GB1152885A - Indazole-3-yl-Oxyalkanoic Acids and process for the preparation thereof - Google Patents

Abstract

1,152,885. lndazol-3-yl-oxyalkanoic acids. AZIENDE CHIMICHE RIUNITE ANGELINI FRANCESCO. 25 May, 1967 [29 Aug., 1966; 21 April, 1967], No. 24384/67. Heading C2C. Novel indazol-3-yl-oxyalkanoic acids of the general formula wherein X is hydrogen, chlorine, methoxy, nitro, amino or acetamino, R is hydrogen, phenyl or benzyl; phenyl and benzyl may be substituted with methyl, methoxy, halogen, trifluoromethyl or dimethylsulphamide and n is 1 or 2, and the non-toxic salts thereof with metals or organic bases and, when X=NH 2 the acid addition salts with organic and inorganic acids are prepared by reacting an alkali metal salt of the corresponding 3-oxy-indazole with a halogen compound of the formula Halogen-(CH 2 ) n -CR<SP>1</SP>, wherein R<SP>1</SP> is carboxy, carbethoxy, nitrile or carboxyamide, and where R<SP>1</SP> is other than carboxy, hydrolysing the resulting ester, nitrile or amide. Compounds in which n is 2 may also be prepared by reacting the sodium salt of the appropriate 3-oxy-indazole with propiolactone. In addition, benzyl and substituted benzyl derivatives may be obtained by reacting the corresponding unsubstituted indazole-3-ylalkanoic acids with the appropriate benzyl halide in an aqueous alkaline medium, and the 5 - nitro - 5 - amino- and 5 - acetamino - derivatives by nitrating the corresponding compound, wherein X is hydrogen, followed by reduction and acylation with acetic acid, if desired. Ethyl (1 - m - chlorobenzyl - indazol - 3 - one-2- yl) acetate and (1-p-chlorobenzyl-indazol-3-one- 2-yl) acetic acid are obtained as by-products by reacting an alkali metal salt of the appropriate 3-oxy-indazole with ethyl bromoacetal and bromoacetic acid respectively. (1-m-chlorobenzyl - indazol - 3 - one - 2 - yl) acetic acid is made by hydrolysing the above ester. The amide and nitrile of (1-benzyl-indazol- 3-yl) acetic acid and ethyl (1-m-chlorobenzylindazol-3-yl) acetate are prepared by reacting an alkali metal salt of the corresponding 3-oxyindazole with chloroacetamide, chloroacetonitrile and ethyl bromoacetate respectively. 1 - (2,6 - Dimethyl - 3 - dimethylsulphamoyl) phenyl-3-oxy-indazole is made by treating with zinc dust an acetic acid solution of N-(2,6- dimethyl - 3 - limethylsulphamoyl) phenyl - N- nitroso-anthranilic acid, resulting from the nitrosation of the corresponding substituted anthranilic acid. The sodium salt of 1-m-chlorobenzyl-3-oxyindazole is obtained by reacting 1-m-chlorobenzyl-3-oxy-indazole with sodium methoxide. The following starting materials are stated to be novel: 1-m-chlorophenyl-, 1-trifluoromethylphenyl-, 1-p-fluorophenyl-, and 1-mbromophenyl- 3 -oxy-indazoles. Therapeutic compositions, having anti-inflammatory activity contain the above novel indazole-3-yl-alkenoic acids or non-toxic salts thereof as the active ingredient.