Patent GB-1414207-A (GB)
Title: Benzo b thiophene derivatives their preparation and use as pharmaceuticals
IPC: C07D333/70
Filed: 1973-11-27
Abstract: 1414207 Benzo-(b)-thiophenes, their preparation and use in pharmaceutical compositions WARNER-LAMBERT CO 27 Nov 1973 [27 Nov 1972] 54845/73 Heading C2C Benzo-(b)-thiophenes of the formula wherein Y is a hydrogen or halogen atom, A is a hydrogen atom or a phenyl radical which may be substituted by a halogen atom or a C 1-6  alkoxy radical, B is a radical of the formula OR<SP>1</SP> or NR<SP>2</SP>R<SP>3</SP>, wherein R<SP>1</SP> is an alkyl radical containing up to 5 carbon atoms which may be substituted by hydroxyl, C 1-6  alkoxy or phenoxy radicals, or R<SP>1</SP> is a substituted-unsubstituted cycloalkyl or phenyl radical, and R<SP>2</SP> and R<SP>3</SP>, which may be the same or different, are, if the same, hydrogen atoms or alkyl radicals containing up to 5 carbon atoms whch may be substituted by hydroxyl, C 1-6  alkoxy; phenoxy, dialkylamino or phenyl radicals or, if R<SP>2</SP> is a hydrogen atom, R<SP>3</SP> may be a hydroxyl group or an amino group, which may be substituted by dialkyl, alkylene alkylidene, phenyl, acyloxyalkyl or acyl radicals, or R<SP>3</SP> may be a C 1-6  alkyl group which may be substituted by hydroxy, C 1-6  alkoxy, phenyl, phenoxy, dialkylamino, pyrrolidino, piperidino or morpholino radicals, or R<SP>3</SP> may be a cycloalkyl or phenyl radical optionally substituted by halogen atoms or C 1-6  alkoxy radicals, or R<SP>2</SP> and R<SP>3</SP>, together with the nitrogen atoms to which they are attached, form an aziridine, pyrrolidine, piperidine, morpholine or piperazine ring, which may be substituted by C 1-6  alkyl, hydroxyalkyl, phenylalkyl, phenyl or acetyl radicals, or A and B, together with the -C=N- group, form an unsubstituted or substituted 5-, 6- or 7-membered heterocyclic ring system which can contain more than one hetero atom, and the physiologically acceptable inorganic and organic acid addition salts and the quaternary ammonium salts thereof, may be obtained (a) by reacting a thiosalicylic acid derivative of the formula in which R<SP>4</SP> is a hydrogen atom or a C 1-6  alkyl radical, with an imidate or amidine of the formula  or a salt thereof, wherein Hal is a halogen atom, (b) wherein B is an NR<SP>2</SP>R<SP>3</SP> radical, by reacting a compound of Formula (I) in which B is an OR<SP>1</SP> radical with an amine of the formula HNR<SP>1</SP>R<SP>3</SP>, or (c) wherein B is an OR<SP>1</SP> radical, by transesterifying a compound of Formula (I) in which B is an OR<SP>1</SP> radical, with an appropriate alcohol to replace the OR<SP>1</SP> radical by a different OR<SP>1</SP> radical; the product may be quaternized or reacted with an organic or inorganic acid to give an acid addition salt. Reaction (a) may be effected at 20-150 C. in the presence of an alkali metal or alkali metal hydride, alkoxide, hydroxide or carbonate and optionally in the presence of a solvent, and the imidate or amidine starting material can be used in situ in solutions obtained during their preparation. Reaction (b) may be carried out in a solvent or in excess of the amine at a temperature of 0-150 C. The products possess analgesic, antipyretic and anti-inflammatory properties and they may be formulated into pharmaceutical compositions in a known manner.