Patent GB-1325527-A (GB)
Title: Aminophenylamidine derivatives their production and their pharmaceutical use
IPC: C07C239/00
Filed: 1971-06-11
Abstract: 1325527 Aminophenylamidine derivatives BAYER AG 11 June 1971 [13 June 1970] 27493/71 Heading C2C Aminophenylamidine derivatives of the Formula I wherein R is a straight or branched-chain alkyl, alkenyl or alkoxy group; R<SP>2</SP> is a -COR<SP>6</SP> group or an -SO 2 R<SP>7</SP> group [in which R<SP>6</SP> is a hydrogen atom; a straight- or branched-chain alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, alkynyloxy, alkoxyalkyloxy or alkoxyalkyl group; a cycloalkyl group or a cycloalkenyl group containing one or two double bonds, which cycloalkyl and cycloalkenyl groups can be substituted by one or more alkyl groups; a cycloalkylalkyl, benzocycloalkylalkyl, tetrahydrofuryl, tetrahydrofurfuryl or tetrahydropyranyl group which can be substituted by one or more alkyl groups; a trifluoromethyl group; an alkyl group substituted by one or more halogen atoms or by one or more cyano, hydroxy, acyloxy, alkoxy, trifluoromethyl or oxo-groups; an alkenyl group substituted by a trifluoro methyl or methoxy group; an alkynyloxy group substituted by a methoxy group; a carbalkoxy-alkyl group; a cycloalkyl-alkoxy group; a cycloalkoxy- or tetrahydrofurylalkoxy group; a phenylalkoxy, phenoxyalkyl, phenoxyalkoxy, phenoxy, phenylalkyl, phenyl, phenylalkenyl or naphthyl group, in which the aromatic ring can be substituted by one or more alkyl, alkenyl, alkoxy, hydroxy, acyloxy, nitro, trifluoromethyl, cyano, carbethoxy, alkylsulphonyl, acylamino or alkylsulphonyl-amino groups or fluorine, chlorine or bromine atoms; a hetero-aromatic ring system which can be substituted by one or more alkyl groups; a furylalkyl, thienylalkyl, indolylalkyl, furylalkoxy or thienylalkoxy group which can be substituted by one or more alkyl groups; or a phenylalkyl group, the alkyl part of which is substituted by a hydroxy, acyloxy, or alkoxy group; and R<SP>7</SP> is a straight- or branched-chain alkyl or alkenyl group, an aralkyl group, a cycloalkyl group, or a cycloalkyl-alkyl group]; R<SP>3</SP>, R<SP>8</SP> and R<SP>9</SP> can be the same or different and is each a hydrogen or halogen atom or a straight- or branched-chain alkyl, alkenyl or alkoxy group or a cyano or trifluoromethyl group; R<SP>4</SP> is a straight- or branched-chain alkyl, alkenyl, alkynyl or alkoxy group; and R<SP>5</SP> is a hydrogen atom or a straight- or branched-chain alkyl or alkenyl group or a cyclo-alkyl group; and their salts may be prepared by (a) reacting an aniline derivative (3) with a carboxylic acid amide or thioamide (4) in which W is oxygen or sulphur or a salt or reactive derivative thereof especially an acetal; (b) reacting an anilide (7) with an amine R<SP>4</SP> 1 R<SP>5</SP>NH; (c) reacting an aryl isocyanate (10) or a reactive derivative thereof with an anode or thioamide (4); (d) reacting a compound (12) wherein X is halogen with an amide or thioamide (4); (e) where R<SP>4</SP> and R<SP>5</SP> are each straight or branched chain alkyl or alkenyl groups reacting an amidine (13) with an alkylating agent R<SP>10</SP>B wherein R<SP>10</SP> is straight or branched chain alkyl or alkenyl groups and B is a reactive ester group or a halogen atom; (f) reacting an aminophenyl amidine (16) with an acylating or sulphonating agent Y-Z wherein Y is a reactive ester group or a halogen atom and Z is -COR<SP>6</SP> or -SO 2 R<SP>7</SP>. N - (4 - Aminophenyl) - N<SP>1</SP>,N<SP>1</SP> dimethylacetamidine may be prepared y catalytic hydrogenation of N-(4-nitrophenyl)-N<SP>1</SP>,N<SP>1</SP>-dimethylacetamidine. N - (4 - Aminophenyl) - N<SP>1</SP> - methyl - N<SP>1</SP>- methoxyacetamidine is obtained by converting p - nitro acetanilide to N - (p - nitrophenyl)- acetimide chloride using phosphorus pentachloride and this acetimide is reacted with N,O-dimethylhydroxylamine to give N - (4 - nitrophenyl) - N<SP>1</SP> - methyl - N<SP>1</SP> - methoxyacetamidine which is catalytically reduced to the required intermediate. N - (4 - Acetaminophenyl) - acetamidine may be prepared by reaction of (a) 4-acetaminophenyl-acetiminoethyl ether with ammonia; (b) 4-aminoacetanilide with acetiminoethyl ether; or (c) 4-aminoacetanilide with acetonitrile in the presence of AlCl 3 . Other starting materials of substituted 4- amino anilines, and 4-nitro phenyl amidines are known compounds or may be prepared by methods known in the art. Pharmaceutical compositions of the compounds (1) are parasiticides especially antihelminths when administered orally or parenterally alone or with the usual excipients.