (3H, e), 6.24 (1H, s), 7.23 (1H, d, 3 = 9.0 Hz) , 7.49 (1H, m), 7.69 (1H,), 7.90 (3H, m), 8.13 (1H, sm), 8.34 (2H, m) - -163 3.56 (3H, s), 3.86 (3H, 8), 6.25 (1H, s), 7.25 (1H, d, ü '= 9.0 Hz), 7.66 (1H, m), 8.05 (3H, m), 8.19 (1H,), 8.32 (1H, d, J = 8.7 Hz), 8.39 (1H, s) - -164.35 (3H, s), 3.89 (3H, s), 4.10 (2H, 8), 6.3". (1H, s), 7.25 (1H, d, J = 9.0 Hz), 8, 33 (1H, s) - -165 3.10 (2H, e), 3.57 (3H, s), 3.90 (2H, e), 4.11 (3H, 8), 6.30 (1H, e), 7.20 (1H, d, J = 9.0 Hz), 7.27 (5H, s), 8.65 (1H, s) - -166 3, 57 (3H, s), 3.90 (5H, s), 4.10 (2H, s), 6.37 [1H, e), 7.25 (1H, d, J = 9.0 Hz), 8.15 (1H, s) - -167 3.50 (3H, s), 3.55 (3H, e), 3.69 (2H, s), 6.16 (1H, s), 7.18 (1H, d, J = 9.0 Hz), 7.28 (5H,), 8.33 (1H, ß) - -168 2.14 (3H, s), 3.20 (3H, s), 3.56 (3H, e), 3.88 (3H, s), 6.29 (1H, s), 7.20 (1H, d, J = 9, 0 Hz), 8.67 (1H, s) ) - -169 3.36 (3H, e), 3.52 (3H, s), 3.79 (2H, m), 5.96 (1H, ß), 7.17 (1H, d, J = 9.0 Hz), 7.49 (3H, m), 7.75 (3H, m), 8.75 (1H, r.) - -170 1.28 (3H, t, J = 7, l Hz ), 3.32 (2H, s), 3.36 (2H, s), 3.55 (3H, e), 3.88 (3H, e), 4.18 (2H, c, J = 7, 1 HZ), 6.30 (1H, s), 7.21 (1H, d, J = 9, 0 Hz), 8.33 (1H, s) - -171 1.26 (3H, t, J = 7, l Hz ), 2.62 (2H, m), 2.85 (2H,), 3.26 (2H, 8), 3.56 (3H, s), 3.88 (3H, s), 4.15 (2H, c, ü '= 7.1 Hz), 6.35 (1H, s), 7.21 (1H, d, J = 9, 0 Hz), 8.66 (1H, s) -172 1.27 (3H, t, J = 7.4 Hz), 2.60 (2H,), 3.27 (2H, s), 3.56 (3H, e) ), 3.88 (3H, e), 6.28 (1H, e), 7.20 (1H, d, J = 9.0 Hz), 8.73 (1H, e) -173 1.28 ( 6H,), 2.97 (1H,), 3.29 (2H, e), 3.57 (3H, e), 3.87 (3H, s), 6.28 (1H, e), 7, 20 (1H, d, J = 9, 0 Hz), 8.79 (1H, e) 2-174 0.99 (3H, m), 1.60 (2H,), 2.53 (2H,), 3.25 (2H, s), 3.57 (3H, s), 3.90 (3H, s), 6.28 (1H, s), 7.20 (1H, d, J = 9.0 Hz ), 8.80 (1H, e) 2-175 3.53 (3H, c, J = 3.9 Hz), 3.79 (3H, 8), 6.30 (1H, s), 6.90 (1H, d, J = 15.7 Hz), 7.36 (3H, m), 7.53 (4H, m), 9.84 (1H, s) 2-176 3.41 (3H, s) ), 3.79 (3H, s), 6.23 (1H, 8), 7.58 (1H, d, J = 8.5 Hz), 6.84 (1H, d, J = 15.6 Hz ), 6.90 (1H, d, J = 15.6 Hz), 7.35 (6H, m), 7.50 (4H, m), 7.79 (1H, d, J = 15.6 Hz ), 7.82 (1H, d, J = 15.6 Hz) 2-177 3.50 (3H, s), 3.79 (3H, e), 6.23 (1H, e), 7.30 (1H, d, J = 8.7 Hz), 7.56 (2H,), 7.85 (4H, m), 8.31 (1H, s), 8.40 (1H, s) 2-178 3.21 (3H, s), 3.88 (3H, s), 6.04 (1H, s), 7.59 (5H,), 7.87 (8H, m), 8.50 (1H, e), 8.57 (1H, s) 2-179 3.57 (3H, S), 4.03 (3H, e), 6.29 (1H, e), 6.52 (1H, d, J = 15.6 Hz), 7.28 (1H, d, J = 8.4 Hz), 7.38 (3H, m), 7.47 (2H, m), 7.62 (1H, d, J = 15.6 Hz), 7.80 (1H, s) 2-180 3.50 (3H, e), 4.00 (3H, e), 6.22 (1H, s), 7.27 (1H, d, J = 8.5 Hz ), 7.59 (2H, m), 7.87 (4H, m), 8.32 (1H, s), 8.38 (1H, s) 2-181 3.52 (3H, e), 3.80 (3H, e), 6.23 (1H, e), 7.17 (1H, d, J = 9, l Hz), 7.58 (2H, m), 7.87 (4H, m ), 8.26 (1H, d, J = 55.6 Hz), 8.31 (1H, 8) - 191 1.27 (3H, t, J7, Hz), 1.29 (3H, t , J = 7, 1 Hz), 1.69 (3H, d, J = 7.0 Hz), 1.70 (3H, d, 3 = 1.0 Hz), 3.56 (3H, s), 3.63 (3H, s), 4.25 (4H,), 4.95 (2H, m), 6.12 (1H, s), 6.41 (1H, s), 7.19 (2H, d, J = 8.9 Hz), 7.56 (4H, m), 7.95 (8H,), 8.54 (1H, s), 8.69 (1H, s), 10.41 (1H , s), 10.65 (1H, s) -192 4.95 (2H, s), 6.23 (1H, e), 7.25 (1H, d, J = 10.0 Hz), 7 , 59 (2H, m), 7.87 (4H, e), 8.27 (1H,), 9.28 (1H, e) - 193 3.56 (3H, c, J = 0.5 Hz ), 6.40 (1H, s), 7.16 (1H, dd, J = 8.7, 2.6 Hz), 7.34 (1H, d, J = 8.7 Hz), 7.5 -7.7 (3H, m), 7.7-8.0 (6H , m), 8.10 (1H, dd, J = 8.6, 1.6 Hz), 8.18 (1H, broad d), 8.27 (1H, broad s) -194 3.53 ( 3H, c, J = 0.8 Hz), 6.36 (1H, s), 7.25 (1H, d, J = 9, l Hz), 7.60 (2H, m), 7.76 ( 1H, dd, J = 8.7, 1.8 Hz), 7.90 (3H, m), 8.21 (1H, s), 8.33 (1H, d, J = 1.5 Hz) - -195 2.45 (1H, d, J = 2.4 Hz), 3.55 (3H, c, J = 0.8 Hz), 4.77 (2H, dd, J = 6, 1, 2, 4 Hz), 6.23 (1H, s), 7.23 (1H, d, J = 9.0 Hz), 7.59 (2H,), 7.90 (4H, m), 8.32 (1H, d, J = 0.7 Hz), 8.36 ( 1H, s) -196 1.28 (3H, t, J = 9.0 Hz), 3.51 (3H, c, J = 0.5 Hz), 4.05 (2H, c, J = 7, l Hz), 6.25 (1H, s), 7.57 (2H, m), 7.88 (4H,), 8.31 (1H, s), 8.38 (1H, s) -197 1 , 20 (3H, t, J = 6.2 Hz), 1.29 (3H, t, J = 6, 2 Hz), 3.54 (3H, c, J = 0.6 Hz), 4.43 (1H, c, J = 6.2 Hz), 6.23 (1H, e), 7.59 (2H,), 7.80 (1H, m), 7.90 (3H, e), 8, 20 (1H, s), 8.30 (1H, e) -198.89 (3H, t), 1.25 (4H, m), 1.53 (2H, m), 2.23 (2H, m), 3.56 (3H, c, J = 0.9 Hz), 3.83 (3H, e), 6.30 (1H, s), 7.20 (1H, d, J = 9, 0 Hz), 7.58 (1H, broad s) -199 3.54 (3H, c, J = 0.7 Hz), 6.29 (1H, s), 6.73 (1H, dd, J = 8, 3, 4, 5 Hz), 7.43 (1H, d, J = 9.9 Hz), 7.57 (2H, m), 7.86 (5H, m), 8.21 ( 1H, dd, J = 8.3, 1.7 Hz), 8.37 (1H, dd, J = 4.5, 1.7 Hz), 8.45 (1H, broad s) -200 3.52 (3H, c, J = 1.0 Hz), 4.82 (2H, d, J = 1.5 Hz), 6.26 (1H, 8), 7.31 (1H, d, J = 8.8 Hz), 7.59 (2H, m), 7.93 (5H, m), 8.35 (1H, d, J = l, 1 Hz) -201 2.43 (3H, s), 3.54 (3H, c, J = 0.9 Hz), 6.36 (1H, e), 7.18 (2H, m), 7.59 (2H, m), 7.8 (6H, m), 8.28 (1H, s) -202 3.51 (3H, e), 3.87 (3H, 8), 6.24 (1H, s), 7.12 (1H, d, > J = 8.8 Hz ), 7.42 ΔIH, d, J = 8.8 Hz), 7.59 (2H, m), 7.81 (1H, m), 7.91 (3H, m), 8.06 (1H, e) , 8.31 (1H, s) -203 3.53 (3H, e), 6.34 (1H, s), 7.17 (1H, m), 7.26 (1H,), 7.57 ( 2H, m), 7.73 (1H, 2d, J = 1, 6, 8.6 Hz), 7.88 (4H, m), 8.18 (1H, s), 8.23 (1H, s) ) --204 0.78 (2H, m), 0.97 (2H,), 1.4 (1H, m), 3.55 (3H, e), 6.34 (1H, s), 7, 12 (1H,), 7.24 (1H, m), 7.43 (1H, m), 7.85 (1H, broad) -205.33 (3H, s), 6.22 (1H, s), 7.24 (1H, d, J = 8.4 Hz), 7.41 (2H, m), 7.65 (4H, m), 7.86 (1H, 2d, 3 = 2.0) , 8.4 Hz), 8.0-8.2 (4H,), 8.55 (1H, s) -206 0.76-0.93 (4H,), 1.50 (1H, m) , 3.55 (3H, e), 3.85 (3H, e), 6.31 (1H, s), 7.19 (1H, d, J = 8.9 Hz), 7.6 (1H, width) - 207 3.44 (3H, s), 3.82 (3H, s), 6.24 (1H, e), 7.32 (1H, d, J = 8.3 Hz), 7, 48 (2H,), 7.6-7.8 (5H,), 8.10 (1H, e), 8.23 (1H, 8), 8.78 (1H, 8) - 1.74 (3H, d, J = 4.7 Hz), 2.76 (3H, d, J = 4.7 Hz), 3.53 (3H, broad c, J = 1, 3 Hz), 3.83 ( 3H, s), 6.3 (1H, 8), 6.66 (1H,), 7.35 (1H, m), 7.39 (1H, d, J = 8.8 Hz) 2 0.76 (3H, t, J = 7.4 Hz), 1.28 (2H, m), 2.96 (2H, m), 3.57 (3H, s), 3.84 (3H, s), 5 , 22 (1H, m), 6.33 (1H, s), 6.70 (1H, s), 7.14 (1H, d, J = 9, 0 Hz) -3 1.22 (12H,), 3.54 (3H, broad s), 3.83 (3H, e), 3.86 (2H, m), 6.25 (1H, s), 6.45 (1H, s), 7.04 (1H, d, J = 9, l Hz) -4 3.52 (3H, e), 3.76 (3H, s), 6.30 (1H, s), 6.90-7.25 (6H, m), 7.37 (1H, s), 7.61 (1H, s) ) -6 3.46 (3H, s), 3.77 (3H, 8), 4.19 (2H, m), 5.75 (1H, m), 6.19 (1H, s), 6, 90-7.30 (7H,) -7 (rotamer mixture) 1.16 (3H, d, J = 6.8 Hz), 1.23 (3H, d, J = 6.8 Hz), 3.47 (3H, s), 3.53 (3H, e), 3.77 (6H, s), 4.72 (2H, m), 5.72 (2H,), 6.11 (1H, s), 6.33 (1H, s), 6.95-7.35 (14H, m) -8 2.99 (3H, s), 3.55 (3H, s), 3.63 (3H, s), 4.38 (1H, d, J = 16.2 Hz), 6.27 (1H, s), 6.58 (1H, s), -,.? l. J.X1, VJ., U 3, J. IiJ, JJ (J ^ l ?, il, /, _> g (3H,) - -9 2.31 (3H, s), 3 , 47 (3H, 8), 3.79 (3H, s), 4.17 (2H,), 5.58 (1H, m), 6.18 (1H, s), 6.74 (1H, e ), 6.90-7.15 (5H,) - -10 (CDCl3 + CD3OD) 3.52 (3H, broad), 3.82 (3H, s), 4.29 (2H, m), 6 , 23 (1H, s), 6.50 (1H, m), 7.70-6.85 (2H, m), 7.14 (1H, d, J = 9.0 Hz), 7.22 ( 1H, m) - -11 2.57 (2H,), 3.21 (2H, m), 3.54 (3H, s), 3.74 (3H, s), 5.51 (1H, m) , 6.27 (1H, e), 7.00-7.30 (5H, m) - -12 (CDCl3 + CD3OD) 1.72 (2H, m), 2.58 (2H,), 3.11 (2H, m), 3.53 (3H, 8), 3.85 (3H, s), 5.78 (1H,), 6.28 (1H, m), 7.05-7.35 (7H , m) - -13 3.55 (3H, 8), 3.81 (3H, s), 6.35 (1H, s), 7.08 (1H,), 7.1 (1H, d, J = 9.00 Hz), 7.25-7.45 (3H, m), 7.55-7.80 (5H, m) 3-23 3.59 (3H, s), 3.64 (3H, e), 4.62 (1H, d, J = 14.8 Hz), 6.33 (1H, s), 6.47 (1H, s), 6.95-7.50 (11H, m) 3 -24 3.40 (3H, s), 3.78 (3H, s), 5.88 (1H, m), 6.12 (1H, s), 7.00-7.30 (12H, m) , s), 6.95-7.50 (11H, m) 3-26 3.56 (3H, s), 3.89 (3H, s), 4.86 (2H, 8), 6.50 ( 1H, e), 6.33 (1H, 8), 7.25 (1H, d, J = 9.0 Hz) 4-1 3.54 (3H, s), 3.64 (3H, e), 3.84 (3H, s), 6.24 (1H, s), 7.25 (1H, s) 4-2 2.87 (3H, e), 2.96 (3H, s), 3.53 (3H, s), 3.63 (1H, e), 6.85 (1H, d, J = 8.9 Hz ) 4-3 3.51 (3H, d, J = 1.0 Hz), 3.95 (3H, s), 6.35 (1H, S), 6.81 (1H, e wide), 7.03 (2H, m), 7.22 (1H, d, J = 9.0 Hz), 7.23 (1H, m), 7.34 (2H,) 4- -4.22 (6H, 8), 3.50 (3H, d, J = 0.5 Hz) , 3.94 (3H, s), 6.35 (1H, s), 6.72 (1H, dd, J = 8.2, 2.5 Hz), 6.77 (1H, d, J = 2 , 5 Hz), 6.84 (1H, broad s), 7.07 (1H, d, J = 8.2 Hz), 7.20 (1H, d, J = 9, 0 Hz) 4-5 3.49 (1H, d, J = 1.0 Hz), 3.83 (3H, s), 5.05 (1H, d, 3 = 12.3 Hz), 5.12 (1H, d, J = 12.3 Hz), 6.20 (1H, s), 6.68 (e wide), 7.15 (1H, d, J = 9, 0 Hz), 7.26-7.37 (5H, m) 4-7 7.50 (3H, broad s), 3.82 (3H, s), 5.01 (1H, d, J = 12.2 Hz), 5.07 (1H, d, J) = 12.2 Hz), 6.20 (1H, s), 6.69 (1H, broad s), 7.02 (2H, irt), 7.17 (1H, d, J = 9.0 Hz) , 7.28 (2H, m) 4-10 3.48 (3H, broad s), 3.99 (3H, s), 6.37 (1H, s), 6.98 (1H, broad s, 7.14 (1H, dd, J = 8.9, 2.3 Hz), 7.24 (1H, d, J = 9.0 Hz), 7.43-7.51 (3H, m), 7 , 37 (7.84 (3H, m) 4-1111.20-1.85 (10H,), 3.56 (3H, broad s), 3.86 (3H, s), 4.57 ( 1H, m), 6.32 (1H, s), 6.53 (1H, s), 7.17 (1H, d, J = 9.0 Hz) -13 3.54 (3H, d, J = l, l Hz), 3.78 (3H, s), 6.33 (1H, s), 7.15 (1H, broad s), 7, 17 (1H, d, J = 9.0 Hz), 7.43-7.52 (5H, m) -23 3.50 (3H, S), 4 , 75 (2H, m), 5.13 (2H,), 6.24 (1H, s), 6.54 (1H, 8), 7.25 (1H, d, J = 8.7 Hz), 7.35 (5H, m) 4-24 3.57 (3H, s), 3.86 (3H, s), 5.37 (2H,), 6.30 (1H, 8), 6.70 ( 1H, s), 7.16 (1H, d, J = 9.0 Hz), 7.20-7.40 (3H,) 4-25 2.06 (6H, e), 2.25 (3H, s), 3.52 (3H, s), 3.94 (3H, s), 6.32 (1H, s), 6.83 (2H, s), 7.09 (1H, e wide), 7 , 20 (1H, d, J = 9.0 Hz) 4-26 2.25 (6H, 8), 3.51 (3H, s), 3.83 (3H, 8), 5.01 (2H, m), 6.21 (1H, e), 6.65 (1H, broad s), 7.00-7.20 (4H, m) 4-27 1.30 (9H, 8), 3.50 ( 3H, s), 3.96 (3H, 8), 6.32 (1H, s), 6.84 (1H,), 7.10-7.40 (5H,) 4-28, 3.43 (3H , s), 3.82 (3H, s), 5.25 (2H, m), 6.12 (1H, e), 6.73 (1H, e wide), 7.16 (1H, d, J = 9, 0 Hz), 7.30-7.55 (3H,), 7.70-7.85 (4H,) 4-29 3.57 (3H, s), 3.85 (3H, s) , 5.17 (1H, d, J = 11, 9 Hz), 5.27 (1H, d, J = 11, 9 Hz), 6.28 (1H, e), 6.64 (1H, broad s) ), 6.92 (2H,), 7.17 (1H, d, J = 9.0 Hz), 7.34 (1H, m) 4-30 3.49 (3H, s), 3.84 ( 3H, 8), 4.99 (1H , d, J = 12.6 