GB1273653A - Derivatives of phenolic amino alcohols - Google Patents

Abstract

1,273,653. Derivatives of phenolic amino alcohols. MERCK & CO. Inc. 6 July, 1970 [10 July, 1969], No. 32589/70. Heading C2C. Novel compounds of Formula I wherein R<SP>1</SP> is H or -C : O.R or where R<SP>4</SP> is a hydrogen atom, an alkyl, cycloalkyi, alkenyl, cycloalkenyl, alkoxy, phenyl or benzyl radical, a substituted phenyl or benzyl in which the substituent(s) is/are halogen, C 1-6 alkyl, C 1-6 perfluoroalkyl, C 1-6 alkoxy, hydroxy, amino, alkylamino, dialkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, nitro, sulfamoyl, alkylsulfamoyl or phenyl, a substituted alkyl radical in which the substituent(s) is/are halogen, aryl, hydroxy, amino, C 1-6 alkoxy, carboxy or esterified carboxy, or a heterocyclic radical that is optionally substituted by C 1-6 alkyl, halogen or methoxy, and R<SP>5</SP> is a hydrogen atom or an alkyl or phenyl radical or a substituted phenyl radical in which the substituent(s) is/are halogen, C 1-6 alkyl, C 1-6 perfluoroalkyl, C 1-6 alkoxy, hydroxy, amino, alkylamino, dialkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, nitro, sulfamoyl, alkylsulfamoyl or phenyl or R<SP>4</SP> and R<SP>5</SP> are combined to form a saturated or unsaturated unsubstituted or phenyl-substituted alicyclic or heterocyclic ring; R<SP>6</SP> is a hydrogen atom or an alkyl or phenyl radical and n is 0 when R<SP>4</SP> or R<SP>5</SP> is joined to the C atom by a double bond, n otherwise being 1; X is a hydrogen or halogen atom, a hydroxy, alkoxy, alkyl or phenyl radical or a radical of formula R<SP>3</SP> is a hydrogen atom or a C 1-6 alkyl radical and each R<SP>2</SP> is a hydrogen atom, an alkyl, phenyl, benzyl, heterocyclic, cycloalkyl, alkenyl or cycloalkenyl radical, a substituted phenyl or benzyl in which the substituent(s) is/are halogen, C 1-6 alkyl, C 1-6 perfluoroalkyl, C 1-6 alkoxy, hydroxy, amino, alkylamino, dialkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, nitro, sulfamoyl, alkylsulfamoyl or phenyl or a substituted alkyl radical in which the substituent(s) is/are halogen, aryl, hydroxy, amino, C 1-6 alkoxy, carboxy or esterified carboxy, are prepared either by rearrangement under acidic conditions of a compound of Formula II wherein Z is OH or Cl, or by reaction of an acid halide or anhydride of an acid of formula R<SP>2</SP>COOH with a compound of Formula IV wherein R<SP>7</SP> is an amino blocking group which is removed after the reaction. Intermediates of Formula II above are prepared by reaction of an alcohol of Formula XII with one equivalent of a reactive derivative of R 2 COOH optionally followed by conversion of Z when OH into Z=Cl by SOCl 2 . Threo α-(1-aminoethyl)-3-hydroxybenzyl alcohol is prepared by action of hydrogen and catalyst on threo 3-benzyloxy-α-(1-dibenzylaminoethyl)- benzyl alcohol prepared by reduction of m-benzyloxy-α-dibenzylaminopropiophenone obtained by reaction of dibenzylamine with m-benzyloxy-α- bromopropiophenone, itself or prepared by action of bromine on the unhalogenated compound. Erythro α-(1-aminoethyl)-3-methoxy-6-methylbenzyl alcohol is prepared by catalytic reduction of 3-methoxy-6-methyl-α-aminopropiophenone obtained by reduction of the corresponding amine which is prepared by rearrangement of the oxime obtained from 3-methoxy-6-methylpropiophenone prepared by reaction of propionitrile and the Grignard reagent from 2-bromo-4- methoxytoluene. Pharmaceutical compositions in conventional forms for oral or parenteral administration and having antihypertensive activity and capable of inhibiting gastric secretion comprise an above novel compound and a carrier or diluent.