Patent GB-1468156-A (GB)
Title: Phenylethylamine derivatives
IPC: C07C239/00
Filed: 1973-07-19
Abstract: 1468156 Phenylethylamine derivatives IMPERIAL CHEMICAL INDUSTRIES Ltd 1 July 1974 [19 July 1973] 34465/73 Heading C2C [Also in Division A5] The invention comprises phenylethylamine derivatives of the formula wherein A is C 1-6  alkylene; Q is -CO- or -CH(OH)-; R<SP>1</SP> is C 1-6  alkyl or, C 3-6  cycloalkyl or a phenyl radical -C 6 H 3 R<SP>12</SP>R<SP>13</SP>, wherein R<SP>2</SP>, R<SP>3</SP>, R<SP>12</SP> and R<SP>13</SP> each are H, halogen, OH, NH 2 , CH 2 OH, C 1-6  alkoxy, C 1-6  alkyl, C 1-6  (carboxylic acyl) amino, C 1-6  alkanesulphonamido, or an aryl radical of up to 12 carbon atoms; X is -CONH-, -NHCO- or -NHSO 2 -; and Y is a direct link, C 1-6  alkyleneoxy, imino, imino- C 1-6  alkyleneoxy, imino-C 1-5  alkylenecarbonyloxy or -NR<SP>1</SP>, wherein R<SP>1</SP> is as defined above- and acid addition salts thereof and their preparation. The compounds are prepared by assembling in sequence (i) 2-phenylethyl radicals of the formula wherein Q<SP>1</SP> is -CO- or -CH(OR<SP>5</SP>), wherein R<SP>4</SP> and R<SP>6</SP> each H or protecting group; (ii) imino radicals of the formula -NR<SP>6</SP>-, wherein R<SP>6</SP> is H or protecting group; (iii) radicals of the formula A-X<SP>1</SP> and (iv) radicals of the formula -X<SP>2</SP>-Y-R<SP>1</SP>, wherein X<SP>1</SP> and X<SP>2</SP> together form X; whereafter if one or more of R<SP>4</SP>, R<SP>5</SP> and R<SP>6</SP> are protecting groups, these are removed, whereafter racemic phenylethylamine derivatives may be resolved and free bases converted to acid addition salts. Compounds in which Q is -CH(OH)- may be obtained by reacting compounds of the formula wherein R<SP>4</SP> is H or benzyl and 2 is halogen, with amines of the formula wherein R<SP>7</SP> is H or benzyl, followed by reduction of the -CO- group with alkali metal borohydrides or by catalytic hydrogenation, and either the simultaneous or subsequent conversion by catalytic hydrogenolysis of compounds, if appropriate R<SP>4</SP> and/or R<SP>7</SP> is benzyl; or reacting compounds of the formula or hydrates thereof with amines of the formula in the presence of hydrogen and hydrogenation catalysts; or for those compounds wherein X is -NHCO- or -NHSO 2 -, reacting compounds of the formula wherein R<SP>4</SP> and R<SP>6</SP> are benzyl, with compounds of the formulae wherein Z<SP>1</SP> is H or alkoxy, and hydrogenating the resulting products. The following intermediates are also prepared 1 - p - benzyloxyphenyl - 2 - [N - benzyl - N - (2- isobutyramido - ethyl)amino]ethanol, N - [2- (N - benzyl - 2 - m - benzyloxyphenyl - 2 - oxoethylamino)ethyl]isobutyramide; N - [2 - (N- benzyl - 2 - m - benzyloxyphenyl - 2 - hydroxyethylamino)ethyl]isobutyramido; o - benzyloxyacetophenone; o - benzyloxyphenacylbromide; 4 - benzyloxy - 3 - methylacetophenone; 4- benzyloxy - 3 - methylphenacylbromide; the salt of N - benzyl - N - (2 - isobutyramidoethyl)- amine with N - 2 - [N - benzyl - N - {2 - (4- benzyloxy - 3 - methanesulphonamidophenyl)- 2 - oxoethyl}amino]ethylisobutyramide; 1 - (4- benzyloxy - 3 - ethoxycarbonylphenyl) - 2 - [N- benzyl - N - (# - 3 - phenylureidoethyl)amino]- ethanol oxalate; 1 - (4 - benzyloxy - 3 - hydroxymethylphenyl) - 2 - [N - benzyl - N - (# - 3- phenylureidoethyl)amino]ethanol; 1 - (4 - benzyloxy - 3 - ethoxycarbonylphenyl) - 2 - [N- benzyl - N - (2 - isobutyramidoethyl)amino]- ethanol; 1 - (4 - benzyloxy - 3 - hydroxymethylphenyl) - 2 - (N - benzyl - N - (2 - isobutyramidoethyl)amino]ethanol; 1 - p - benzyloxyphenyl- 2 - [Cl - methyl - 2 - phenylacetamidoethyl) - amino]ethanol; N - (2 - oxo - propyl)phenylacetamide; 1 - p - benzyloxyphenyl - 2 - [(# - 3- isopropylureaidoethyl)amino]ethanol; 1 - pbenzyloxy - phenyl - 2 - [N - benzyl - N - (2- aminoethyl)amino]ethanol; and 1 - p - benzyloxyphenyl - 2 - [N - benzyl - N - (2 - phenylacetamidoethyl)amino]ethanol.