Hz), 5.06 (1H, d, J = 12.6 Hz), 6.23 (1H, s), 6.64 (1H, broad s), 7.00- 7.25 (4H, m) 4-31 1.23 (3H, t, J = 7.6 Hz), 2.64 (2H, J = 7.6 Hz) 3.50 (3H, d, J = 0.9), 3.83 (3H, e), 5.02 (1H, d, J = 12, l), 5.08 (1H, d, J = 12, l Hz), 6.22 (1H , e), 6.67 (1H, broad s), 7.10-7.30 (5H, m) 4-32 3.52 (3H, s), 3.85 (3H, e), 5.03 (2H,), 6.24 (1H, e), 6.64 (1H, e wide), 7.10-7.21 (2H,), 7.38-7.44 (2H, m) -33 3.52 (3H, d, J = 0.8 Hz), 3.86 (3H, s), 5.22 (1H, d, J = 13.2 Hz), 5.31 (1H, d, J = 13.2), 6.22 (1H, s), 6.71 (1H, broad s), 7.18 (1H, d, J = 9, 0 Hz), 7.70-7.60 (3H ,), 7.68 (1H, m) -34 3.54 (3H, e), 3.88 (3H, e), 5.49 (2H, e), 6.28 (1H, e), 7 , 24 (1H, d, J = 9.0 Hz), 7.45-7.70 (3H, m), 8.09 (1H, m) -35 3.53 (3H, s), 3.83 (3H, s), 3.84 (3H, s), 5.12 (1H, d, J = 12.5 H2), 5.18 (1H, d, J = 12.5), 6.24 ( 1H, s), 6.72 (1H, e wide), 6.80-6.95 (2H,), 7.15 (1H, d, J = 9.0 Hz), 7.20-7.40 (2H, m) -36 3.51 (3H, d, J = 1.0 Hz), 3.87 (3H, s), 5.17 (1H, d, J = 13.5 Hz), 5, 24 (1H, d, J = 13.5), 6.24 ( 1H, s), 6.89 (1H, broad s), 7.18 (1H, d, J = 9, 0 Hz), 7.20-7.29 (2H, m), 7.68 (1H, m), 8, 58 (1H, m) - -37 2.31 (6H, 8), 3.52 (3H, s), 3.84 (3H, 8), 5.01 (2H, m), 6.23 (1H , s), 6.65 (1H, broad s), 6.92 (2H, e wide), 6.96 (1H, broad s), 7.16 (1H, d, J = 9.0 Hz) - -38 2.25 (3H, s), 2.35 (3H, 8), 3.53 (3H, d, J = 0.9 Hz), (2H, m), 6.23 (1H, e) , 6.65 (1H, e wide), 6.92 (2H, e wide), 6.96 (1H, broad s), 7.16 (1H, d, J = 9.0 Hz) - -39 3 , 53 (3H, e wide), 3.86 (3H, e), 5.14 (2H,), 6.27 (1H, e), 6.70 (1H, broad s), 6.90-7 , 10 (3H, m), 7.19 (1H, d, J = 9.0 Hz) - -40 3.51 (3H, d, J = C, 9 Hz), 3.81 (3H, s) , 3.82 (3H, s), 4.98 (1H, d, J = 12.0 Hz), 5.05 (1H, d, J = 12, 0 Hz), 6.22 (1H, e) , 6.63 (1H, broad s), 6.87 (2H, m), 7.16 (1H, d, J = 9.0 Hz), 7.25 (2H, m) - -41 3.53 (3H, d, J = 0.9 Hz), 3.83 (3H, s), 4.95 (1H, d, J = 12, l Hz), 5.01 (1H, d, J = 12, l Hz), 5.96 (2H, s), 6.25 (1H, s), 6.63 (1H, broad s), 6.78 (3H, m), 7.17 (1H, d, J = 9.0 Hz) - 42 1.24 (6H, d, J = 6.9 Hz), 2.91 (1H, e), 3, 50 (3H, d, J = 0.9 Hz), 3.82 (3H, e), 5.02 (1H, d, J = 12, l Hz), 5.08 (1H, d, J = 12, l Hz), 6.23 (1H, s), 6.70 (1H, e wide), 7.15 (1H, d, J = 9, 0 Hz), 7.22 (4H, m) - -43 3.48 (3H, d, J = 1.0 Hz), 3.85 (3H, s), 5.10 (1H, d, J = 13.0 Hz), 5.18 (1H, d , J = 13.0 Hz), 6.18 (1H, e), 6.72 (1H, 8 broad), 7.18 (1H, d, J = 9.0 Hz), 7.41 (2H, m), 7.60 (2H,) --44 3.50 (3H, d, J = 1.0 Hz), 3.85 (3H, e), 5.05 (1H, d, J = 12, 8 Hz), 5.12 (1H, d, J = 12.8 Hz), 6.22 (1H, s), 6.68 (1H, 8 wide), 6.95-7.10 (3H,) , 7.18 (1H, d, J = 9.0 Hz), 7.30 (1H, m) --45.49 (3H, d, J = 0.9 Hz), 3.82 (3H, s), 5.05 (1H, d, J = 12.6 Hz), 5.11 (1H, d, 3 = 12, 6 Hz), 6.21 (1H, s), 6.79 (1H, s wide), 7.10-7.20 (3H,), 7.31-7.36 (2H, m) - 46 0.89 (4H, 8 wide), 3.54 (3H, d, J = 1.0 Hz), 3.75 (3H, s), 4.15 (2H,), 6.28 (1H, e), 6.56 (1H, broad s), 7.15 (1H, d) , J = 9.0 Hz) --47 1.50 (3H, d, J = 6.6 Hz), 3.48 (3H, s), 3.84 (3H, 8), 5.69 (1H , c, J = 6.6 Hz), 5.97 (1H, s), 6.73 (1H, broad s), 7.14 (1H, d, J = 9, 0 Hz), 7.20- 7.40 (5H, m) --48 3 , 57 (3H, d, J = 0.9 Hz), 3.86 (3H, s), 5.19 (1H, d, J = 12.3 Hz), 5.25 (1H, d, J = 12.3 Hz), 6.31 (1H, s), 6.61 (1H, broad s), 7.20 (1H, d, J = 9.0 Hz) --49 3.52 (3H, d , J = 0.9 Hz), 5.22 (2H, 8), 6.33 (1H, s), 6.53 (1H, e wide), 7.00-7.45 (7H,) - 50 3.54 (3H, e), 6.36 (1H, e), 6.84 (1H, e wide), 7.00-7.45 (8H, m) -51 2.20 (3H, 8), 3.45 (3H, d, J = 0.8 Hz), 5.10 (2H, m), 6.22 (1H, s), 6.90-7.10 (2H, m), 7.15-7.27 (3H, m), -52 2.42 (3H, 8), 3.52 (3H, s), 6.37 (1H, s), 7.00- 7.40 (6H, m) -53.21 (6H, e), 3.50 (3H, broad d J = 0.5 Hz), 3.94 (3H, s), 6.35 (1H, s), 6.73 (2H, m), 6.84 (1H, e wide), 7.07 (1H, d, J = 8, l Hz), 7.20 (1H, d, J = 9.0 Hz) -54 3.53 (3H, broad d, J = 1, Hz), 3.85 (3H, s), 5.16 (1H, d, J = 12.9 Hz), 5.25 (1H, d, J = 12, 9 Hz), 6.24 (1H, s), 6.71 (1H, e wide), 7.18 (1H, d, J = 9, 0 HZ), 7.2-7 , 4 (4H,) -55 2.11 (6H, s), 3.52 (3H, 8), 3.95 (3H, s), 6.33 (1H, s), 7.03 (3H, s wide), 7.08 (1H, broad s), 7.22 (1H, d, J = 9.0 Hz) -56 3.51 (3H, broad d, J = l, l Hz), 3, 83 (3H, e), 5.07 (1H, d, J = 12.3 Hz), 5.14 (1H, d, J = 12.3 Hz), 6.23 (1H, s), 6, 68 (1H, broad s), 7.1-7.3 (4H, m) -57 2.88 (2H, t, J = 6.5 Hz), 3.55 (3H, s), 3.77 (3H, s), 4.25 (2H, t, J = 6.5 Hz), 6.29 (1H, s), 6.52 (1H, broad s), 7.1-7.4 (6H ,) -58 3.52 (3H, broad d, J = 1.0 Hz), 3.83 (3H, s), 3.84 (3H, 8), 5.12 (1H, d, J = 12 , 5 Hz), 5.17 (1H, d, J = 12.5 Hz), 6.24 (1H, e), 6.71 (1H, e wide), 6.90 (2H, s), 7 , 15 (1H, d, J = 9.0 Hz), 7.2-7.3 (4H,) -59 3.50 (3H, e), 3.74 (6H, s), 6.32 ( 1H, s), 6.56 (2H, width), 7.18 (1H, d, J = 9, 0 Hz) -60 2.34 (3H, s), 3.50 (3H, broad d, J = 1, Hz), 3.83 ( 3H, e), 5.00 (1H, d, J = 12, l Hz), 5.07 (1H, d, J = 12.1 Hz), 6.20 (1H, s), 6.64 (1H, broad s), 7.1-7.2 (5H,) -61 3.50 (3H, broad d, J = 1 , 0 Hz), 3.83 (3H, s), 5.01 (1H, d, J = 12.5 Hz), 5.07 (1H, d, J = 12.5 Hz), 6.20 (1H, s), 6.66 (1H, broad s), 7.17 (1H, d, J = 9, 0 Hz), 7.2-7.3 (4H, m) - • 62 3.53 (3H, broad d, J = 1.0 Hz), 3.85 (3H, 8), 5.12 (1H, d, J = 13.0 Hz), 5.20 (1H, d, J = 13 , 0 Hz), 6.25 (1H, s), 6.67 (1H, broad s), 7.19 (1H, d, J = 9.0 Hz), 7.2-7.3 (4H, m), 7.41 (1H, d, 3 = 9, 0 Hz) --63.53 (3H, broad d, J = 1.0 Hz), 3.83 (3H, e), 3.88 (3H, s), 3.89 (3H, s), 4.99 (1H, d, J = 12.0 Hz), 5.04 (1H, d, J = 12.0 Hz), 6.20 (1H, s), 6.59 (1H, broad s), 6.8-6.9 (3H, m), 7.16 (1H, d, J = 9, 0 Hz) 4--64 3.51 (3H, broad d, J = 0.9 Hz), 3.86 (3H, e), 5.15 (1H, d, J = 13.5 Hz), 5.21 ( 1H, d, J = 13.5 Hz), 6.21 (1H, s), 6.68 (1H, broad s), 7.21 (1H, d, J = 9, 0 Hz), 7.46 (2H, d, J = 8.7 Hz), 8.21 (2H, d, J = 8.7 Hz) 4--65 3.50 (3H, broad d, J = 1.0 Hz), 3.81 (3H, s), 3.85 (3H, s), 5.02 (1H, d, J = 12 , 5 Hz), 5.10 (1H, d, J = 12.5 Hz), 6.21 (1H, s), 6.67 (1H, broad s), 6.8-6.9 (3H, m), 7.17 (1H, d, J = 9.0 Hz), 7.25 (1H, t, J = 7.7 Hz) 4--66 3.53 (3H, broad d, J = 0 , 9 Hz), 3.82 (3H, s), 4.11 (2H, e), 6.29 (1H, e), 7.04 (1H, broad s), 7.20 (1H, d, J = 9.0 Hz), 7.25 (5H,) 4--67 3.52 (3H, broad d, J = 1.0 Hz), 3.86 (3H, e), 5.17 (1H , d, J = 13.2 Hz), 5.21 (1H, d, J = 13.2 Hz), 6.24 (1H, s), 6.65 (1H, e wide), 7.20 ( 1H, d, J = 9.0 Hz), 7.53 (1H, t, J = 8.0 Hz), 7.63 (1H, d, J = 8.0), 8.18 (2H,) 4--68 2.35 (3H, e), 3.50 (3H, broad d, J = 1.0 Hz), 3.83 (3H, s), 5.02 (1H, d, J = 12 , 2 Hz), 5.10 (1H, d, J = 12.2 HZ), 6.22 (1H, e), 6.65 (1H, broad s), 7.1-7.3 (5H, m) 4--69.27 (3H, e), 2.30 (6H, H), 3.54 (3H, broad d, J = 1.1 Hz), 3.83 (3H, s), 5.10 (1H, d, J = ll, 8 Hz), 5.16 (1H, d, J = ll, 8 Hz), 6.25 (1H, s), 6.63 (1H, e wide) , 6.87 (1H, d, J = 9, 0 Hz) -70 3.55 (3H, broad d, J = 1, Hz), 3.83 (3H, s), 4, 99 (1H, d, J = 13, l Hz), 5.08 (1H, d, J = 13, l Hz), 6.27 (1H, s), 6.35 (2H, m), 6, 63 (1H, e wide), 7.17 (1H, d, J = 9.0 Hz), 7.41 (1H,) -1.02 (1H, broad s), 4.05 (3H, s) ), 7.66 (1H, d, 3 = 8.8 Hz) 5-2 4.36 (2H, e wide), 7.61 (1H, d, J = 8.7 Hz) 5-3 2, 30 (2H, td, J = 27.2, 5.6 Hz), 3.85 (3H, s), 4.22 (2H, t, J = 6.8 Hz), 4.42 (2H, 8) width), 4.60 (2H, td, J = 46.9, 5.6 Hz), 6.65 (1H, d, J = 9, 5 Hz) 5-4 2.24 (2H, td, J = 26.7, 5.7 Hz), 4.19 (2H, t, J = 6.9 Hz), 4.61 (2H, td, J = 47.0, 5.7 Hz), 7.86 (1H, d, J = 9.0 Hz) 5-5 2,, 30 (2H, td, J = 26.4, 5.7 Hz), 4.17 (2H, t, J = 6.8 Hz ), 4.55 (2H, td, J = 47.0, 5.7 Hz), 4.88 (2H, broad s), 6.55 (1H, d, J = 9.6 Hz), 8, 07 (1H, wide) -6 4.06 (3H, 8), 7.87 (1H, s) 5-7 2.13 (2H, m), 3.06 (3H, s), 3.93 (2H, t, J = 4, 8 Hz), 4.60 (2H, broad d, J = 47.0), 7.53 (1H, s) 5-8 2.30 (2H, td, 3 = 26, A, 5, 6 Hz), 4.24 (2H, t, J = 6.7 Hz), 4.58 (2H, td, J = 46.8, 5.6 Hz), 7.87 (1H, e), 9 , 62 (1H, 8) 5-9 2.06 (1H, s), 2.30 (2H, tdt, 3 = 21, 1, 6.8, 5.4 Hz), 4.24 (2H, t , J = 6.8 Hz), 4.60 (2H, td, J = 49.6, 5.4 Hz), 5.90 (2H, e), 6.77 (1H, s) 5-15 2 , 30 (2H, tdt, J = 26.0, 6.1, 5.5 Hz), 2.62 < 1H, d, J = 2.4 Hz), 4.21 (2H, t, J = 6.8 Hz), 4.48 (2H, s), 4.60 (2H, td, J = 46.9 , 5.5 Hz), 4.73 (2H, d, 3 = 2, 4 Hz), 6.92 (1H, s), 5-16, 1.35 (6H, d, J = 6.2 Hz), 2.29 (2H, tdt, 3 = 21, 1, 5.9, 5.5 Hz), 4.21 (2H, t, J = 6.8 Hz), 4.29 (2H, e wide), 4.53 (1H, c, J = 6.2 Hz), 4.59 (2H, td, J = 46.9, 5.5 Hz), 6.92 (1H, s) 5--17 2, 30 (2H, td, J = 26.4, 5.7 Hz), 2.75 (1H, t, 3 = 2.5 Hz), 4.19 (2H, t, J = 6.8 Hz), 4.61 (2H, td, J = 47.0, 5.7 Hz), 4.72 (2H, d, 3 = 2.5 Hz), 5.02 (2H, broad s), 6.61 ( 1H, d, J = 9.4 Hz) 5--18 1.35 (6H, d, J = 6.0 Hz), 2.30 (2H, tdt, J = 26.9, 6.8, 5 , 4 Hz), 4.21 (2H, t, J = 6.8 Hz), 4.37 (2H, 8 wide), 4.52 (1H, penta, J = 6.0 Hz), 4.59 (2H, td, J = 46.5, 5.4 Hz), 6.65 (1H, d, 3 = 9, 6 Hz) 5--26 2.08 (2H, m), 3.84 (3H , s), 4.09 (2H, t, J = 6.7 Hz), 4.31 (2H, td, J = 46.9, 5.6 Hz), 7.26 (1H, d, J = 9, 1 Hz), 7.55 (2H, m), 7.89 (4H, m), 8.40 (1H, e), 8.53 (1H, broad s) 5--27 1.67 (2H, td, J = 26.5, 5.8 Hz), 3.86 ( 3H, s), 3.89 (2H, s), 3.97 (2H, td, J = 42.4, 5.6 Hz), 7.27 (1H, d, J = 8.7 Hz), 7.52 (4H,), 7.78 (4H, m), 7.88 (4H, m), 8.54 (2H, e) 5--28.22 (2H, td, J = 26, 2, 5.8 Hz), 3.81 (3H, e), 4.01 (2H, e), 4.13 (2H, d, J = 6.8 Hz), 4.52 (2H, td, J = 46.9, 5.6 Hz), 4.64 (2H, s), 7.23 (1H, d, J = 9, l Hz), 7.36 (5H,), 8.67 (1H , s wide) 6--1 2.48 (3H, e), 7.03 (1H, t, J = 57.9 Hz), 7.65 (1H, d, J = 8.6 Hz), 9 , 88 (1H, s) 6--2 2.48 (3H, e), 4.25 (2H, broad s), 5.70 (1H, e wide), 6.59 (1H, d, J = 9.4 Hz), 7.07 (1H, t, J = 58.0 Hz) 6--13 2.53 (3H, s), 6.89 (1H, ddd, J = 12, 5, 8, 3, 2.4 Hz), 7.05 (1H, m), 7.10 (1H, t, J = 58.0 Hz), 7.33 (1H, d, J = 2.2 HZ), 8 , 21 (1H, ddd, J = 9, 1, 9.1, 6.5 Hz), 8.57 (1H, d, J = 2.2 Hz), 8.72 (1H, broad d, J = 16.5 Hz) 6--14 2.37 (3H, s), 3.88 (3H, s), 6.94 (1H, ddd, J = 10.9, 8.3, 2.3 Hz) , 6.99 (1H,), 7.05 (1H, t, J = 58.0, Hz), 7.26 (1H, d, J = 9, l Hz), 8.04 (1H, ddd, J = 8.8, 8.8, 6.5 Hz), 8.48 (1H, broad d, J = 13.4 Hz) - 15 2.31 (3H, e), 3.88 (3H, e), 7.03 (1H, t, J = 58.8 Hz), 7.25 (1H, d, J = 9.4 Hz), 7.60 (2H, m), 7.8-8.0 (4H, m), 