GB1490671A - Perhalo-alkylamidines - Google Patents

Abstract

1490671 Amidines MERCK & CO Inc 12 Jan 1976 [15 Jan 1975 10 Nov 1975] 01016/76 Heading C2C Novel compounds of formula in which R is a perhalogenated alkyl group; R 1 is hydrogen, alkyl, alkanoyl, phenylcarbamoyl or alkoxalyl; R 2 is hydrogen, alkyl or alkanoyl; and R 3 is (a) alkyl, phenyl-alkyl, alkenyl, alkynyl, cycloalkyl or cycloalkenyl, which groups are substituted with one or more of hydroxy, hydroxyalkyl, alkoxy, alkylthio, alkanoyloxy, alkanoylamino, phenyl, hydroxyphenyl, alkoxyphenyl, phenoxy, phenylsulphinyl, naphthylsulphinyl, cycloalkyl, alkylphenyl, alkenylphenyl, phenylcycloalkyl or halo; (b) phenyl-alkyl substituted with perhaloalkylamidinoalkyl; (c) a heterocyclic group of from 5 to 7 members, joined to the amidine nitrogen through an alkyl group and containing one or two heteroatoms selected from oxygen and nitrogen; or (d) a benzoheterocyclic group optionally substituted with alkyl, alkoxy or benzoyl and in which the benzo residue is fused to a heterocyclic ring of from 5 to 7 members with one or two heteroatoms selected from oxygen and nitrogen; or R 2 and R 3 or R 1 and R 3 are joined to form a heterocyclic ring containing from 5 to 7 members including the two amidine nitrogen atoms; which heterocyclic ring is substituted with hydroxy, alkoxy, phenyl, halo, alkylbenzo, alkoxybenzo; and the non-toxic, pharmaceutically acceptable salts thereof and glycosides of any reactive proton in groups such as amino or hydroxy are prepared (a) by alkylation or acylation of or for cyclic compounds by RCN + an optionally substituted diamine. The intermediate amidine is prepared by RCN + HNR 2 R 3 . The following amines are also prepared for use in the above 2,3-dichloro and 2,3-dimethyl-4- hydroxybenzylamine by reduction of the corresponding benzaldehyde oxime which is prepared from the aldehyde; 3-(2-allylphenoxy)-2-hydroxypropylamine; 3,4 - bis - aminomethyltoluene; 3 - aminomethyl - 1 - benzoylindole from N - (3 - indolylmethyl) - t - butylcarbamate prepared from 3-aminomethylindole and t - butyl 2,4,5 - trichlorophenylcarbonate; 4,#- diacetoxyphenethylamine; 3 - (4 - acetamidophenoxy - 2 - hydroxypropylamine from N - [3- (4 - acetamidophenoxy) - 2 - hydroxypropyl]- benzylamine prepared from 1 - (4 - acetamidophenoxy) - 2,3 - epoxypropane and benzylamine; 3 - aminoethyl - 5 - methoxyindole; 2- aminoethyl - 2 - naphthylsulphoxide from 2 - (2 aminoethylthio)-naphthalene obtained from N- [2 - (naphthylthioethyl]phthalimide prepared from 2-bromoethylphthalimide and 2-naphthylthiol. Pharmaceutical compositions in conventional form for oral or parenteral administration having cardiotonic activity comprise an above novel compound and a carrier or diluent.