Patent GB-1145278-A (GB)
Title: Amidine derivatives, processes for their preparation, and compositions incorporating them
Inventor: HODSON HAROLD FRANCIS
IPC: C07D333/16
Filed: 1965-12-23
Abstract: 1,145,278. Amidines; substituted amines and nitriles. WELLCOME FOUNDATION Ltd. 13 Dec., 1966 [23 Dec., 1965], No. 54489/65. Heading C2C. Novel amidines of the formula (in which one of X<SP>1</SP> and X<SP>2</SP> is a phenyl group substituted in at least one position by a group X<SP>3</SP> or a group X<SP>3</SP>O, X<SP>3</SP> being a phenyl or phenylalkyl group, each of the phenyl rings in the whole group being optionally further substituted with substituent(s) which are each a halogen atom or an alkyl, alkoxy, hydroxy, alkylthio, alkylsulphinyl or alkylsulphonyl group; the other of X<SP>1</SP> and X<SP>2</SP> is an X<SP>3</SP>-substituted or X<SP>3</SP>O-substituted phenyl group as defined above, or a phenyl or thien-2-yl ring optionally substituted with substituents which are each a halogen atom or an alkyl, alkoxy, hydroxy, alkylthio, alkylsulphinyl or alkylsulphonyl group; A<SP>1</SP> is a straight- or branchedchain alkylene linkage containing 2 to 6 carbon atoms and one or two divalent atoms which are each an oxygen or sulphur atom, provided that there are at least two carbon atoms between the divalent atom and the -NH- group and between the two divalent atoms; and A<SP>2</SP> is a straight- or branched-chain alkylene linkage containing from one to four carbon atoms; while, in the above definitions of X<SP>1</SP> and X<SP>2</SP>, the " alkyl " and " alkoxy " groups each contain from one to four carbon atoms; and acidaddition salts thereof; are prepared by (a) reacting ammonia with an imidocarbonyl compound of formula in which Y is a halogen atom or an alkylthio, mercapto or alkoxy group, or (b) reacting an amine of formula X<SP>1</SP>.A<SP>1</SP>.NH 2  with an imidocarbonyl compound of formula in which Y<SP>2</SP> is a hydrogen atom and Y<SP>3</SP> is an amino, mercapto, alkylthio or alkoxy group or Y<SP>2</SP> and Y<SP>3</SP> together form a bond, or (c) reacting an imidocarbonyl carbonyl of the formula (the two forms being tautomeric), with a reducing agent. 2 - (2<SP>1 </SP>- Benzyloxyphenoxy) - propylamine is prepared by reacting 2-chloropropionitrile with 2-benzyloxyphenol to give 2-(2<SP>1</SP>-benzyloxyphenoxy) propionitrile and reducing this with lithium aluminium hydride. 2 - (3<SP>1</SP> - Benzyloxyphenoxy) propylamine, 2 - (3<SP>1</SP> - phenylphenoxy) propylamine, 2 - (41 - benzyloxyphenoxy) propylamine and 2 - (3<SP>1 </SP>- phenoxyphenoxy) propylamine are similarly prepared via the corresponding nitrile intermediates. 2 - (31 - Benzyloxybenzyloxy) propylamine is prepared by reacting 2-aminopropanol with 3-benzyloxybenzyl chloride. 3 - Benzyloxyphenylacetamidine p-toluenesulphonate is prepared by reacting sodium cyanide with 3-benzyloxybenzyl chloride to give 3-benzyloxyphenylacetonitrile and treating this successively with ethanolic hydrogen chloride, ethanolic ammonia, and sodium p-toluenesulphonate. 3,4 - Dimethylphenyl (thioacetamide) is prepared by reacting hydrogen sulphide with 3,4 - dimethylphenylacetonitrile. 3 - Methylphenyl (thioacetamide) is similarly prepared. Pharmaceutical compositions, which antagonize the effect of 5-hydroxytryptamine, comprise a compound of the invention together with a carrier. The compositions may be in a form suitable for oral, parenteral, vaginal or rectal administration.