8.25 (1H, e), 8.40 (1H, e) - • 16 2.54 (3H, e), 7.12 (1H, d, J = 58.0 Hz), 7.35 (1H, d, J = 2 , 3 Hz), 7.61 (2H,), 7.83 (1H, dd, J = 8.5, 1.8 Hz), 7.90 (3H,), 8.29 (1H, s), 8.48 (1H, d, 3 = 2, 3 Hz), 8.64 (1H, broad s) - 17.29 (3H, s), 3.89 (3H, e), 7.03 ( 1H, t, J = 58.0 Hz), 7.53 (1H, e), 7.60 (2H, m), 7.92 (4H, m), 8.07 (1H, broad s), 8 , 37 (1H, e wide) --18 1.29 (3H, t, J = 7, l Hz), 2.45 (3H, s), 4.3 (2H, c, J = 7, l Hz ), 6.7 (1H, wide), 7.03 (1H, t, J = 58.0 Hz), 7.83 (1H, e wide) --19 1.27 (3H, t, J = 7 , 0 Hz), 2.48 (3H, s), 4.18 (2H, c, J = 7.0 Hz), 4.51 (2H, s), 6.67 (1H, e), 6, 91 (1H, 8), 7.08 (1H, t, J = 58.0 Hz) - 20 2.38 (3H, s), 4.77 (4H, s), 7.16 (1H, t , 3 = 51, 1 Hz), 7.17 (1H, s) - 21 2.47 (3H, s), 7.04 (1H, t, J = 7.2 Hz), 7.59 (1H , 2d, J = 2.3 Hz, 8.6 Hz), 7.91 (1H, t, J = 2, l Hz) - 22 2.47 (3H, e), 3.65 (2H, s ), 6.75 (1H, 2d, J = 2.2 Hz, 9.4 Hz), 7.07 (1H, t, J = 57, 9 Hz), 7.20 (1H, t, J = 1.8 HZ) - 23.22 (3H , s), 6.9-7.1 (3H,), 7.10 (1H, t, J = 57, 9 Hz), 7.14 (1H, 2d), 8.06 (1H, m), 9.76 (1H, s) - 24 2.51 (3H, e), 6.93 (1H, 2d, 3 = 2, 2 Hz, 8.9 Hz), 7.12 (1H, t, J = 58.0 Hz), 7.12 (1H, s), 7.61 (2H, m), 7.9-8.0 (3H,), 8.07 (1H, 2d, J = l, 7 Hz), 8.68 (1H, s), 9.74 (1H, s), - 4.01 (3H, e), 4.03 (3H, broad c, J = 1, 0 Hz), 7.43 (1H, d, J = 8.4 Hz) --2 3.84 (3H, s), 4.06 (3H, 8), 4.57 (2H, s), 6.57 (1H , d, J = 9.3 Hz) -3.0 4.07 (3H, broad d, J = 0.9 Hz), 6.61 (1H, d, J = 9.2 Hz) -14 3.87 ( 3H, 8), 3.91 (3H, s), 7.23 (1H, d, J = 8.9 Hz), 7.60 (2H, m), 7.80-7.96 (4H,) , 8,13 (1 H, 8 broad), 8,32 (1 H, broad s) 7-15 3,86 (3 H, s), 3,97 (3 H, e), 6,45 (1 H, d, J = 15.6 Hz), 7.20 (1H, d, J = 8.9 Hz), 7.30-7.52 (6H, m), 7.60 (1H, d, J = 15.6 HZ ) 8-1 1.84 (4H,), 2.44 (4H, m), 7.62 (1H, d, J = 8.5 Hz), 9.88 (1H, broad) 8-2 1, 79 (4H, m), 2.41 (4H, m), 5.53 (3H, broad), 6.53 (1H, d, J = 9, 1 Hz) 8-3 1.81 (4H, m ), 2.43 ( 4H, m), 2.58 (1H, t, J = 2.4 Hz), 4.24 (2H, e wide), 4.69 (2H, t, 3 = 2.4 Hz), 6.60 (1H, d, J = 9.2 Hz) 8-4 1.35 (6H, d, J = 6.2 Hz), 1.82 (4H, m), 2.43 (4H,), 4, 11 (2H, broad s), 4.48 (1H, c, J = 6.2 Hz), 6.60 (1H, d, J = 9.4 Hz) 8-5 1.77 (4H, m) , 1.82 (4H, m), 2.43 (4H, m), 2.34 (4H, m), 4.04 (2H, e wide), 4.79 (1H, m), 6.61 (1H, d, J = 9.4 Hz) 8-6 1.82 (4H, m), 2.42 (4H, ra), 4.03 (2H, e), 7.48 (1H, d, J = 8.6 Hz) 8-7 1.80 (4H, m), 2.08 (2H, e wide), 2.41 (4H, m), 3.83 (3H, e), 6.60 (1H, d, J = 9.4 Hz) 8-8 1.78 (4H, m), 2.38 (4H, m), 3.86 (3H, 8), 6.96 (2H,), 7.25 (1H , d, J = 9.0 Hz), 8.01 (1H, m), 8.19 (1H, d, J = 12.6 Hz) 8-9 1.68 (4H, m), 2.32 (4H, m), 3.82 (3H, s), 7.22 (1H, d, J = 9, l Hz), 7.59 (2H,), 7.91 (5H, m), 8, 34 (1H, 8) - 13 1.76 (4H, m), 2.34 (4H, m), 2.37 (1H, t, J = 2.4 Hz), 4.77 (2H, t , J = 2.4 Hz), 6.95 (2H,), 7.27 (1H, d, J = 8.9 Hz), 8.04 (1H, m), 8.38 (1H, broad d , J = 12.5 HZ) --18 1.28 (6H, d, J = 6.2 Hz), 1.76 (4H, m), 2.32 (4H, m), 4.45 (1H , c, J = 6.2 Hz), 6.95 (2H, m), 7.24 (1H, d, J = 9.0 Hz), 8.00 (1H, m), 8.31 (1H , d wide, J = 12.7 Hz) - 30 1.71 (4H, m), 2.33 (4H, m), 8.30 (3H, s), 5.39 (1H, d, J = 10.9 Hz), 5.86 (1H, d, J = 17.6 Hz), 6.75 (1H, dd, J = 17.6, 10.9 Hz), 7.21 (1H, d , J = 9.0 Hz), 7.47 (2H, d, J = 8.2 Hz), 7.77 (2H, d, J = 8.2 Hz), 7.85 (1H, s) - -31 1.76 (4H, m), 2.38 (4H, m), 3.82 (3H, s), 6.52 (1H, d, J = 15.6 Hz), 7.19 (1H, d, J = 9.0 Hz), 7.37 (3H, m), 7.65 (1H, d, J = 15.6 Hz) - 32 1.85 (4H, m), 2.45 (4H, m), 8.31 (2H, e) --33 1.81 (4H, m), 2.43 (4H, m), 7.37 (1H, d, J = 8.5 Hz), 7.69 (1H, 2d, J = 2.3 Hz, 8.5 Hz), 8.10 (1H, d, J = 2.3 Hz) --34.86 (4H, m), 2.46 (4H, m), 7.72 (1H, d, J = 8, 8 Hz), 8.56 (1H, 2d, J = 2.6 Hz, 8.8 Hz), 8.92 (1H, d, J = 2.6 Hz) - 35 1 , 80 (4H, m), 2.40 (4H, m), 3.83 (2H, s), 6.79 (2H, m), 6.91 (1H, d, J = 8.3 Hz) -36 1.78 (4H, m), 2.40 (4H, m), 7.15-7.30 (2H, m), 7.6 (2H, m), 7.9 (4H,) , 8.14 (1H, d, 3 = 2, 2 Hz), 8.34 (1H, s), 8.59 (1H, s) - 1.91 (4H, m), 3.67 ( 4H, m), 7.65 (1H, d, J = 8.3 Hz) - 3.87 (4H, m), 3.62 (4H, m), 4.03 (3H, 8), 7.53 (1H, d, J = 8.5 Hz) - 4.88 (4H, m), 3.65 (4H, m), 3.85 (3H, s), 4.28 (2H , 8), 6.64 (1H, d, J = 9.5 Hz) -12 2.01 (4H, m), 3.73 (2H, m), 3.92 (1H, m), 4, 15 (1H, m), 7.53 (1H, d, J = 8.5 Hz), 7.76 (1H, J = 8.5, 2.4 hz), 8.21 (1H, d, 3 = 2, 4 Hz) -13 1.90 (4H, m), 3.69 (2H, ra), 3.95 (2H, e), 4.85 (2H, broad s), 6.79 (2H, m), 7.00 (1H, d, J = 8.3 Hz) 9-14 1.94 (4H, m), 3.69 (2H, m), 4.03 (2H, ra), 7.27 (2H, m), 7.59 (2H, m), 7, 94 (4H, m), 8.19 (1H, d, J = 2.0 Hz), 8.47 (1H, s), 9.11 (1H, e wide) 9-15 1.70 (4H, m), 3.50 (4H, m), 3.83 (3H, s), 7.23 (1H, d, J = 9.0 Hz), 7.59 (2H, m), 7.92 ( 4H, m), 8.34 (1H, 8), 8.43 (1H, s) 9-16 1.82 (4H, m), 3.58 (4H, m), 3.87 (3H, s) ), 6.9-7.1 (2H, m), 7.27 (1H, d, J = 9.0 Hz), 8.07 (1H, m), 8.49 (1H, d, J = 13, l Hz) 9-17 1.89 (4H, m), 3.65 (4H, m), 7.53 (1H, d, J = 8.6 Hz), 7.72 (1H, 2d, J = 2.3 Hz, 8.5 Hz), 8.13 (1H, d, J = 2.3 Hz) 9-18 1.85 (4H, m), 3.63 (4H, m), 4 , 03 (2H, e), 6.82 (2H, m), 7.09 (1H, 2d, J = 0.6 Hz, 8.0 Hz) 9-19 1.80 (4H, m), 3 , 60 (4H, m), 7.22 (1H, 2d, J = 2.3 Hz, 8.7 Hz), 7.35 (1H, d, J = 8, 7 Hz), 7.56 (2H , m), 7.89 (4H, m), 8.08 (1H, d, J = 2.3 Hz), 8.43 (1H, s), 9.41 (1H, s) 11-1 4 , 05 (3H, 8), 7.30 (1H, m), 7.53 (1H, d, J = 8, 7 Hz), 8.01 (1H, d, J = 2, l Hz) 11- 2.333 (1H, m), 7.70 (1H, d, 8.4 Hz) 8.06 (1H, d, J = g, J.Iz, u, g, and VJ-1, s 11-3 6.53 ( 1H, d, J = 9.5 Hz), 6.53 (3H, broad), 7.40 (1H, s), 8.17 (1H, s) 11-4 3.86 (3H, s), 4.33 (2H, broad s), 6.65 (1H, d, J = 9.5 Hz), 7.34 (1H, cd, J = 2, 2 Hz, 1.0 Hz), 8.10 (1H, d, J = 2.2 Hz) 1-5.31 (3H , s), 3.79 (3H, s), 4.33 (2H, broad s), 7.21 (1H, d, J = l, l Hz), 7.49 (1H, d, J = 8 , 8 Hz), 7.95 (1H, d, J = 2.2 Hz) 1-6 3.86 (3H, s), 7.26 (1H, d, J = 9, 2 Hz), 7, 27 (1H, cd7 J = 2.2, 1.1 Hz), 7.56 (2H, m), 7.88 (4H, m), 7.97 (1H, d, J = 2.2 Hz) , 8.38 (1H, e), 8.79 (1H, s) 1-7 3.93 (3H, 8), 7.30 (1H, d, J = 8.7 Hz), 7.35 ( 1H, cd, J = 2.2, 1.1 Hz), 8.08 (1H, d, 3 = 2.2 Hz) 11-8 1.20, 1.23 (3H, t, J = 7, l Hz), 3.20 (2H, m), 3.94, (3H, s), 4.16 (2H, c, J = 7, l Hz), 4.52 (1H, m), 7, 32 (2H, m), 8.08 (1H, m) 11-9 2.43 (3H, c, J = 2, l Hz), 7.67 (1H, d, J = 8.5 Hz), 8.01 (1H, s), 10.2 (1H, broad) 11-10 2.46 (3H, c, J = 1, 8 Hz), 2.63 (3H, broad), 6.60 (1H , d, J = 9.4 Hz), 8.08 (1H, e) 11-11 2.45 (3H, c, J = 1, 9 Hz), 3.87 (3H, s), 6.66 (1H, d, J = 9.6 Hz), 8.06 (1H, s) 11-12 2.44 (3H, c, J = 1, 9 Hz), 2.58 (3H, 8), 3 , 84 (3H, s), 6.60 (1H, d, J = 9.4 Hz), 8.03 (1H, 8) 11-13 2.38 (3H, c, J = 1, 8 Hz) 3.88 (3H, s) 7.26 (1H, d, J = 9.3 Hz), 7.59 (2H, m), 7.80 (1H, m), 7.91 (4H, m), 8.11 (1H, s), 8.30 (1H, e) 12-1 1.64 (3H, m), 1.91 (1H, m), 2.10 (1H, m), 2.35 (1H, m), 3.16 (1H, m), 4.17 (1H, m), 4.82 (1H, m), 7.66 (1H, d, J = 8.2 Hz), 10.04 (1H, broad) 12-2 1.61 (3H, m), 1.91 (1H, m), 2.10 (1H, ra) , 2.38 (1H, m), 3.13 (1H, m), 4.11 (1H, m), 4.14 (2H, s), 4.87. (1H, m), 5.49 (1H, e), 6.64 (1H, d, J = 9, 0 Hz) 12-3 1.61 (3H, m), 1.90 (1H, m), 2.08 (1H, m), 2.35 (1H, m), 3.10 (1H, m), 4, 07 (1H, m), 4.2 (2H, wide), 4.88 (1H, m), 5.5 (1H, broad), 6.63 (1H, d, J = 9, 0 Hz) 12-4 1.60 (3H, m), 1.89 (1H, m), 2.09 (1H, m), 2.34 (1H, m), 3.09 (1H, m), 3.85 (3H, e), 4.11 (1H, m), 4.3 (2H, broad), 4.87 (1H, m), 6.63 (1H, d, J = 9, 0 Hz ) 12-5 1.4-1.7 (3H, m), 1.7-2.4 (3H, m), 2.95 (1H, m), 3.85 (3H, s), 3, 97 (1H, m), 4.71 (1H, m), 7.26 (1H, m), 7.60 (2H, m), 7.93 (4H, m), 8.15 (1H, s) ), 8.44 (1H, S) 12-6 1.54 (3H, m), 1.78 (1H, m), 2.07 (1H, m), 2.27 (1H, m), 2 , 95 (1H, m), 4.01 (1H, m), 4.22 (1H, m), 7.44 (1H, d, J = 8.5 Hz), 7.69 (1H, 2d, 3 = 2.3 Hz, 8.5 Hz), 8.11 (1H, d, J = 2.3 Hz) 12-7 1.50 (3H, m), 1.78 (1H, m), 2 , 05 (1H, m), 2.28 (1H, m), 2.89 (1H, ra), 3.90 (1H, ra), 3.95 (2H, e), 4.15 (1H, m), 6.81 (2H, m), 6.99 (1H, d, 3 = 1, 9 Hz) 12-8 1.41 (3H, m), 1.68N (1H, m), 1.93 (1H, m), 2.24 (1H, m), 2.83 (1H, m), 3, 88 (1H, m), 4.11 (1H, m), 7.23 (2H, m), 7.54 (2H, m), 7.87 (4H, m), 7.97 (1H, s) ), 8.38 (1H, s), 9.11 (1H, e) 13-1 3.46 (1H, broad s), 7.61 (1H, d, J = 8.6 Hz), 7, 88 (2H, m), 7.99 (2H, m) 13-2 5.42 (1H, e wide), 6.58 (1H, d, J = 9, 4 Hz), 7.95 (4H, m) 13-3 3.86 (3H, e), 7.28 (1H, d, J = 9.0 Hz), 7.50-7.95 (10H, m), 8.03 (1H, 8 width), 8.28 (1H, broad s) 13-4 3.89 (3H, s), 6.89 (2H, m), 7.30 (1H, d, 3 = 9, 0 Hz), 7.70-7.95 (5H, m), 8.34 (1H, m) 13-5 7.33 (2H, m), 7.56 (2H, m), 7.7-8.0 (8H, m), 8.19 (1H, d, J = l, 4 Hz), 8.32 (1H, s), 8.56 (1H, s wide) 14-1 1.23 (3H, t, J = 7, l Hz), 2.51 (2H, m), 2.75 (2H, m), 3.55 (3H, s), 3.90 ( 3H, s), 4.10 (2H, c, J = 7, 1 Hz), 6.36 (1H, s), 7.20 (1H, d, J = 8.9 Hz) -2 -1, 30 83H, t, J = 7, l Hz), 3.56 (3H, 8), 3.82 (3H, s), 4.23 (2H, c, J = 7, 1 Hz), 6.36 (1H, s), 6.60 (1H, d, J = 16.2 Hz), 7.31 (1H, d, J = 8.6 Hz), 7.36 (1H, d, J = 16.2 Hz) - -3 3.01 (1H, m), 3.25 (1H, m), 3.57 (3H, e), 3.70, 3.73 (3H, 2s), 3.93, 3.94 (3H, 2s), 4.55 (1H, m), 6.36, 6.37 (1H, 2e), 7.26 (1H, d, J = 8.8 Hz) - -4.13 (3H, t, J = 7, l Hz), 3.03 (1H, m), 3.22 (1H, m), 3.55 (3H, e), 3.94 (3H, s), 4.14 (2H, m), 4.51 (1H, m), 6.37 (1H, s), 7.26 (1H , d, J = 8.8 Hz) - -5 1.24 (3H, t, J = 7, l Hz), 2.95 (1H, m), 3.31 (1H, m), 3.56 (3H, 8), 3.93 (3H, s), 4.16 (2H, m), 4.54 (1H, m), 6.35 (1H, s), 7.26 (1H , d, J = 8.8 Hz) - -6 0.89 (3H, t, J = 7.4 Hz), 1.61 (2H, m), 3.02 (1H, m), 3.23 (1H, m), 3.56 (3H, e), 3.94 (3H, s), 4.07 (2H, m), 4.53 (1H, m), 6.37 (1H , e), 7.25 (1H, d, J = 8.8 Hz) - -7 0.90 (3H, t, J = 7.4 Hz), 1.62 (2H, m), 2.96 (1H, m), 3.31 (1H, m), 3.56 (1H, 8), 3.94 (3H, s), 4.08 (2H, m), 4.56 (1H, m), 6.36 (1H , s), 7.25 (1H, d, J = 8.9 Hz) - -8 0.90 (3H, t, J = 7.3 Hz), 1.33 (2H, m), 1.58 (2H, m), 3.03 (1H, m), 3.22 (1H, m), 3.55 (3H, 8), 3.94 (3H, s), 4.08 (2H, m), 4.52 (1H , m), 6.37 (1H, s), 7.26 (1H, d, J = 8.8 Hz) - -9 0.91 (3H, t, J = 7.3 Hz), 1.33 (2H, m), 1.59 (2H, m ), 2.98 (1H, m), 3.32 (1H, m), 3.56 (3H, e), 3.93 (3H, e), 4.11 (2H, m), 