| 摘要 |
1,272,974. 12 - Substituted 11,12 - dihydro- 6H -dibenz[b,f][1,4]oxazocines. E. R. SQUIBB & SONS Inc. 30 April, 1969 [17 May, 1968], No. 21993/69. Heading C2C. Novel compounds I (including acid addition salts thereof) wherein R 1 is H or halogen, R 2 is H, halogen, trihalomethyl, alkoxy, trihalomethoxy, trihalomethylmercapto, alkyl, alkanoyl or N,N- dialkylsulphamoyl, R 3 and R 4 are H, alkyl, alkoxy, omega hydroxy-alkyl or together with the attached N comprise a 5-, 6- or 7- membered heterocycle which may be substituted to give a substituted heterocycle of less than 21 atoms excluding hydrogen and n is 1, 2, 3 or 4, are made: (a) by treating a compound II (prepared by alkylation of the corresponding 12-unsubstituted compound) with sodium borohydride in methanol or with lithium aluminium hydride in an aprotic solvent; (b) by treating a compound III (prepared by cyclization of the corresponding amino-carboxylic acid) with sodium borohydride or lithium aluminium hydride to afford a compound IV which is subsequently reacted with an alkali or alkaline earth metal hydride or metal-alkyl in an aprotic solvent and then either with an aminoalkyl halide to afford I or with a haloalkylene halide to afford a compound VI wherein X is Cl or Br and m is 2, 3 or 4 which is then treated with ammonia or an appropriate amine to afford I; (c) by reacting a compound VII {prepared by interaction of IV and a haloacyl halide of formula X(CH 2 ) r COX where r is 1, 2 or 3} with ammonia or an amine to afford a compound VIII which in turn is reacted with sodium borohydride or lithium aluminium hydride to afford I wherein lower alkylene is -(CH 2 ) m -; (d) a compound VII is first reduced to a compound VI which is thereafter reacted with ammonia or an amine; or (e) by the interaction of a compound IV with an acyl halide, (R 3 ) 2 N(CH 2 ),COX to afford VIII which is reduced as in (C). o - (o - Aminophenoxy - methyl) - benzoic acid is obtained by hydrogenating the corresponding nitro compound which in turn is derived from the corresponding methyl ester utilizing hydrolysis ; the ester is obtained by the interaction of sodium o-nitrophenolate and methyl 2-chloromethylbenzoate. Pharmaceutical preparations useful as an antihistamine, e.g. for alleviating allergies and for suppressing auricular and ventricular arrhythmias contain I as active ingredient; administration is orally or parenterally. |
