Patent GB-1176701-A (GB)
Title: 0-Acyl-3-Indolyl Aliphatic Acid Derivatives and methods of making them
IPC: C07D209/26
Filed: 1967-01-03
Abstract: 1,176,701. Substituted indoles; substituted hydrazines and hydrazones. SUMITOMO CHEMICAL CO. Ltd. 3 Jan., 1967 [12 Jan., 1966; 28 April, 1966 (2); 2 May, 1966; 4 May, 1966; 21 June, 1966; 8 July, 1966 (2); 19 Aug., 1966 (2)], No. 311/67. Heading C2C. Novel indoles of the general Formula I wherein R<SP>1</SP> is an unsubstituted saturated or unsaturated aliphatic group having not more than 10 carbon atoms, R<SP>2</SP> and R<SP>3</SP> are each a hydrogen atom or an alkyl group having not more than 3 carbon atoms, R<SP>4</SP> is a hydrogen atom a carboxy group or an alkoxycarbonyl group having not more than 4 carbon atoms, R<SP>5</SP> is an alkoxy group having not more than 4 carbon atoms or a benzyloxy, tetrahydropyraryloxy, hydroxy or amino group, R<SP>6</SP> is an alkyl group having not more than 3 carbon atoms, an alkylthio group having not more than 3 carbon atoms or a hydrogen or halogen atom, m and p are each 0 or 1, and n is 0, 1, 2 or 3, are prepared by reacting either a phenyl hydrazine of the Formula II or a salt thereof or a phenyl - hydrazone of the Formula VI with a compound of the Formula III by reacting a phenylhydrazone of the Formula X with an acyl compound of the formula R<SP>1</SP>COY, to form an indolylaliphatic ester of the first formula above wherein R<SP>1</SP>, R<SP>2</SP>, R<SP>3</SP> and R<SP>6</SP> and m and n have the significance indicated above, p is 0 and R<SP>5</SP> is other than hydroxy or amino, by hydrolysing, heating or hydrogenating as required on indole of the Formula XI wherein R<SP>1</SP>, R<SP>2</SP>, R<SP>3</SP>, R<SP>6</SP>, m and n have the above significance and R<SP>7</SP> is an alkoxy of not more than 4 carbon atoms, amino or benzyloxy group, by dehydrating and, if necessary, simultaneously hydrolysing an indole of the Formula XIII wherein R<SP>1</SP>, R<SP>2</SP> and R<SP>6</SP> have the significance indicated for the first formula above and R<SP>5</SP> is an hydroxy or alkoxy group to form the corresponding indolylacetic acid, by dehydrogenating an indole of the Formula XIV wherein R<SP>1</SP>, R<SP>2</SP>, R<SP>3</SP> and R<SP>6</SP> have the significance indicated for the first formula above, to form the corresponding indolylaliphatic acid, and by reacting at a temperature of 60‹ to 200‹ C. a phenylhydrazine of the above Formula II with a dicarboxylic acid of the Formula V to form an indole of the first formula above in which n and p are O and R<SP>5</SP> represents an hydroxy group. Therapeutic compositions having anti-inflammatory, analgesic and anti-pyretic action contain as the active ingredients the novel indoles defined above. Hydrazines of the above Formula II, wherein R<SP>1</SP> is an unsubstituted saturated or unsaturated aliphatic group having not more than 10 carbon atoms and R<SP>6</SP> is an alkyl or alkylthio group having not more than 3 carbon atoms or a hydrogen or halogen atom, are prepared by reacting a phenylhydrazone with R<SP>1</SP>-CO-Y to form a phenylhydrazone of the above Formula VI wherein R 1  and R 6  have the above significance, B is the residue of an aldehyde or ketone, and Y is a halogen atom or ester residue and treating this compound with an acid. In some cases the desired hydrazine is formed direct without the intermediate formation of the hydrazone.