4.56 (1H , m), 6.35 (1H, s), 7.25 (1H, d, J = 8.8 Hz) - -10 0.88 (3H, t, J = 6.7 Hz), 1.27 (4H, m), 1.60 (2H, m), 3.02 (1H, ra), 3.22 (1H, m), 3.56 (3H, s), 3.94 (3H, s), 4.09 (2H, m), 4.52 (1H , m), 6.37 (1H, s), 7.25 (1H, d, J = 8.9 Hz) - • 11 0.89 (3H, t, J = 6.7 Hz), 1.31 (4H, m), 1.61 (2H, m), 2 96 (1H, m), 3.30 (1H, m), 3.56 (3H, s), 3.93 (3H, 8), 4.10 (2H, m), 4.56 (1H, ra), 6.35 (1H, s), 7.26 (1H, d, J = 8.9 Hz) - -12 0.87 (3H, t, J = 6.4 Hz), 1.27 ( 6H, m), 1.59 (2H, m), 3.03 (1H, m), 3.22 (1H, m), 3.56 (3H, 8), 3.94 (1H, s), 4.08 (2H, m), 4.52 (1H, m), 6.37 (1H, s), 7.25 (1H, d, J = 8.8 Hz) - -13 0.88 (3H , t, J = 6.9 Hz), 1.28 (6H, m), 1, 59 (2H, m), 2.96 (1H, m), 3.32 (1H, m), 3.56 (3H, e), 3.94 (3H, e), 4.10 (2H, m), 4.56 (1H, m), 6.35 (1H, s), 7.26 (1H, d, J = 8.8 Hz) - -14 0.88 (6H, m), 1, 90 (1H, ia), 3.02 (1H, m), 3.23 (1H, m), 3.56 (3H, 8), 3.87 (2H, m), 3.94 (3H, s) ), 4.54 (1H, m), 6.37 (1H, 8), 7.25 (1H, d, J = 8, 9 Hz) - -15 0.89 (6H, m), 1.91 (1H, m), 2.96 (1H, m), 3.32 (1H, m), 3.56 (3H, 8), 3.89 (2H, m), 3.94 (3H, s) , 4.58 (1H, m), 6.35 (1H, s), 7.26 (1H, d, J = 8.9 Hz) - -16 0.89 (6H, m), 1.50 ( 1H, m), 1.60 (1H, m), 3.02 (1H, m), 3.21 (1H, m), 3.56 (3H, s), 3.94 (3H, s), 4.13 (2H, m), 4.52 (1H, m), 6.37 (1H, s), 7.25 (1H, d, J = 8.9 Hz) - -17 0.88 (6H , m), 1.49 (2H, m), 1.62 (1H, m), 2.96 (1H, m), 3.30 (1H, m), 3.56 (3H, e), 3 , 93 (3H, s), 4.14 (2H, pt), 4.56 (1H, m), 6.35 (1H, s), 7.25 (1H, d, J = 8.9 Hz) - -18 1.44, 1.46 (3H, 2e), 2.90 (1H, m), 3.31 (1H, m), 3.56 (3H, s), 3.92, 3.93 (2H, 2e), 4.42 (1H, m), 6.34, 6.37 (1H, 2s), 7.26 (1H, d, J = 9.0 Hz) - -19 2.51 ( 1H, m), 3.05 (1H, m), 3.20 (1H, m) , 3.56 (3H, s), 3.94 (3H, s), 4.59 (1H, m), 4.68 (2H, m), 6.37 (1H, s), 7.26 ( 1H, d, J = 8.9 Hz) 4-20 2.51 (1H, m), 2.99 (1H, m), 3.29 (1H, m), 3.56 (3H, 8), 3.94 (3H, s), 4.61 (1H, m), 4.70 (2H, m), 6.36 (1H, s), 7.26 (1H, d, J = 8.9 Hz) 14-21 3.0-3.3 (2H, m), 3.56 (3H, s), 3 , 93, 3.94 (3H, 2e), 4.3-4.6 (2H, m), 4.69 (1H, m), 6.35, 6.37 (1H, 2s), 7.28 (1H, d, J = 8.8 Hz) 14-22 3.06 (1H, m), 3.24 (1H, m), 3.56 (3H, s), 3.93, 3 , 94 (3H, 2e), 4.4-4.6 (2H, m), 5.86 (1H, m), 6.36, 6.37 (1H, 2s), 7.28 (1H, d, J = 8, 8 Hz) 14--23 3.04-3.21 (2H, m), 3.56 (3H, e), 4.47 , 4.65 (2H, 2m), 4.69 (1H, m), 6.37 (1H, e), 7.28 (1H, d, J = 8.7 Hz) 14--24 3.02 (1H, m), 3.24 (1H, m), 3.56 (3H, e), 3.93 (3H, s), 4.61 82H, m), 4.70 (1H, ra), 6.35 (1H, s), 7.28 (1H, d, J = 8.9 Hz) 14--25 2.98 (1H, m), 3.30 (1H, m), 3.34 ( 3H, s), 3.53 (2H, ra), 3.56 (3H, s), 3.94 (3H, s), 4.25 (2H, m), 4.62 (1H, m), 6.35 (1H, e), 7.26 (1H, d, J = 8, 9 Hz) 14--26 1.18 (3H, m), 3.05 (1H, m), 3.27 (1H, m), 3.4-3.6 (4H, m), 3.56 (3H, s), 3.93, 3.94 (3H, 2s), 4.29 (2H, m), 4.61 (1H, m), 6.35, 6.37 (1H, 2e), 7.26 (1H, d, J = 8.8 Hz) 14-27 3.04 (1H, m), 3.21 (1H, ra), 3.54 (3H, e), 3.91 (3H, s) , 4.10 (2H, m), 4.45 (2H, m), 4.61 (1H, m), 6.35 (1H, e), 6.92 (3H, m), 7.27 ( 3H, m) 14-28 2.99 (1H, m), 3.30 (1H, m), 3.55 (3H, s), 3.90 (3H, s), 4.12 (2H, m ), 4.46 (2H, m), 4.64 (1H, m), 6.34 (1H, e), 6.93 (3H, m), 7.26 (3H, m) 14-29 2 , 66 (2H, m), 3.07 (1H, m), 3.21 (1H, m), 3.56 (3H, s), 3.95 (3H, 8), 4.20 (2H, m), 4.63 (1H, m), 6.35, 6.38 (1H, 2s), 7.28 (1H, d, J = 8.9 Hz) - -30 3.08 (1H, m ), 3.22 (1H, m), 3.56 (3H, 8), 3.70 (2H, m), 3.95 (3H, s), 4.30 (1H, m), 4.51 (2H, m), 4.65 (1H, m), 6.38 (1H, s), 7.27 (1H, d, J = 8.7 Hz) - -31 3.02 (1H, m) , 3.42 (1H, m), 3.57 (3H, s), 3.72 (2H, m), 3.95 (3H, s), 4.29 (1H, m), 4.52 ( 2H, m), 4.66 (1H, ra), 6.36 (1H, s), 7.27 (1H, d, J = 8.8 Hz) - -32 1.22 (3H, t, J = 7, l Hz), 3.13 (1H, m), 3.31 (1H, m), 3.55 (3H, e), 3.95 (3H, e), 4.13 (2H, ra), 4.46 (1H, m), 6.38 (1H, e), 7, 25 (1H, d, J = 8.9 Hz) - -33 1.23 (3H, t, J = 7, l Hz), 3.08 (1H, m), 3.41 (1H, m), 3.57 (3H, e), 3.93 (3H, s), 4.12 (2H, m), 4.49 (1H, m), 6.36 (1H, s), 7.25 (1H , d, J = 8.9 Hz) - -34 1.27 (3H, m), 1.61, 1.64 (3H, 2s), 3.20 (1H, m), 3.54 (3H, s), 3.61 (1H, ra), 3.84 (3H, e), 4.18 (2H, m), 6.32, 6.37 (1H, 2e), 7.27 (1H, 2d) ) - -35 0.94 (3H, m), 1.62, 1.65 (3H, 2s), 1.67 (2H, m), 3.21 (1H, m), 3.54 (3H, s), 3.62 (1H, m), 3.84 (3H, s), 4.09 (2H, m), 6.33, 6.37 (1H, 2s), 7.27 (1H, 2d) , J = 8.8 Hz, 8.8 Hz) - -36 0.94 (3H, m), 1.41 (2H, m), 1.61, 1.65 (3H, 2s), 1.63 (2H, m), 3.21 (1H, m), 3.54 (3H, e), 3.60 (1H, m), 3.84 (3H, e), 4.12 (2H, m) , 6.32, 6.37 (1H, 2e), 7.27 (1H, 2d, J = 8.8 Hz, 8.9 Hz) - -37 0.90 (3H, m), 1.33 ( 4H, m), 1.61, 1.64 (3H, 2s), 1.65 (2H, m), 3.20 (1H, m), 3.54 (3H, s), 3.59 (1H , m), 3.84 (3H, s), 4.12 (2H, m), 6.32, 6.37 (1H, 2s), 7.27 (1H, 2d, J = 8, 9 Hz, 8.7 Hz) - -38 0.89 (3 H, m), 1.30 (4H, ra), 1.61, 1.64 (3H, 2e), 1.65 (2H, m), 3.20 (1H, m), 3.54 (3H , s), 3.59 (1H, m), 3.84 (3H, s), 4.11 (2H, m), 6.32, 6.36 (1H, 2e), 7.27 (1H, 2d, J = 8.8 Hz, 8.8 Hz) - -39 1.26 (6H, m), 1.59, 1.62 (3H, 2s), 3.20 (1H, m), 3, 54 (3H, s), 3.63 (1H, m), 3.85 (3H, s), 4.98 (1H, m), 6.32, 6.37 (1H, 2s), 7.27 (1H, 2d, J = 8.8 Hz, 8.8 Hz) - -40 9.94 (6H, ra), 1.62, 1.65 (3H, 2s), 1.96 (1H, m) , 3.21 (1H, m), 3.54 (3H, s), 3.62 (1H, m), 3.84 (3H, s), 3.92 (2H, m), 6.32, 6.37 (1H, 2e), 7.27 (1H, 2d, J = 8.8 Hz, 8.8 Hz) - -41 1.63, 1.66 (3H, 2e), 3.22 (1H , m), 3.53 (3H, e), 3.63 (1H, m), 3.79 (3H, 8), 5.16 (2H, m), 6.29, 6.36 (1H, 2s), 7.25 (1H, 2d, J = 8, 8 Hz, 8.8 Hz), 7.35 (5H, m) - -42 1.64, 1.67 (3H, 2s), 3, 23 (1H, m), 3.52, 3.55 (3H, 2s), 3.66 (1H, m), 3.84 (3H, s), 4.71 (1H, m), 5.00 (1H, m), 6.33, 6.37 (1H, 2s), 7.18 (1H, m), 7.27 (1H, 2d, J = 8.8 Hz, 8.8 Hz) - -43 1.63, 1.66 (3H, 2e), 3.21 (1H, m), 3.54 (3H , s), 3.62 (1H, m), 3.84 (3H, e), 4.63 (2H, m), 5.31 (2H, m), 5.89 (1H, m), 6 , 33, 6.37 (1H, 2s), 7.27 (1H, 2d, J = 8.9 Hz, 8.7 Hz) - -44 1.63 (3H, m), 2.52 (1H, m), 3.18 (1H, m), 3.56 (3H, s), 3.60 (1H, m), 3.84 (3H, e), 4.74 (2H, m), 6, 34, 6.37 (1H, 2e), 7.26, 7.27 (1H, 2d, J = 8.7 Hz, 8.8 HZ) - -45 1, 65, 1.68 (3H, 2s), 3.19 (1H, m), 3.51 (1H, m), 3.55 (3H, e), 3.84 (3H, 8), 4, 49 (1H, m), 5.86 (1H, m), 6.34, 6.37 (1H, 2s), 7.28 (1H, 2d, J = 8.8 Hz, 8.8 Hz) - -46 1.67, 1.68 (3H, 2s), 3.18 (1H, m), 3.53, 3.55 (3H, 2s), 3.66 (1H, m), 3.82, 3.83 (3H, 2s), 5.73 (1H, m), 6.35, 6.37 (1H, 2s), 7.31 (1H, 2d, J = 8.9 Hz, 8.8 Hz ) 4- • 47 1.63, 1.65 (3H, 2s), 3.20 (1H, m), 3.36, 3.37 (3H, 28), 3.55 (3H, s), 3 , 63 (3H, m), 3.84 (3H, s), 4.29 (2H, m), 6.33, 6.36 (1H, 2s), 7.27 (1H, 2d, J = 8 , 8 HZ, 8.8 Hz) 4-48.42, 1.64 (3H, 2s), 2.16 (3H, t, J = 2.4 Hz), 2.73 (2H, m) , 3.20 (1H, ra), 3.55 (3H, 8), 3.59 (1H, m), 3.84 (3H, s), 4.30 (2H, m), 6.33, 6.36 (1H, 2s), 7.27 (1H, 2d, J = 8.8 Hz, 8.8 Hz) 14- -49 1.63, 1.65 (3H, 2s), 1.8- 2.1 (4H, pt), 3.20 (1H, m), 3.54 (3H, e), 3.61 (1H, m), 3.81 (2H, m), 3.84 (3H , e), 4.13 (3H, m), 6.33, 6.36 (1H, e), 7.27 (1H, 2d, J = 8.7 Hz, 8.9 Hz) 14-50 3.05 (2H, m), 3.29 (1H, m), 3.52, 3.57 (3H, 2s), 3.59 (1H, m), 3.68 (3H, s), 3 , 76 (3H, s), 3.79, 3.80 (3H, 2s), 6.32, 6.35 (1H, 2s), 7.29 (1H, 2d, J = 8.9 Hz, 8.8 Hz) 14- -51 1.31, 1.35 (3H, 2t, 3 = 1.2 Hz, 7.1 Hz), 3.50 (1H, m), 3.55, 3.57 (3H, 2s), 3.68 (1H, m ), 3.92, 3.94 (3H, 2e), 4.31 (2H, m), 6.35, 6.38 (1H, e), 7.34 (1H, 2d, J = 8.9 Hz, 8.9 Hz) 14-52.26 (3H, t, J = 7, l Hz), 2.48 (3H, e), 3.07 (1H, m), 3.38 (1H , m), 4.21 (2H, c, J = 7, l Hz), 4.51 (1H, m), 7.07 (1H, t, J = 58.0 Hz), 7.23 (2H , m) 14- -53 1.24 (3H, t, J = 7, 1 Hz), 1.90 (4H, m), 3.15 (1H, m), 3.43 (1H, m), 3.65 (4H, m), 3.92 (3H, e), 4.18 (2H, m), 4.48 (1H, m), 7.26 (1H, d, J = 10.5 Hz ) 14- -54 1.16 (3H, t, J = 7.2 Hz), 2.36 (3H, s), 3.04 (1H, m), 3.26 (1H, m), 3.48. (3H, e), 4.00-4.25 (3H, m), 6.30 (1H, s), 7.20 (1H, d, J = 8.8 Hz) 14-55 1.18 ( 3H, t, J = 7.2 Hz), 2.37 (3H, s), 3.03 (1H, m), 3.31 (1H, m), 3.50 (3H, s), 4, 00-4.25 (3H, m), 6.28 (1H, s), 7.20 (1H, d, J = 8.7 Hz) -56 1.21 (3H, t, J = 7.2 Hz), 3.10-3.45 (2H, m), 3.90 (3H, s), 4.07 (3H, broad d, J = 0.9 Hz), 4.16 (2H, c, 3 = 1, 2 Hz), 4.54 (1H, broad t, J = 7.3 Hz), 7.20 (1H, d, J = 8.6 Hz) -57 3.45 (3H, d, J = 1, Hz), 6.21 (1H, s), 7.30 (1H, d, J = 8.4 Hz), 7.46 (2H, t, J = 7.5 Hz), 7.5-7.8 (5H, m) -58.31 (3H, d, J = 0, 9 Hz), 6.29 (1H, e), 6.32 (1H, d, J = 12, l Hz), 6.80 (1H, d, J = 12, l Hz), 7.15 (lH, d, J = 8.5 Hz), 7.28 (2H, m), 7.35 (1H, dd, J = 8.5 Hz), 7.42 (2H, m), 7.6-7.8 (4H, m) -59.38 (3H, e), 6.34 (1H, s), 6.72 (1H, d, J = 16.0 Hz), 7.02 (1H, d, J = 8.4 Hz), 7.18 (1H, d, J = 16.0 Hz), 7.30 (1H, dd, J = 10.7, 2.3 Hz), 7.39 (2H, m), 7.48 (1H, dd, J = 8.7, 1.2 Hz), 7.73 (5H, m) -60 1.25 (1.5H, t, J = 7, 1 Hz), 1.26 (1.5H, t, J = 7, 1 Hz), 2.92 (lHm), 3.26 (1H, m), 3.57 (3H, m), 4.22 (4H, m), 4.36 (1H, m), 6.37 (0.5H, s), 6.38 (0.5H, s) ), 7.2-7.3 (2H, m) - 61 1.21 (3H, m), 2.49 (3H, e), 3.33 (2H, m), 3.90 (3H, s), 4.18 (2H, m), 4.52 (1H, t, 3 = 1.2 Hz), 7.05 (1H, t, J = 58.0 Hz), 7.25 (1H, d, J = 8.9 Hz) --62.46 (3H, t, J = 7.0), 3.58 (3H, e), 4.12 (2H, c, J = 7.0 Hz ), 6.37 (1H, e), 7.26 (1H, d, J = 8.7 Hz) --63.22 (3H, t, J = 7.2 Hz), 1.47 (3H , t, 3 = 1, 0), 3.00 (1H, dd, J = 14.2, 5.2 Hz j, 3.23 (1H, dd, J = 14.2, 8.4 Hz), 3.55 (3H, c, J = 0.8 Hz), 4.12 (2H, c, 3 = 1.0 Hz), 4.12 (2H, m), 4.57 (1H, dd, J = 8.4, 5.2 Hz), 6.37 (1H, e), 7.26 (1H, d, J = 8.7 Hz) - 64 1.23 (3H, t, J = 7, l Hz), 1.46 (3H, t, 3 = 1.0 Hz), 2.94 (1H, dd, J = 1 4.4, 6.4 Hz), 3.32 (1H, dd, J = 14.4, 7.0 Hz), 3.55 (3H, c, J = 0.8 Hz), 4.10 ( 2H, c, J = 7.0 Hz), 4.17 (2H, c, 3 = 1, 1 Hz), 4.61 (1H, dd, J = 7.0, 6.4 Hz), 6, 34 (1H, s), 7.25 (1H, d, J = 8.9 Hz) 14-65 0.89 (3H, t, J = 7.3 Hz), 1.46 (3H, t, 3 = 1.0 Hz), 1.62 (2H, te, J = 7.3, 6.9 Hz), 3.03 (1H, dd, J = 14.2, .4 Hz), 3.21 (1H, dd, J = 14.2, 8.3 Hz), 3.55 (3H, C, J = 1.0 Hz), 4.04 (2H, c, J = 7.0 Hz), 4.10 (2H, m), 4.59 (1H, dd, J = 8.3, 5 , 4 Hz), 6.37 (1H, e), 7.25 (1H, d, J = 8.8 Hz) 14-66 0.90 (3H, t, J = 7.3 Hz), 1, 46 (3H, t, 3 = 1.0 Hz), 1.63 (2H, te, J = 7.3, 6.9 Hz), 2.94 (1H, dd, J = 14.4, 6.8 Hz), 3.32 (1H, dd, J = 14.4, 6.9 Hz), 3.55 (3H, c, J = 1.0 Hz), 4.07 (2H, c, J = 7.0 Hz), 4.10 (2H, m), 4.64 (1H, dd, J = 6.9, 6.8 Hz), 6.35 (1H, e), 7.25 ( 1H d, J = 8.9 Hz) 14-67 1.38 (6H, t, J = 6.2 Hz), 3.57 (3H, c, J = 1, 2 Hz), 4.58 (1H , c, J = 6.2 Hz), 6.37 (1H, e), 7.27 (1H, d, J = 8.7 Hz) 14-68 1.22 (3H, t, J = 7, l Hz), 1.34, 1.39 (6H, t, J = 6.2 Hz), 3.03 (1H, dd, J = 14.2, 5.3 Hz), 3.26 (1H, dd, J = 14.2, 8.3 Hz), 3.55 (3H, e), 4.14 (3H, c, 3 = 1.1) Hz), 4.58 (1H, dd, J = 8.3, 5.3 Hz), 4.68 (1H, c, J = 6.2 Hz), 6.36 (1H, e), 7, 25 (1H, d, J = 8.9 Hz) 14-69 1.22 (3H, t, J = 7, l Hz), 1.35, 1.37 (6H, t, J = 6.2 Hz), 2.94 (1H, dd, J = 14 , 4, 6.5 Hz), 3.35 (1H, dd, J = 14.4, 7.1 Hz), 3.56 (3H, e), 4.16 (3H, c, J = 7, 1 Hz), 4.64 (1H, c, J = 6.2 Hz), 4.66 (1H, dd, J = 7, l, 6.5 Hz), 6.34 (1H, s), 7.25 (1H, d, J = 8.9 Hz) 14-70 1.25 (3H, t, J = 7, l Hz), 2.39 (3H, e), 2.89 (1H, dd, J = 14.8, 7.8 Hz), 3, 23 (1H, dd, J = 14.8, 6.1 Hz), 3.56 (3H, c, J = 1.0 Hz), 4.17 (2H, c, 3 = 1.1 Hz), 4.39 (1H, dd, J = 7.8, 6.1 Hz ), 6.37, 6.38 (1H, s), 7.00 (1H, d, J = 8.0 Hz), 7.22 (1H, d, J = 8.0 Hz), 7.27 (1H, s) 14-71 0.89 (3H, m ), 1.63 (2H, m), 3.00 (1H, m), 3.30 (1H, m), 3.54, 3.55 (3H, s), 3.93 (3H, 8) , 4.09 (1H, m), 6.36, 6.38 (1H, s), 7.23 (1H, d, J = 8.2 Hz), 8.07 (1H, dd, J = 8 , 2, 1.9 Hz), 8.16 (1H, d, J = 1, 9 HZ) 14-72 0.86, 0.88 (3H, t, J = 6.8 Hz), 1.57 , 1.62 (2H, m), 2.43 (3H, s), 2.96 (1H, dd, J = 14.2, 6.0 Hz), 3.39 (1H, dd, J = 14.2, 7.2 Hz), 3.93 (3H, s), 4.05 (2H, m), 4.54 (1H, dd, J = 7, 2, 6 , 9 Hz), 7.28, 7.29 (1H, d, J = 8.8 Hz), 8.02, 8.04 (1H, e) 14--73 3.14 (2H, m), 4.54 (3H, 2s), 3.94 (3H, 2e), 4.63 (1H, m), 6.38 (1H, 2s), 7.25 (1H, d, J = 8.9 Hz), 9.5 (1H, broad) 14-74 4.06 (3H, e), 7.47 (1H, d, J = 8.4 Hz), 8.10 (1H, m), 8.80 (1H, m) 14--75 3.87 (3H, e), 6.61 (1H, d, J = 9.4 Hz), 8.12 (1H, m), 8.88 (1H, m) 15--1 3.53 (3H, s), 3.7 (2H, wide), 6.4 (1H, wide) , 6.29 (1H, s), 6.68 (1H, d, J = 9, 1 Hz) 15-2-2 0.7-0.9 (4H, m), 1.23 (1H, m) , 3.51 (3H, s), 3.87 (3H, s), 6.24 (1H, s), 6.47 (1H, s), 6.83 (1H, d, J = 9.0 Hz), 8.02 (1H, e) 15--3 3.02 (3H, e), 3.92 (3H, s), 5.99 (1H, s), 6.74 (1H, s) , 6.79 (1H, d, J = 9.0 Hz), 7.38 (2H, 2d), 7.53 (1H, 2d), 7.72 (2H, d, 3 = 1.2 Hz) , 8.85 (1H, 8) 15--4 3.31 (3H, 8), 4.05 (3H, s), 6.20 (1H, s), 6.86 (2H, m), 6.89 (1H, d, 3 = 9, 1 Hz), 7.03 (1H, ra), 8.12 (1H, m), 8.23 (1H, m) 15--5 2.91 (3H, s) ), 3.91 (3H, 8), 5.99 (1H, s), 6.76 (1H, d, J = 9.0 Hz), 6.81 (1H, s), 7.59 (2H , m), 7.82 (4H, m), 8.32 (1H, 8), 8.98 (1H, s) 15-6.11 (3H, t, J = 7, 1 Hz), 3.55 (3H, e), 3.95 (3H, e), 4.07 (2H, c, J = 7, l Hz), 6.28 (1H, e wide), 6.31 (1H, s), 6.43, (1H, s an cho), 6.87 (1H, d, J = 9, 1 Hz) 15-7.36 (3H, s), 3.93 (3H, s), 6.29 (1H, e), 6 , 52 (1H, broad s), 6.90 (1H, d, J = 9.0 Hz), 7.10 (3H, m), 7.21 (1H, m), 7.34 (2H, m ) 15- -8 3.28 (3H, 8), 3.90 (3H, s), 6.11 (1H, s), 6.66 (1H, 8), 6.84 (3H, m), 6.93 (1H, d, J = 8.9 Hz), 7.87 (1H, e), 8.07 (1H, m) 15- -9 1.33 (3H, t, J = 7, 1 hz), 3.16 (3H, e), 3.50 (3H, s), 4.05 (3H, s), 4.18 (2H, m), 6.29 (1H, s), 6, 68 (1H, e), 6.85 (1H, d, J = 9, l Hz), 9.73 (1H, s) - -10 3.54 (3H, s), 3.85 (3H, e), 5.40 (2H, m), 5.96 (1H, m), 6.32 (1H, S), 6 , 72 (1H, d, J = 9.2 Hz), 7.32 (1H, d), 8.13 (1H, e) 15- -11 0.51 (2H, m), 0.82 (2H , m), 1.27 (1H, m), 3.56 (3H, s), 3.83 (3H, s), 6.34 (1H, s), 6.67 (2H, m), 7 , 82 (1H, 8) 15- -12 1.76 (3H, s), 1.80 (3H, s), 3.54 (3H, e), 3.87 (3H, 8), 6.31 (1H, s), 6.69 (1H, d, J = 9, 1 Hz), 7.63 (1H, s) 15- -13 1.69 (3H, e), 3.39 (3H, s) ), 3.54 (3H, e), 3.83 (3H, 8), 4.13 (2H, s), 6.30 (1H, 8), 6.66 (1H, d, J = 9, 3 Hz), 9.79 (1H, e) 15- -14.0.07 (3H, e), 2.33 (2H, m), 2.52 (2H, m), 3.56 (3H, s) ), 3.36 (3H, e), 6.33 (1H, s), 6.72 (1H, d, J = 9.2 Hz), 7.06 (1H, t, J = 5, 2 Hz ), 7.92 (1H, e) 15- -15 3.30 (2H, d, J = 5.9 Hz), 3.52 (3H, s), 3.84 (3H, s), 6, 33 (1H, s), 6.72 (1H, d, 3 = 9.1 Hz), 7.07 (2H, d, J = 7.5 Hz), 7.28 (4H, ra), 7, 95 (1H, e) 15-16 1.25 (3H, t, 3 = 1.1 hz), 1.91 (3H, e), 2.98 (2H, 2d), 3.54 (3H, s) ), 3.89 (3H, s), 4.11 (2H, c, J = 7, l Hz), 6.30 (1H, s), 6.74 (1H, d, J = 9, 1 Hz ), 7.76 (1H, e) -17 1.24 (3H, m), 3.46 (1H, m), 3.50, 3.55 (3H, 2e), 3.84 (3H, s), 6.33, 6.37 (1H, 2s), 6.71 (1H, d, J = 9.2 Hz), 7.10 (3H, ra), 7.28 (3H, m), 7.91 (1H, s) 15- 18 2.32 (2H, m), 2.81 (2H, m), 3.55 (3H, s), 3.57 (2H, m), 3.94 (3H, s), 6.32 ( 1H, e), 6.74 (1H, d, J = 9, l Hz), 7.18 (4H, m), 7.75 (1H, e) 15-19 2.46 (2H, m), 2.91 (2H, m), 3.25 ( 2H, m), 3.57 (3H, e), 3.87 (3H, s), 6.36 (1H, s), 6.69 (1H, d, J = 9, l Hz), 7, 19 (4H, m), 7.64 (1H, s) 15-20 | 3.51 (3H, s), 3.90 (3H, s), 6.35 (1H, e), 6.77 (3H, m), 7.25 (1H, m), 7.83 (1H , e), 3.86 (1H, e) 15-21 3.54 (3H, s), 3.86 (3H, s), 6.31 (1H, e), 6.37 (1H, e) , 6.79 (1H, d, J = 9.3 Hz) 15-22 3.53 (3H, 8), 3.90 (3H, s), 6.41 (1H, s), 6.74 ( 1H, d, J = 9.2 Hz), 7.39 (1H, m), 7.48 (2H, m), 7.66 (2H, m), 7.80 (3H, m), 8, 34 (1H, s) TÉF? I 3.55 (3H, 8), 6.36 (1H, s), 6.61 (1H, d, J = 2, 1 Hz), 7.04 (1H, d, J = 2, l Hz), 7.97 (1H, s) 16-2 3.56 (3H, e), 3.81 (3H, s), 6.35 (1H , e), 6.94 (1H, d, J = 2.0 Hz), 7.16 (1H, d, J = 2.0 Hz) 16-3 3.54 (3H, e), 5.11 (2H, s), 6.34 (1H, 8), 6.8-6.9 (2H, m), 6.96 (1H, d, 3 = 2.0 Hz), 7.19 (1H, d, J = 2, l Hz), 7.25 (1H, m) 16-4 3 , 53 (3H, s), 6.35 (1H, s), 6.86 (1H, m), 7.00 (1H, in), 7.49 (1H, d, J = 2, 2 Hz) , 7.71 (1H, d, J = 2, 2 Hz), 8.02 (1H, m) 16-5, 3.42 (3H, e), 6.31 (1H, s), 7.49 ( 1H, d, J = 2.2 Hz), 7.61 (3H, ra), 7.93 (4H, m), 8.58 (1H, ra) 16-6 3.54 (3H, s), 3.86 (3H, s), 6.35 (1H, s), 6.82 (1H, d, J = 9.2 Hz), 6.9 (1H, broad) -7.34 (3H, s), 3.88 (3H, e), 6.26 (1H, 8), 7.29 (1H, d, J = 8.9 Hz), 7.63 (2H, m), 7.95 ( 3H, m), 8.09 (1H, 2d, J = 1.7 Hz, 8.6 Hz), 8.71 (1H, e) -1.29 (3H, s), 3.56 (3H , 8), 3.97 (3H, s), 6.37 (1H, S), 7.28 (1H, d, J = 9.0 Hz) -2.15 (6H, ra), 3.56 (3H, s), 3.73 (2H, m), 3.95 (3H, s), 6.36 (1H, 8), 7.28 (1H, d, 3 = 9.0 Hz) -3 3.51 (3H, s), 4.01 (3H, e), 4.10 (2H, m), 6.32 (1H, e), 7.24 (5H, ra), 7.30 (1H, d, J = 8.6 Hz) -4 3.14 (3H, s), 3.83 (3H, e), 6.19 (1H, 8), 7.46 (8H, m) -5 3.14 (2H, m), 3.57 (5H, m), 3 , 96 (3H, s), 6.40 (1H, e), 7.28 (1H, d, J = 9.0 Hz) The compounds of the present invention exhibit excellent herbicidal effects when used as an active ingredient of a herbicide. The herbicide can be used for a wide range of applications, for example in farmland such as rice paddies, upland agricultural areas, orchards and mulberry fields, and on uncultivated land such as forests, farm roads, playgrounds, factory areas. The application method can be suitably selected for application to soil treatment and foliar application. The compounds of the present invention are able to control noxious weeds including grasses (grasses) such as cerreig (Echinochloa crus-galli). the chicken foot (Digitaria sanguinalis), the green almorejo (Setaria viridis), the gallium (Eleusine indica L.), the mad oats (Avena fatua L.), the cañota (Sorghum halepense). the grass of the north (Agropyron relpens), the cañarejo (Brachiaria plantaginea), the garrachuelo (Panicum purpurasceri), "sprangletop" (Leptochloa chinensis) "red sprangletop" (Leptochloa Panicea); sedges (or Cyperaceae) such as the sedge of the rice fields (Cyperus i ri a L.), the purple round sedge (Cyperus rotundus L.), the lagoon junk (Scirpus ¡anoides). the lowland sedge (Cyperus serotinus), "small-flow er umbrellaplant" (Cyperus difformis), the acicular reed (Eleocharis acicularis), and the water chestnut (Eleocharis kuroguw ai): alismataceas such as the water arrow (Saggitaria pygmaea). the swallowtail (Saggitaria trifolia), and the water plantain (Alisma canaliculatum); pontederiaceas such as the camalote (Monochoria vaginalis) and monochoria sp. (Monochoria korsakow ii): escrofulariaceas such as the false chickweed (Lindernia pyxidaria) and "abunome" (Dopatrium Junceum): lithraceae such as the rotala (Rotala indica) and the red stem (Ammannia multiflora); and those of broadleaf such as the parrot (Amaranthus retroflexus), the verbasco (Abutilón theophrasti), the morning glory (Ipomoea hederacea), the ash (Chenopodium album), the spiny AIDS (Sida spinosa L.), the purslane ( Portulaca olerácea), the faint amaranth (Amaranthus viridis L.), the fallow cassia (Cassia obtusifolia), the blackberry (Solanum nigru L.), the polygon (Polygonum lapathifolium L.), the grass of the canaries (Stellaria media L .), the cadillo (Xanthium strumarium L.), the bitter cress (Cardamine flexuosa WITH.), the shoes of the virgin (Lamium amiplexicaule L.) and "threeseeded copperleaf" (Acalypha australis L.). Accordingly, it is useful for controlling weeds non-selectively or selectively in the culture of a crop plant such as corn (Zea mays L.), soybean (Glycine max Merr.), Cotton (Gossypium spp.), wheat (Triticum spp.), rice (Oryza sativa L.), oats (Avena sativa L.), sorghum (Sorchum bicolor Moench), turnip (Brassica napus L.), sunflower (Helianthus annuus L.) ), sugar beet (Beta vulgaris L.), sugar cane (Saccharum officinarum L.), Japanese grass (Zoysia Japónica stend), peanut (Arachis hypogaea L. or flax (Linum ussitatissimum, L.). For use as herbicides, the active ingredients of this invention are formulated in herbicidal compositions by mixing herbicidally active amounts with inert ingredients known in the art to facilitate either suspending, dissolving or emulsifying the active ingredient for the intended use. In the type of formulation prepared s and recognizes the fact that the formulation, culture and pattern of use can all influence the activity and usefulness of the active ingredient in a particular use. Thus for agricultural use the herbicidal compounds of the present invention can be formulated in the form of water-dispersible granules, granules for direct