Patent GB-1308259-A (GB)
Title: Phenethylamine derivatives and a process for the manufacture thereof
IPC: C07F5/04
Filed: 1971-10-29
Abstract: 1308259 3,4-Dihydroxyphenethylamine derivatives; borax complex F HOFFMANN-LA ROCHE & CO AG 29 Oct 1971 [30 Oct 1970] 50336/71 Headings C2B and C2C Novel compounds of Formula I   wherein R 1  represents a hydrogen atom, an alkanoyl group which may be substituted by alkoxy or by phenyl which may, in turn, be alkoxy- or halo-substituted, a benzoyl group which may be alkoxy or halo-substituted, an alkenoyl group, an alkoxycarbonyl group which may be phenyl-substituted, an aminocarbonyl group which may be alkyl-substituted or the o-nitrophenylthio group and R 2  represents an alkanoyl group containing at least 4 carbon atoms which may be substituted by alkoxy or by phenyl which may, in turn, be alkoxy- or halo-substituted, a benzoyl group which may be alkoxy- or halo-substituted, an alkenoyl or alkoxycarbonyl group, an aminocarbonyl group which may be alkyl-substituted, an alkylsulphonyl group, an alkyl group which is substituted by alkenyl, alkynyl, alkoxyalkyl, cyano, carboxy, alkoxycarbonyl (which may be alkenyl-, alkynyl- or phenyl-substituted) or aminocarbonyl (which may be alkyl-substituted), provided that R 1  is different from R 2  and salts thereof, are prepared by one of the following methods; (A) a compound of Formula II wherein R<SP>1</SP> 1  has any value of R 1  except H is reacted with an acyl halide, acid anhydride or acid azide to furnish the group R 2  except where R 2  is carboxy alkyl or (B) reducing a compound of formula wherein R 2  has the significance given earlier and R 3  represents the 2-nitrovinyl or cyanomethyl group or a group of the formulµ in which R<SP>11</SP> 1  has any of the values accorded to R 1  hereinbefore except o - nitrophenylthio, benzyloxycarbonyl or t-alkoxycarbonyl and R 4  represents a hydroxy, lower alkoxy or phenylamino group, provided that when R 3  represents a 2-nitrovinyl or cyanomethyl group R 2  represents other than a halo-substituted phenylalkanoyl or halo-substituted benzoyl group, when R 3  represents the group (a) R 2  represents an alkyl group which is substituted by alkenyl, alkynyl, alkoxyalkyl, cyano, carboxy, alkoxycarbonyl (which may be alkenyl-, alkynyl- or phenyl-substituted) or aminocarbonyl (which may be alkyl-substituted), when R 3  represents the group (b) R 2  represents other than a cyanosubstituted alkyl group and when R 3  represents the group (c) R 2  represents other than an alkenyl-, alkynyl-, or cyano-substituted alkyl group, or (C) hydrolysing a compound of formula wherein R<SP>1</SP> 2  denotes any value of R 2  other than carboxyalkyl or treating it with an alkanol which may be phenyl-substituted or with ammonia or an alkylamine or dialkylamine, or (D) reacting a compound of formula or a salt thereof with an acyl halide, acid anhydride or acid azide to furnish the group R<SP>1</SP> 1  and, if desired, cleaving off a benzyloxycarbonyl group brand to the nitrogen atom of a compound of Formula I obtained by reduction or by treatment with hydrogen bromide or trifluoroacetic acid or cleaving- off a t-alkoxycarbonyl group or the o-nitrophenylthio group bound to the nitrogen atom of a compound of Formula I obtained by treatment with an acidic agent or cleaving off an acid group R 1  from a compound of Formula I obtained in which R 2  represents an alkyl group which is substituted by alkenyl, alkynyl, alkoxyalkyl, cyano, carboxy, alkoxycarbonyl (which may be alkenyl-, alkynyl- or phenyl-substituted) or aminocarbonyl (which may be alkyl-substituted) by hydrolysis, and, also if desired, converting a product obtained into a salt. Intermediates of Formula II above wherein R<SP>1</SP> 1  is benzyloxycarbonyl, t-butoxycarbonyl or acetyl are prepared by reacting carbobenzoxychloride, t-butoxycarbonyl hydrazide or acetic anhydride respectively with an aqueous alkaline solution of a complex of borax and 3,4-dihydroxyphenethylamine in which the two hydroxy groups are in effect esterified by the borax, the complex being formed by adding borax to an aqueous solution of dopamine hydrobromide and adjusting to pH 10 with sodium hydroxide. Pharmaceutical compositions in conventional forms for oral or parenteral administration and having hypotensive antipyretic and anti- Parkinson activity comprise an above novel compound or salt and a pharmaceutical carrier.