Patent GB-1086441-A (GB)
Title: Amidoximes, amidines and their acid addition salts, and preparation thereof
IPC: C07D223/28
Filed: 1965-01-08
Abstract: Compounds of the formula <FORM:1086441/C2/1> wherein Ar is a bicyclic aromatic N-heterocyclic radical having fused 5- and 6-membered rings and containing 2 or 3 N atoms which can be in any position of the two rings, indolinyl; pyrrolyl; pyrazolyl; imidazolyl; phenothiazinyl; 5 - (10,11 - dihydro - 5H - dibenz[b,f]azepinyl; 5 - (dibenzo[a,d][1,4] - cyclopentadienyl) or 1,2,3,4 - tetrahydro - a  - carbazolyl; R1 is 1, 2 or 3 H or halogen atoms or lower alkyl, lower alkoxy, lower alkylmercapto, lower alkylsulphinyl, lower alkylsulphonyl, nitro, CF3, methylenedioxy, benzyloxy, benzyl, isonitrosomethyl or dilower alkylaminomethyl radicals; R2 is H, lower alkyl, lower alkanoyl, or OH; R3 is H or lower alkyl; Z is H or OR4 where R4 is H, lower alkanoyl, benzoyl, lower alkyl or benzyl, R2 excluding OH when Z is H; Y is CmHm where m is 0 or 1-5 or hydroxy lower alkylene of 1-5 C atoms and having the OH group attached to the C atom adjacent to the amidoxime group and n is 1 or 2, are prepared (a) by reacting a compound of the formula R1-(Ar)-(Y1-CN)n with hydroxylamine in the presence of a base (to give a compound I wherein Z = OR4 and R2, R3 and R4 are H) or (b) by reacting a lower alkylamine, di-lower alkylamine or an N-lower alkylhydroxylamine with a compound <FORM:1086441/C2/2> (to give a compound I wherein Z = OR4, R2 is lower alkyl or OH; R3 = H or lower alkyl; R4 is H, lower alkanoyl, benzoyl, lower alkyl or benzyl; and Y1 is CmH2m) and if desired, converting a compound obtained wherein R2 is H or lower alkyl; and R4 is H to its alkali metal salt and reacting said salt with a lower alkyl or benzyl halide (to give the compound I where Z = OR4, R4 is lower alkyl or benzyl) or reacting a compound wherein R2 is H and R4 is lower alkyl or benzyl with a lower alkanoyl halide (to give the compound I wherein Z = OR4 and R2 is lower alkanoyl) or dibenzylating the compound where R4 is benzyl (to give the compound I where Z = OR4 and R4 is H), or reacting a compound obtained where R2 and R3 are H or lower alkyl and R4 is H with a lower alkanoic or benzoic anhydride (to give compounds I wherein Z = OR4 and R4 is lower alkanoyl or benzoyl); or (c) by reacting a compound II with a lower alkanol and the resulting imino ester with anhydrous ammonia or an amine HNR2R3 (to give a compound I wherein Z = H and R2 and R3 are H or lower alkyl) and if desired reacting the compound wherein R2 is H with a lower alkanoylating agent (to give I wherein Z = H and R2 is lower alkanoyl).  In the foregoing definitions "lower" indicates 1-4 carbon atoms in the groups so qualified and when R4 is benzyl or a benzoyl group the benzene ring may be substituted by 1, 2 or 3 atoms or groups provided that these do not take part in the reaction. Compounds of Formula II are prepared by direct alkylation of an acyl nucleus either by a haloalkanonitrile or an acrylonitrile or by reduction of a 3-arylacrylonitrile in turn prepared from an aryl carboxaldehyde and cyanoacetic acid followed by decarboxylation of the 3-aryl-2-cyanoacrylic acid.  Pharmaceutical compositions useful as hypotensive agents comprise the compounds of Formula I and a carrier therefor.  The compositions may be in a form for oral or parenteral administration.