application to soils, water-soluble concentrates, wettable powders, dusts, solutions, emulsifiable concentrates (EC ), microemulsions, suspoemulsions, inverse emulsions or other types of formulations, depending on the target weeds, the crops and the desired application methods. These herbicidal formulations can be applied to the target area (where the objective is the removal of unwanted vegetation) in the form of dusts, granules or sprays diluted with solvent. These formulations can contain from as little as 0.1% up to as much as 97% active ingredient by weight. Dusts are mixtures of the active ingredient with finely ground materials such as clays (some examples include kaolin and montmorillonite clays), talc, granite powder or other organic or inorganic solids that act as dispersants and carriers of the active ingredient; these finely ground materials have an average particle size of less than 50 microns. A typical dustable formulation will contain 1% active ingredient and 99% carrier. Wettable powders are composed of finely ground particles that disperse rapidly in water or other carriers for sprays. Typical carriers include kaolin clays, smectite clays, silicas and other wettable, absorbent inorganic materials. The wettable powders can be prepared to contain from 1 to 90% active ingredient, depending on the desired use pattern and the absorption capacity of the carrier. Wettable powders typically contain wetting or dispersing agents to assist in dispersion in water or other carriers. Water-dispersible granules are granulated solids that freely disperse when mixed in water. This formulation typically consists of the active ingredient (from 0, 1 to 95% active ingredient), a wetting agent (1-15% by weight), a dispersing agent (from 1 to 15% by weight) and an inert carrier (from 1 to 95% by weight). The water-dispersible granules can be formed by mixing the ingredients intimately, then adding a small amount of water on a rotating disk (said mechanism is commercially available) and collecting the agglomerated granules. Alternatively, the mixture of ingredients can be mixed with an optimum amount of liquid (water or other liquid) and passed through an extruder (said mechanism is commercially available) equipped with steps that allow the formation of small extruded granules. Alternatively, the mixture of ingredients can be granulated using a high speed mixer (said mechanism is commercially available) by adding a small amount of liquid and mixing at high speeds to affect the agglomeration. Alternatively, the mixture of ingredients can be dispersed in water and dried by spraying the dispersion through a heated nozzle in a process known as spray drying (spray drying equipment is commercially available). After granulation, the moisture content of the granules is adjusted to an optimum level (generally less than 5%) and the product is calibrated to the desired mesh size. Granules are granulated solids that do not easily disperse in water, but instead maintain their physical structure when applied to the soil using a dry granule applicator. These granulated solids may be made of clay, vegetable substance such as corn pit, agglomerated silicas or other agglomerated organic or inorganic materials or compounds such as calcium sulfate. The formulation typically consists of the active ingredient (from 1 to 20%) dispersed on or absorbed in the granule. The granule can be produced by intimately mixing the active ingredient with the granules with or without a sticky agent to facilitate adhesion of the active ingredient to the surface of the granule, or by dissolving the active ingredient in a solvent, by spraying the dissolved active ingredient and the solvent over the granule and drying to remove the solvent. Granular formulations are useful when an application in furrows or fringes is desired. Emulsifiable concentrates (CE) are homogeneous liquids composed of a solvent or mixture of solvents such as xylenes, heavy aromatic naphthas, isophorone or other appropriate commercial compositions derived from petroleum distillate products, the active ingredient and an emulsifying agent or agents. For use as a herbicide, the EC is added to water (or another carrier for spraying) and applied as a spray to the target area. The composition of an EC formulation may contain from 0.1% to 95% active ingredient, from 5 to 95% solvent or solvent mixture and from 1 to 20% emulsifying agent or emulsifying agent mixture. Concentrated suspension product formulations (also known as flowable product) are liquid formulations that consist of a finely ground suspension of the active ingredient in a carrier, typically water or a non-aqueous carrier such as an oil. The suspension concentrate products typically contain the active ingredient (5 to 50% by weight), the carrier, the wetting agent, the dispersing agent, the antifreeze, the viscosity modifiers and the pH modifiers. For application, emulsion concentrate products are typically diluted with water and sprayed onto the target area. The concentrated products in solution are solutions of the active ingredient (from 1 to 70%) in solvents that have sufficient dissolution capacity to dissolve the desired amount of active ingredient. Because they are simple solutions without other inert ingredients such as wetting agents, additional additives are usually added to the spray tank mixture before spraying to facilitate proper application. Microemulsions are solutions that consist of the active ingredient (from 1 to 30%) dissolved in a surfactant or emulsifier, without any additional solvent. No additional solvents are added to this formulation. Microemulsions are particularly useful when a low odor formulation is required such as in residential turf applications. Suspoemulsions are combinations of two active ingredients. An active ingredient is formed by a concentrated product in suspension (from 1 to 50% of active ingredient) and the second active is formed by a concentrated emulsifiable product (from 0.1 to 20%). One reason for making this type of formulation is the inability to make a CE formulation of the first ingredient due to its poor solubility in organic solvents. The formulation in suspoemulsion allows the combination of the two active ingredients to be packaged in a container, thereby minimizing packaging expense and providing greater convenience to the user of the product. The herbicidal compounds of this invention can be formulated or applied with insecticides, fungicides, acaricides, nematocides, fertilizers, plant growth regulators or other agricultural chemicals. Certain additives can be added for mixing in tanks, such as fixatives for propagators, penetration coadjuvants, wetting agents, surfactants, emulsifiers, humectants and UV protectants in amounts of 0.01% to 5% to enhance biological activity, stability, wetting, dispersion on the foliage or taking of the active ingredients in the target area or to improve the ability to form suspension, dispersion, redispersion, emulsification capacity, UV stability or other physical properties or physical-chemical of the active ingredient in the spray tank, the spray system or the target area. The compositions of the present invention can be used mixed or combined with other agricultural chemicals, fertilizers, adjuvants, surfactants, emulsifiers, oils, polymers or phytotoxicity reducing agents such as protectants. In such a case, they may show even better effects or activities. As for the other agricultural chemicals, there may be mentioned, for example, herbicides, fungicides, antibiotics, plant hormones, plant growth regulators, insecticides or acaricides. It is especially possible to improve the herbicidal activities, the time interval or times of application and the range of types of weeds to which it can be applied with the herbicidal compositions having the compounds of the present invention mixed or combined with one or more ingredients assets of other herbicides. Additionally, compounds of the present invention and an active ingredient of another herbicide can be formulated separately so that they can be mixed for use at the time of application, or both can be formulated together. The present invention encompasses such herbicidal compositions. The mixing ratio of such compounds of the present invention with the active ingredient of other herbicides can not be defined in a general manner, since it varies depending on the time and the method of application, the climatic conditions, the type of soil and the type of formulation. However, an active ingredient of another herbicide can be incorporated normally in an amount of 0.01 to 100 parts by weight, on one part by weight of the compounds of the present invention. Additionally, the total dose of all active ingredients is usually from 1 to 10,000 g / ha, preferably from 5 to 500 g / ha. The present invention encompasses such herbicidal compositions. As for the active ingredients of other herbicides, the following ones can be mentioned (common name). The herbicidal compositions in which the compounds of the present invention are used in combination with other herbicides may occasionally show a synergistic effect. 1. Those that are believed to exhibit herbicidal effects by disrupting the auxin activities of plants, including those of the phenoxyacetic acid type such as 2,4-D, 2,4-DB, 2,4-DP, MCPA, MCPP, MCPB or naproanilide (including the free acids, esters or salts thereof), those of the aromatic carboxylic type such as 2,3,6-TBA, dicamba, dichlobenil, those of the pyridine type such as picloram (including the free acids and the salts thereof), triclopyr or clopyralid and others such as naptalam, benazoin, quinclorac, quinmerac or diflufenzopyr (BAS 654H). 