FUSED-RING BENZOTHIADIAZEPINE AND BENZO-THIADIAZOCINE DERI VATIVES

摘要

1476684 Pyrimidino - benzothiadiazepines and -benzothiadiazocines and intermediates therefor E R SQUIBB & SONS Inc 3 July 1974 [26 July 1973] 29521/74 Heading C2C Novel pyrimidino benzothiadiazepines and pyrimidino benzothiadiazocines of the Formula I wherein m is 1 or 2, n is 0 or 1, Z is -S- or -SO 2 -, RSP11/SP is a hydrogen atom or a C 1-4 alkyl group, R is a hydrogen, fluorine, chlorine or bromine atom or a C 1-4 alkyl, benzyl, phenyl or monosubstituted phenyl group, the substituent being fluorine, chlorine, bromine, iodine, C 1-4 alkyl, C 1-4 alkoxy or CF 3 , and RSP1/SP is a hydrogen, fluorine, chlorine or bromine atom or a trifluoromethyl, C 1-4 alkyl or di-(C 1-4 alkyl) sulphamoyl group, and salts thereof, provided that when m is 1, R occupies position -4 or -5 of the pyrimidine ring, but when R is halogen it occupies only position-5, and when m is 2 the two Rs occupy the 4- and 5-positions but only one of them can be halogen and it must occupy the 5-position, are obtained by cyclizing compounds of the Formula IV or V in which X is a chlorine or bromine atom. Compounds of the Formula IV above may be obtained by reacting appropriate 2-aminopyrimidines with haloalkyl o-bromo phenyl thioethers of the Formula III Compounds of the Formula V above may be obtained by reacting compounds of the Formula IV with water-miscible alcohols and alkali metal C 1-3 alkoxides. Haloalkyl o-bromophenyl thioethers of the Formula III above in which Z is a sulphur atom, may be obtained by reacting the corresponding o-bromophenyl thiols (obtainable from the corresponding o-bromo anilines) with haloalkane sulphonic acid, sodium salts and halogenating the o-bromophenylthio alkane sulphonic acid sodium salts so produced, or by reacting the o-bromophenyl thiols with dihaloalkanes. 3 - Bromo - 4 - aminobenzotrifluoride may be obtained by brominating p-aminobenzotrifluoride. 2 - Bromo - α,α,α - trifluoro - m - tolyl bromomethyl sulphone may be obtained by acetylating α,α,α - trifluoro m - toluidine to give α,α,α- trifluoroacetotoluidide, further acetylating this to α,α,α - trifluoro - m - N,N - diacetotoluidide, brominating this to 2-bromo-α,α,α-m-N,N-diacetotoluidide, hydrolysing this with hydrochloric acid to give 2-bromo-α,α,α-trifluoro-mtoluidine hydrochloride, converting this via 2- bromo-α,α,α-trifluoro-m-toluene sulphonyl chloride to sodium 2 - bromo - α,α,α - trifluoro - mtoluene sulphonate and reacting this with dibromomethane. Pharmaceutical compositions contain compounds of Formula I as active ingredients.