Patent GB-1392542-A (GB)
Title: Diazepine derivatives
IPC: C07C45/63
Filed: 1972-05-12
Abstract: 1392542 1,3 - Dihydro - 5 - phenyl - 2H- thieno[2,3-e][1,4]diazepin- 2 - ones F HOFFMANN-LA ROCHE & CO AG 12 May 1972 [14 May 1971] 22369/72 Heading C2C Novel 1,3 - dihydro - 5 - phenyl - 2H - thieno- [2,3-e][1,4]diazepin- 2 - ones of the general formula wherein R 1  is a halogen atom or nitro group, R 2  is a hydrogen atom or -CH 2 X group, in which X is a hydrogen atom or an alkyl, alkenyl or cycloalkyl group containing at most 4 carbon atoms, a hydroxymethyl or methoxy group or a dialkylaminomethyl group of at most 5 carbon atoms, and R 3  is an o-halo-, o-trifluoromethyl- or o,o<SP>1</SP> - dihalo - phenyl group or, when R 1  is a halogen atom, an onitrophenyl group, and their salts are prepared (a) by halogenating or nitrating a 1,3 - dihydro - 5 - phenyl - 2H- thieno- [2,3-e][1,4]diazepin- 2 - one of the general formula above wherein R 1  is a hydrogen atom and R 3  may be an o-nitrophenyl group in the case of halogenation, at the 7-position; (b) by cyclizing a 2-aminoacetylamino-3-benzoylthiophene of the general formula and (c) when R 2  is a -CH 2 X group, by substituting the corresponding compound in which R 2  is a hydrogen atom with the desired group at the 1-position; followed optionally by salification of the product. 1,3 - Dihydro - 5 - phenyl - 2H - thieno[2,3-e]- [1,4]diazepin - 2 - ones of the first general formula above wherein R 1  is a hydrogen atom, and R 3  is an o-halophenyl, o-trifluoromethylphenyl, o,o<SP>1</SP>-dihalophenyl or onitrophenyl group, which are novel provided that whenR 2 is a hydrogen atom or -CH 2 X, in which X is a hydrogen atom or a C 1-3  alkyl group, R 3  is not an o-halophenyl or o-trifluoromethylphenyl group, are prepared (d) when R<SP>2</SP> is a -CH 2 X group, by a process analogous to (c) above; and (e) by a process analogous to (b) above. 2 - Aminoacetylamino - 3 - benzoyl - thiophenes of the second general formula above wherein R 1  is a hydrogen or halogen atom or a nitro group are prepared (f) when R 2  is a hydrogen atom, by reacting a 2-chloroacetylamino-3-benzoyl-thiophene of the general formula with sodium iodide and reacting the resulting 2- iodo - acetylamino - 3 - benzoyl - thiophene of the general formula with ammonia; and (g) when R 1  is a hydrogen atom and R 2  is a -CH 2 X group, by reacting a phenacyl cyanide of the general formula R 3 COCH 2 CN with 2,5-dihydroxy- 1 ,4-dithiane, acetylating the resulting 2-amino-3-benzoylthiophene of the general formula substituting the resulting 2-acetylamino-3-benzoyl - thiophene of the general formula at the nitrogen atom with a-CH 2 X group, acid hydrolysing the resulting 2-acetyl-amino-3-benzoyl-thiophene of the general formula and reacting the resulting 2-amino-3-benzoylthiophene with carbobenzoxyglycyl chloride in the presence of a base, followed by treatment with HBr in glacial acetic acid. 2 - Chloroacetylamino - 3 - benzoyl - thiophenes of the third general formula above are prepared (h) when R 1  is a halogen atom or nitro group, by halogenating or nitrating the corresponding compound in which R 1  is a hydrogen atom; and (i) when R 1  is a hydrogen atom, by chloroacetylating a 2-amino-3-benzoyl-thiophene of the sixth general formula above. Phenacyl cyanides of the fifth general formula above are prepared (j) by treating a benzonitrile of the general formula R 3 -CN with acetonitrile and sodium and hydrolysing the resulting imine of the general formula or (k) by brominating an acetophenone of the general formula R 3 COCH 3  and treating the resulting phenacyl bromide with aqueous-alcoholic potassium cyanide. Pharmaceutical compositions having musclerelaxant and sedative activity comprise, as active ingredient, a 1,3-dihydro-5-phenyl-2H- thieno[2,3-e][1,4]diazepin-2-one of the first general formula above wherein R 1  is a halogen atom or nitro group of a pharmaceutically utilizable acid addition salt thereof, in association with a compatible pharmaceutical carrier. Reference has been directed by the Comptroller to Specification 1,291,684.