2. Those that are believed to show herbicidal effects by inhibiting the photosynthesis of plants including those of urea type such as diuron, linuron, isoproturon, chlorotoluron, metobenzuron, tebutiuron or fluometuron, triazine type such as simazine, atrazine, cyanazine, terbutilazine , atraton, hexazinone, metribuzin, symmetry, ametryn, prometryn, dimethamethrin, or triaziflam, those of the uracil type such as bromacil, terbacillus or lenacil, those of anuid type such as propanil or cypromid, those of the carbamate type such as desmedifan or fenmedifan, those of hydroxybenzonitrile type such as bromoxynil or ioxynil, and others such as priridate, bentazon and metazole. 3. The quaternary ammonium salt type such as paraquat, dicuat or difenzocuat, which is believed to become free radicals by themselves to form active oxygen in the plant and thereby exhibit rapid herbicidal effects. 4. Those that are believed to show herbicidal effects by inhibiting the biosynthesis of chlorophyll in plants and abnormally accumulate a photosensitizing peroxide substance in the plant organism, including those of the diphenyl ether type such as nitrophen, lactofen, acifluorfen-sodium, oxyfluorfen , fomesafen, bifenox, or clometoxifen, those of cyclic imide type such as chlorftalim, flumioxazine, cinidon-ethyl, or flumiclorac-pentyl, and others such as oxadiazon, sulfentrazone, thidiazimine, azaphenidine, carfentrazone, isopropazole, flutiacet-methyl, pentoxazone, pyraflufen-ethylene and oxadiargyl. 5. Those that are believed to exhibit herbicidal effects characterized by whitening activities by inhibiting the chromogenesis of plants such as carotenoids including those of the pyridazinone type such as norflurazon, chloridazon or metflurazon, those of pyrazole type such as pyrazolate, pírazoxifen or benzofenap , and others such as fluridone, fluramone, diflufencam, methoxyphenone, clomazone, amitrol, sulcotrione, mesotrione, isoxaflutole and isoxaclortol. 6. Those showing herbicidal effects specifically for grasses including those of the aryloxyphenoxypropionic acid type (either in the form of a mixture of isomers in the form of resolved isomers) such as diclofop-methyl, pyrophop-sodium, fluazifop-butyl or fluazifop- p-butyl, haloxifop-methyl, quizalofop-p-ethyl, quizalafop-p-tefuryl, fenoxaprop-ethyl or fenoxaprop-p-ethyl, flamprop-M-methyl or flamprop-m-isopropyl or cycloophor-butyl and those of the cyclohexanedione type such as alloxidim-sodium, sethoxydim, clethodim, tepraloxydim or tralkoxidim. 7. Those that are believed to show herbicidal effects by inhibiting the amino acid biosynthesis of plants, including those of the sulfonylurea type such as chlorimuromethyl, nicosulfuron, metsulfuron-methyl, triasulfuron, prismisulfuron, tribenuron-methyl, chlorosulfuron, bensulfuron-methyl , sulfometuron-methyl, prosulfuron, halosulfuron or halosulfuron-methyl, trifensulfuron-methyl, rimsulfuron, azimsulfuron, flazasulfuron, mazosulfuron, cyclosulfamuron, flupirsulfuron, iodosulfuron, ethoxysulfuron, flucarbazone, sulfosulfuron, oxasulfuron, those of triazolopyrimidine-sulfonamide type such as flumetsulam, metosulam, cloransulam or cloransulam-methyl, those of the imidazolinone type such as imazapyr, imazetapyr, imazaquin, imazamox, imazamet, imazametabenz methyl, those of the pyrimidino salicylic acid type such as pirtiobac-sodium, pispiribac-sodium, piriminobac-methyl or piribenzoxim (LGC- 40863), and others such as glyphosate, glyphosate-ammonium, glyphosate-isopropylamine or sulfosate. 8. Those that are believed to show herbicidal effects by interfering with the normal metabolism of inorganic nitrogen assimilation such as glufosinate, glufosinate-ammonium, phosphonitrocin or bialofos. 9. Those that are believed to exhibit herbicidal effects by inhibiting the cell division of plant cells, including those of the dinitroaniline type such as trifluralin, oryzalin, nitralin, pendametalin, etafluralin, benefin and prodiamine, and those of amide type such as bensulide, napronamide, and pronamide, those of carbamate type such as profam, chlorprofam, barban, and asulam, those of organophosphorus type such as amiprophos-methyl or butamiphos and others such as DCPA and dithiopyr. 10. Those believed to exhibit herbicidal effects by inhibiting protein synthesis of plant cells, including those of the chloroacetanilide type such as alachlor, metolachlor (including combinations with protectants such as benoxacor, or resolved isomer mixtures of metolachlor including protectants such as benoxacor ), propachlor, acetochlor (including combinations with herbicide protectants such as dichlormid or MON 4660 or resolved isomeric mixtures of acetochlor containing protectants such as dichlormid or MON 4660), propisoclor or dimethenamide or those of the oxyacetamide type such as flufenacet. 11. Those in which the mode of action causing the herbicidal effects is not well known including the dithiocarbamates such as thiobencarb, EPTC, dialate, trialate, molinate, pebulate, cycloate, butylate, vernolate or prosulfocarb and miscellaneous herbicides such as MSMA, DSMA, endothelium, ethofumesate, sodium chlorate, pelargonic acid and fosamine. Some examples of formulation of the present invention are given below.

Formulation example 1. Emulsifiable concentrate Formulation example 2. Suspension concentrate Formulation Example 3. Wettable Powder Formulation Example 4. Water Dispersible Granules Test Example A standardized greenhouse herbicide activity tracking system was used to evaluate the herbicidal efficacy and safety for the culture of these test compounds. Seven species of broadleaf weeds were used, including the bledo (Amaranthus retroflexus, AMARE), the verbasco (Abutilón theophrasti, ABUTH), the fallow cassia (Cassia obtusifolia, CASOB), the morning glory (Ipomoea hederacea, IPOHE), ash (Chenopodium album, CHEAL), ambrosia (Ambrosia-artemisiifolia, AMBEL), and the cadilla (Xanthium strumarium, XANST) as test species. Likewise, four species of grass weeds were used, including the green almorejo (Setaria viridis, SETVI), the cerreíg (Echinochloa crus-galli, ECHCG), the cannone (Sorghum halepense, SORHA), and the claw nucuelo (Digitaria sanguinalis, DIGSA). In addition, three crop species were included: field corn (Zea mays L. var. Dekalb 535, CORN), soybean (Glycine max L. var. Pella 86, SOY), and upland rice (Oryza sp. var. Tebonnet, RICE).

Pre-emergency test All the plants were grown in 10 cm plastic pots which were filled with a mixture of soil with sandy loam. For the pre-emergence tests, seeds were planted one day before the application of the test compounds. For post-emergence trials the seeds were planted 8-21 days before the test to allow emergence and good foliage development before the application of the test substances. At the time of post-emergence application, plants of all species were normally in the development phase of 2-3 leaves. All test compounds were dissolved in acetone and applied to the test units in a volume of 187 I / ha. The test substances were applied at intervals of 15 g ai / ha to 1,000 g ai / ha using a tank sprayer equipped with a uniform flow flat fan spray nozzle TJ8001E. The plants were arranged on a shelf so that the upper part of the canopy (post-emergence) or the upper part of the earth surface (pre-emergence) was 40-45 cm below the nozzle. Pressurized air was used to force the test solution through the nozzle as it was mechanically advanced (via an electrically driven chain drive) over the top of all test plants / sherds. This application simulates a typical application of the herbicide in the commercial field Post-emergency test In the post-emergence test, a commercial nonionic surfactant (0.25% v / v) was also included to enhance wetting of the leaf surfaces of the target plants. Immediately after the application, the soil surfaces of the test units of the pre-emergence applications were flooded to incorporate the test substances. Subsequently, the bases of these test units were flooded. The bases of the post-emergency test units were always waterlogged. After 14 days of the application of the test substances, the phytotoxicity classifications were registered. A rating scale of 0-100 was used as previously described in Research Methods in Weed Science, 2- edition, B. Truelove, Ed., Southern Weed Science Society, Auburn University, Auburn, Alabama, 1977. In summary, "0" corresponds to no damage and "100" corresponds to the complete death of all plants in the test unit. This scale was used both to determine effectiveness against weed species and damage to crop species. The data of the herbicidal activity for some compounds of this invention, which are shown by the Compound No. of Tables 1-8, are shown in Tables 11 and 12. The data show significant differences between the compounds both for effectiveness against weeds and for selectivity for the species of culture. For the selected compounds, excellent activity was observed against a large part of the weed species with minimal damage to at least one of the crop species. The following Table XIX shows the comparative data of the pre-emergence herbicidal activity of compound 1.4 of the present invention and compound 2 referred to in Japanese Patent Toku Kai Hei 5-25144 (1993). The data clearly shows the high level of activity observed with compound 1.4.

Lh O Ul TABLE XIX Comparative herbicidal activity of compounds 1.4 and 2 O O K I Ul Tables XX and XXI show the data of the pre-emergence and post-emergence herbicidal activity respectively for some representative examples of the compounds described herein. TABLE XX Activity Pre-emergence herbicide NJ O Ln O u, C / i TABLE XXI Post-emergence herbicidal activity ro?

