GB1393600A - 6,7-dihydro-5h-dibenzo-c,e azepin-5-ones and methods for preparing them - Google Patents

Abstract

1393600 Dibenzo - [c,e] - azepine - 5 - ones MERCK & CO Inc 3 Aug 1972 [9 Aug 1971] 36338/72 Heading C2C Novel compounds I in which each of R 1 , R 2 , R 9 and R 10 is a hydrogen or halogen atom or an alkoxy, cyano, hydroxy, nitro, amino, dialkylamino, dialkenylamino, alkylamino, arylamino, substituted arylamino, aralkylamino, substituted aralkylamino, alkenylamino, alkanoylamino, aroylamino, substituted aroylamino, alkanoyl, aroyl, substituted aroyl, mercapto, alkylthio, arylthio, aralkylthio, substituted aralkylthio, alkenylthio, alkylsulfinyl, alkenylsulfinyl, arylsulfinyl, substituted arylsulfinyl, aralkylsulfinyl, substituted aralkylsulfinyl, alkylsulfonyl, alkenylsulfonyl, arylsulfonyl, substituted arylsulfonyl, aralkylsulfonyl, substituted aralkylsulfonyl, carbamoyl, monoalkylcarbamoyl, dialkylcarbamoyl, arylcarbamoyl, substituted arylcarbamoyl, aralkylcarbamoyl, substituted aralkylcarbamoyl, monoalkenylcarbamoyl, dialkenylcarbamoyl, amidino, ureido, carbamoyloxy, N-alkylcarbamoyloxy, N,N-dialkylcarbamoyloxy, haloalkyl, sulfamoyl, alkylsulfamoyl, dialkylsulfamoyl, haloalkoxy, haloalkylthio, alkenyloxy, aryloxy, substituted aryloxy, aralkyloxy, substituted aralkyloxy, carboxyalkyl, or carboxyalkenyl radical, where the term "substituted" means "having a methoxy, methylthio, halogen or amino substituent in the aryl residue"; R 3 is a hydrogen atom or an alkyl, alkanoyl, aroyl, alkoxyalkyl, aminoalkyl, carboxyalkyl, hydroxyalkyl, alkenyl, alkoxycarbonyl, carbamoyl, carboxyalkoxy, mercaptoalkyl, alkylthioalkyl, aralkylthioalkyl, alkylsulfinylalkyl or aralkylsulfinylalkyl radical; and R 4 is a hydrogen atom or an acylimido or acetamido radical, with the provisos that when R 3 is hydrogen or alkyl at least one or R 1 , R 2 and R 4 is other than hydrogen, that if R 1 is hydrogen, so is R 9 , and that if R 2 is hydrogen, so is R 10 , are prepared from 6,7- dihydro - 5H - dibenzo - [c,e] - azepin - 5 - one (A). Compounds in which R 3 is H are prepared by nitrating in the presence of an acid, compound (A) to form a 9-nitro or 3-, 9-dinitro derivative (B) which is reduced by catalytic hydrogenation to the mono or diamino-6,7- dihydro-5H-dibenzo-[c,e]-azepin-5-one (C). This amino derivative is diazotized to the corresponding mono or di-halo derivative which is treated with cuprous cyanide to form mono- or di-cyano-azepin-5-one (E). Hydrolysis of this compound yields mono- or di-carbamoyl-azepine- 5-one and the corresponding acid. Reaction of mono- or di-carboxy-azepine-5-one with a trihaloforming agent yields the mono- or di-trihalomethyl derivative and its reaction with acid halide forming reagent followed by amination gives mono- or di-substituted carbamoyl derivatives. (E) is treated with an alkoxyamidino forming reagent to give mono- or di-(alkoxyamidino)-azepine-5-one which is converted to mono- or di-(amidino) dibenzo-[c,e]-azepin-5-one. N-substituted azepin-5-ones are obtained from (A) or (B) by reaction with an R 3 forming agent. Mono- or di-amino-N-(R 3 )-azepin-5-one is diazotized in the presence of an acid to give mono- or di-hydroxy-N-(R 3 )-azepin-5-one (B) which with an alkyl or aralkyl halide forms the mono- or di- (alkoxy or aralkoxy) derivative which may be further nitrated in the 10-position. From (B<SP>1</SP>) are also produced mono- or di-alkyl carbamoylazepine-5-one, and mono- or di(haloalkoxy)- azepin-5-one. Mono- or di-amino-N-(R 3 )-azepin- 5-one (Y) is diazotized and treated with a xanthate to form mono- or di-mercapto-azepine- 5-one which forms mono or di-(haloethylthio) derivative. From Y is produced mono- or di- (ureido)-azepin-5-one. Mono or di-sulphur derivatives are obtained from mono- or di-halo-N- (R 3 )-azepine-5-one which is treated with a dialkyl-aryl- or aralkyl disulphide to form a sulphide derivative which may be oxidized to the sulphoxide and sulphone. (A) is treated with an alkoxycarbonyl forming reagent to yield 6- alkoxycarbonyl-azepine-5-one which is converted to the 6-aminocarbonyl derivative. Reaction of compound (C) with an acyl forming reagent yields the mono- or di-acyl N-(acyl)-azepin-5-one which may be nitrated in the 10-position. Treatment of (A) with an alkylthioalkyl halide yields N-(alkylthioalkyl)-azepine-5-one which may be oxidized to the sulphinyl derivative. Reaction of N-(R 3 )-dibenz-[c,e]-azepin-5-one with a halo sulphonic acid and an amine base yields mono- or di-sulphonyl-azepin-5-ones. Other R 4 7-(R 4 )-dibenz-[c,e]-azepin-5-ones are prepared from (A) or from the nitro derivative by reaction with N-halo-imide (R 4 being either phthalimido or succinimido). Compounds I are anti-inflammatory, antipyretic and analgesic agents which with a carrier form a pharmaceutical preparation which may be administered orally, parenterally or topically.