Claims

CLAIMS A compound represented by formula I or its salts wherein X is hydrogen, halogen, nitro, amino, NHR, N (R) 2, amide, thioamide, cyano, alkylcarbonyl, alkoxycarbonyl, alkylsulfonamide, unsubstituted or substituted alkyl, haloalkyl, alkoxy, haloalkoxy, alkoxycarbonylalkoxy, benzyloxy, aryloxy, or heteroaryloxy; And it is hydrogen, halogen, or nitro; W is hydrogen, OR, SR, NHR, N (R) 2, CH2R, CH (R) 2, C (R) 3 > halogen, nitro, or cyano, wherein multiple R groups represent any possible combination of the substituents described by R; R is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, alkoxy, cycloalkyloxy, aryloxy, heteroaryloxy, alkylsulfonyl, benzyl, alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, aryloxycarboriyl, or heteroaryloxycarbonyl, where any of these groups may be unsubstituted or substituted by any of the functional groups represented by one or more of the following: halogen, cyano, nitro, amino, carboxyl, alkyl, haloalkyl, alkylsilyl, alkylcarbonyl, haloalkylcarbonyl, alkoxy, alkoxycarbonyl, haloalkoxy, haloalkoxycarbonyl, alkylsulfonyl, haloalkylsulfonyl, aryl, heteroaryl, or cycloalkyl; Q is a heterocycle, examples of which are the following: where Rg is hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, amino, alkoxyalkyl, acetyl, alkoxycarbonylamino, alkylcarbonylamino, or alkoxycarbonyl; R2 is alkyl or haloalkyl;
R. and R2 could be combined to form a five or six membered heterocyclic ring; R3 is hydrogen, halogen, nitro, amino, alkylamino, haloalkylamino, cyano, or amide; R8 and Rg are independently oxygen, sulfur, or a minimum group; Q6, Q7, and Q10 may optionally be unsaturated containing one or two double bonds in the six membered ring;
Z is amino, hydroxyl, thiol, formyl, carboxyl, cyano, alkylcarbonyl, arylcarbonyl, azido, or one of the following: wherein R4 is alkyl, alkenyl, alkynyl, amino, cycloalkyl, heterocycloalkyl, alkylsulfonyl, arylsulfonyl, benzyl, aryl, heteroaryl, alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, cycloalkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, alkylthiocarbonyl, cycloalkyloxycarbonyl, aryloxycarbonyl, arylthiocarbonyl, arylthiocarbonyl, heteroaryloxycarbonyl , aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, heteroarylaminocarbonyl, alkoxycarbonylcarbonyl or arylcarbonylcarbonyl, wherein any of these groups may be unsubstituted or substituted by any one of the functional groups represented by one or more of the following: halogen, cyano, nitro, amino, dialkylamino , hydroxyl, carboxyl, alkyl, alkenyl, alkynyl, cycloalkyl, alkylcarbonyl, alkylcarbonyloxy, alkoxy, alkoxycarbonyl, alkylthio, alkylthiocarbonyl, alkoxythiocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, alkylsulfonyl, alkenyloxy arbonyl, alkynyloxycarbonyl, aryl, arylcarbonyl, aryloxy, aryloxycarbonyl, arylthio, heteroaryl, heteroaryloxycarbonyl or methylenedioxy, wherein the alkyl radical or the aryl radical may be substituted with halogen, cyano, nitro, alkyl, alkoxy, haloalkyl, haloalkoxy, alkoxycarbonyl, cycloalkyl, aryl, or heterocycloalkyl; and R5 is hydrogen or any one of the groups represented by R4; or R4 and R5 could be combined to form a 4- to 8-membered heterocyclic ring; where R6 represents unsubstituted or substituted alkyl, haloalkyl, dialkylamino, and aryl and heteroaryl; and R7 represents hydrogen, halogen or any of the groups represented by R6; -OR4, -SR4, -CH2R? or, -CH (R10) 2, -C (R10) 3, or ~ GH = CHR-? or where R10 is carboxyl, alkyl, alkenyl, alkynyl, amino, cycloalkyl, heterocycloalkyl, alkylsulfonyl, arylsulfonyl, benzyl, aryl, heteroaryl , alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, cycloalkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, alkylthiocarbonyl, cycloalkyloxycarbonyl, aryloxycarbonyl, arylthiocarbonyl, arylthiocarbonyl, heteroaryloxycarbonyl, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, heteroarylaminocarbonyl, alkoxycarbonylcarbonyl or arylcarbonylcarbonyl, wherein any of these groups may be unsubstituted or substituted with any of functional groups represented by one or more of the following: halogen, cyano, nitro, amino, dialkylamino, hydroxyl, carboxyl, alkyl, alkenyl, alkynyl, cycloalkyl, alkylcarbonyl, alkylcarbonyloxy, alkoxy, alkoxycarbonyl, alkylthio, alkylthiocarbonyl, alkoxythiocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, alkylsulfonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, aryl, arylcarbonyl, aryloxy, aryloxycarbonyl, arylthio, heteroaryl, heteroaryloxycarbonyl or methylenedioxy, wherein the alkyl radical or the aryl radical may be Halogen, cyano, nitro, alkyl, alkoxy, haloalkyl, haloalkoxy, alkoxycarbonyl, cycloalkyl, aryl, or heterocycloalkyl; provided that (1) Z is not alkyl, alkoxy, haloalkyl, haloalkoxy, alkylthio, haloalkylthio, alkenyl, haloalkenyl, amino, monoalkylamino, dialkylamino, alkoxyalkoxy or cyano, when Q is Q1 and R2 is haloalkyl, (2) Z is not amino when Q is Q3, and (3) Z is not hydroxyl, alkoxy, alkenyloxy, alkynyloxy, haloalkoxy, haloalkenyloxy, or -NR4R5, where R4 is alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl, haloalkenyl, alkylsulfonyl, alkylcarbonyl, alkoxycarbonyl, or cycloalkylalkyl, and R5 is alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl, haloalkenyl, alkylcarbonyl, alkoxycarbonyl, or cycloalkylalkyl, when Q is Q14 or Q15. 2. The compound according to claim 1, wherein Z is represented by the following: wherein R4 and R5 are defined as in claim 1; or -CH2R10, wherein R10 is defined as in claim 1. 3. The compound according to claim 1 or 2, wherein X is halogen or cyano; And it's halogen; W is OR; R is alkyl, alkenyl, or alkynyl, wherein any of these groups may be unsubstituted or substituted with any of the functional groups represented by one or more of the following: halogen, cyano, nitro, amino, or carboxyl.
4. The compound according to claim 1, wherein Q is
Q1 Q6 where Ri is alkyl, amino, or haloalkyl; R2 is haloalkyl; R3 is hydrogen; R8 and R9 are independently oxygen, sulfur, or an imino group. 5. The compound according to claim 1, wherein X is halogen; And it is fluorine; W is OR; R is alkyl, alkenyl, or alkynyl, wherein any of these groups may be unsubstituted or substituted by halogen or cyano; What is it
Q1 Q6 where Ri is alkyl, amino, or haloalkyl; R2 is haloalkyl; R3 is hydrogen; R8 and R9 are independently oxygen, sulfur, or an imino group; Z is represented by the following: where R is alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, cycloalkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, alkylthiocarbonyl, cycloalkyloxycarbonyl, aryloxycarbonyl, arylthiocarbonyl, arylthiocarbonyl, heteroaryloxycarbonyl, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, heteroarylaminocarbonyl, alcoxicarbonilcarbonilo or arilcarbonilcarbonilo where any of these groups may not be substituted or substituted by any of the functional groups represented by one or more of the following: halogen, cyano, nitro, amino, dialkylamino, hydroxyl, carboxyl, alkyl, alkenyl, alkynyl, cycloalkyl, alkylcarbonyl, alkylcarbonyloxy, alkoxy, alkoxycarbonyl, alkylthio , alkylthiocarbonyl, alkoxythiocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, alkylsulfonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, aryl, arylcarbonyl, aryloxy, aryloxycarbonyl, arylthio, heteroaryl, heteroaryloxycarbonyl or methylene oxy, wherein the alkyl radical or the aryl radical may be substituted with halogen, cyano, nitro, alkyl, alkoxy, haloalkyl, haloalkoxy, alkoxycarbonyl, cycloalkyl, aryl, or heterocycloalkyl; and R5 is hydrogen; or -CH2R? or, wherein R10 is carboxyl, alkyl, alkenyl, or alkynyl, wherein any of these groups may be unsubstituted or substituted with any of the functional groups represented by one or more of the following: halogen, cyano, nitro amino, dialkylamino, hydroxyl, carboxyl, alkyl, alkenyl, alkynyl, cycloalkyl, alkylcarbonyl, alkylcarbonyloxy, alkoxy, alkoxycarbonyl, alkylthio, alkylthiocarbonyl, alkoxythiocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, alkylsulfonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, aryl, arylcarbonyl, aryloxy, aryloxycarbonyl, arylthio , heteroaryl, heteroaryloxycarbonyl or methylenedioxy, wherein the alkyl radical or the aryl radical may be substituted with halogen, cyano, nitro, alkyl, alkoxy, haloalkyl, haloalkoxy, alkoxycarbonyl, cycloalkyl, aryl, or heterocycloalkyl. 6. A compound selected from the group consisting of 3- (2-amino-4-chloro-6-fluoro-3-methoxy-phenyl) -1-methyl-6-trifluoromethyl-2,4 (1H, 3H) -pyrimidinedione and 3- (2-amino-4-chloro-6-fluoro-3-methoxyphenyl) -1-amino-6-trifluoro methyl-2,4 (1 H, 3H) -pyrimidinedione.
7. A herbicidal composition, wherein it contains at least one compound according to claim 1 and an agricultural adjuvant.
8. A method for controlling unwanted vegetation comprising applying to a site to protect a herbicide-effective amount of a compound of claim 1.
9. The method of claim 8, wherein the site to be protected is a cereal crop field. The method of claim 9, wherein the compound of claim 1 is applied to a soil as a preemergence herbicide. The method of claim 9, wherein the compound of claim 1 is applied to the foliage of the plants. 12. A method for defolling potato and cotton using a compound of claim 1. 13. A process for preparing a compound represented by formula 1-1 or its salts: 1-1 wherein X is hydrogen, halogen, nitro, amino, NHR, N (R) 2, amide, thioamide, cyano, alkylcarbonyl, alkoxycarbonyl, alkylsulfonamide, unsubstituted or substituted alkyl, haloalkyl, alkoxy, haloalkoxy, alkoxycarbonylalkoxy, benzyloxy, aryloxy, or heteroaryloxy; And it is hydrogen, halogen, or nitro; W is hydrogen, OR, SR, NHR, N (R) 2, CH2R, CH (R) 2, C (R) 3, halogen, nitro, or cyano, where multiple R groups represent any possible combination of the substituents described by R; R is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, alkoxy, cycloalkyloxy, aryloxy, heteroaryloxy, alkylsulfonyl, benzyl, alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, or heteroaryloxycarbonyl, where any of these groups may be unsubstituted or substituted by any of the functional groups represented by one or more of the following: halogen, cyano, nitro, amino, carboxyl, alkyl, haloalkyl, alkylsilyl, alkylcarbonyl, haloalkylcarbonyl, alkoxy, alkoxycarbonyl, haloalkoxy, haloalkoxycarbonyl, alkylsulfonyl, haloalkylsulfonyl, aryl, heteroaryl, or cycloalkyl; Q is a heterocycle, examples of which are the following: where Ri is hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, amino, alkoxyalkyl, acetyl, alkoxycarbonylamino, alkylcarbonylamino, or alkoxycarbonyl; R2 is alkyl or haloalkyl; Ri and R2 could be combined to form a five or six membered heterocyclic ring; R3 is hydrogen, halogen, nitro, amino, alkylamino, haloalkylamino, cyano, or amide; R8 and R9 are independently oxygen, sulfur, or an imino group; Q6, Q7, and Q10 may optionally be unsaturated containing one or two double bonds in the six membered ring; Z 'is one of the following: where R 4 is alkyl, alkenyl, alkynyl, amino, cycloalkyl, heterocycloalkyl, alkylsulfonyl, arylsulfonyl, benzyl, aryl, heteroaryl, alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, cycloalkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, alkylthiocarbonyl, cycloalkyloxycarbonyl, aryloxcarbonyl, arylthiocarbonyl, arylthiocarbonyl , heteroaryloxycarbonyl, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, heteroarylaminocarbonyl, alkoxycarbonylcarbonyl or arylcarbonylcarbonyl, wherein any of these groups may be unsubstituted or substituted by any of the functional groups represented by one or more of the following: halogen, cyano, nitro, amino, dialkylamino, hydroxyl, carboxyl, alkyl, alkenyl, alkynyl, cycloalkyl, alkylcarbonyl, alkylcarbonyloxy, alkoxy, alkoxycarbonyl, alkylthio, alkylthiocarbonyl, alkoxythiocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, alkylsulfonyl, alkenyloxycarbo nyl, alkynyloxycarbonyl, aryl, arylcarbonyl, aryloxy, aryloxycarbonyl, arylthio, heteroaryl, heteroaryloxycarbonyl or methylenedioxy, wherein the alkyl radical or the aryl radical can be substituted with halogen, cyano, nitro, alkyl, alkoxy, haloalkyl, haloalkoxy, alkoxycarbonyl, cycloalkyl, aryl, or heterocycloalkyl; and R5 is hydrogen or any one of the groups represented by R4; or R4 and R5 could be combined to form a 4- to 8-membered heterocyclic ring; where R6 represents unsubstituted or substituted alkyl, haloalkyl, dialkylamino, and aryl and heteroaryl; and R7 represents hydrogen, halogen or any of the groups represented by R6; -CH (R1 or) 2. -C (R10) 3, or -CH = CHR? Or where R10 is carboxyl, alkyl, alkenyl, alkynyl, amino, cycloalkyl, heterocycloalkyl, alkylsulfonyl, arylsulfonyl, benzyl, aryl, heteroaryl, alkylcarbonyl , alkenylcarbonyl, alkynylcarbonyl, cycloalkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, alkylthiocarbonyl, cycloalkyloxycarbonyl, aryloxycarbonyl, arylthiocarbonyl, arylthiocarbonyl, heteroaryloxycarbonyl, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonium, heteroarylaminocarbonyl, alkoxycarbonylcarbonyl or arylcarbonylcarbonyl, wherein any of these groups may be unsubstituted or substituted by any of the functional groups represented by one or more of the following: halogen, cyano, nitro, amino, dialkylamino, hydroxyl, carboxyl, alkyl, alkenyl, alkynyl, cycloalkyl, alkylcarbonyl, alkylcarbonyloxy, alkoxy, alkoxycarbonyl, alkylthio, alkylthiocarbonyl, alkoxythiocarbonyl, alkylaminocarbonyl, arifaminocarbonyl, alkylsulfonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, aryl, arylcarbonyl, aryloxy, aryloxycarbonyl, arylthio, heteroaryl, heteroaryloxycarbonyl or methylenedioxy, wherein the alkyl radical or the aryl radical may be substituted with halogen, cyano, nitro, alkyl, alkoxy, haloalkyl, haloalkoxy, alkoxycarbonyl, cycloalkyl, aryl, or heterocycloalkyl; provided that (1) Z 'is not alkyl, haloalkyl, alkenyl, haloalkenyl, monoalkylamino, or dialkylamino, when Q is Q1 and R2 is haloalkyl, and (2) Z' is not -NR4R5, where R4 is alkyl, alkenyl, alkynyl , cycloalkyl, haloalkyl, haloalkenyl, alkylsulfonyl, alkylcarbonyl, alkoxycarbonyl, or cycloalkylalkyl, and R5 is alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl, haloalkenyl, alkylcarbonyl, alkoxycarbonyl, or cycloalkylalkyl, when Q is Q14 or Q15, which comprises reacting a compound represented by formula II: with a compound selected from the group consisting of an alkyl halide, alkyl acid halide, aryl acid halide, alkyl acid anhydride, aryl acid anhydride, alkyl haloformate, alkyl isocyanate, aryl isocyanate, alkyl dihalide, aldehyde aliphatic, aliphatic ketone, aromatic aldehyde, and aromatic ketone. 14. A compound represented by the formula III: wherein X is hydrogen, halogen, nitro, amino, NHR, N (R) 2, amide, thioamide, cyano, alkylcarbonyl, alkoxycarbonyl, alkylsulfonamide, unsubstituted or substituted alkyl, haloalkyl, alkoxy, haloalkoxy, alkoxycarbonylalkoxy, benzyloxy, aryloxy, or heteroaryloxy; And it is hydrogen, halogen, or nitro; W is hydrogen, OR, SR, NHR, N (R) 2, CH2R, CH (R) 2, C (R) 3, halogen, nitro, or cyano, where multiple R groups represent any possible combination of the substituents described by R; R is hydrogen, alkyl, alkenyl, alkynyl, cycloalkio, aryl, heteroaryl, alkoxy, cycloalkyloxy, aryloxy, heteroaryloxy, alkylsulfonyl, benzyl, alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, or heteroaryloxycarbonyl, where any of these groups may be unsubstituted or substituted by any of the functional groups represented by one or more of the following: halogen, cyano, nitro, amino, carboxyl, alkyl, haloalkyl, alkylsilyl, alkylcarbonyl, haloalkylcarbonyl, alkoxy, alkoxycarbonyl, haloalkoxy, haloalkoxycarbonyl, alkylsulfonyl, haloalkylsulfonyl, aryl, heteroaryl, or cycloalkyl; Q is a heterocycle, examples of which are the following: Q11 Q12 where R ^ is hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, amino, alkoxyalkyl, acetyl, alkoxycarbonylamino, alkylcarbonylamino, or alkoxycarbonyl; R2 is alkyl or haloalkyl; Ri and R2 could be combined to form a five or six membered heterocyclic ring; R3 is hydrogen, halogen, nitro, amino, alkylamino, haloalkyl, cyano, or amide; R8 and R9 are independently oxygen, sulfur, or an imino group; Q6, Q7, and Q10 may optionally be unsaturated containing one or two double bonds in the six membered ring; M is nitro. 15. A compound represented by the following formulas IV or V: IV V where X 'and Y' are halogens; and R is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, alkoxy, cycloalkyloxy, aryloxy, heteroaryloxy, alkylsulfonyl, benzyl, alk? lcarbonilo, alkenylcarbonyl, alkynylcarbonyl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, or heteroaryloxycarbonyl, where any of these groups may be unsubstituted or substituted with any of the functional groups represented by one or more of the following: halogen, cyano, nitro, amino, carboxyl, alkyl, haloalkyl, alkylsilyl, alkylcarbonyl, haloalkylcarbonyl, alkoxy, alkoxycarbonyl, haloalkoxy , haloalkoxycarbonyl, alkylsulfonyl, haloalkylsulfonyl, aryl, heteroaryl, or cycloalkyl.