GB1034933A — 4-demethylamino-4-substituted amino 6-demethyl tetracyclines

USPTO Abstract

The invention relates to broad-spectrum tetracycline derivatives of formula <FORM:1034933/C2/1> where R is hydrogen or halogen; R1 is hydrogen or C1- 6 alkyl; R2 is C1- 6 alkyl or hydroxy C1- 6 alkyl, with the proviso that R1 and R2 cannot both be methyl. Specified are 4-dedimethyl-amino - 4 - methylamino - 6 - demethyltetracyline and -chlortetracycline; 4-dedimethylamino - 4 - ethylamino - 6 - demethyltetracycline and -bromotetracycline; 4 - dedimethylamino - 4 - methylethylamino - 6-demethyl-tetracycline and -7-iodo-tetracycline; 4 - n - propylamino-, 4 - n - butylamino-, 4 -(beta hydroxyethyl)-, 4-(3-hydroxypropy)-, 4 - methyl - n - propylamino-, 4 - diethylamino and 4 - methyl - (beta hydroxyethyl)amino-derivatives of 4-dedimethylamino-6-demethyl tetracycline. The 4-mono substituted amino compounds of formula <FORM:1034933/C2/2> where R is hydrogen or halogen and R2 is C1- 6 alkyl or hydroxy C1- 6 alkyl, are prepared by reductively aminating a 4-hydroxy-tetracyl-oxide of formula <FORM:1034933/C2/3> where R is as defined above, with a C1- 6 alkylamine or hydroxy C1- 6 alkylamine at 0 DEG to 50 DEG C. and 1 to 4 atmospheres. Compounds of Formula I are produced by alkylating the corresponding tetracycline of Formula I in which at least R1 or R2 is hydrogen by means of (a) an alkyl halide, alkyl sulphonate or alkyl sulphate or (b) an alkanal (i.e. aldehyde) in a reducing medium at 0 DEG C. to 50 DEG C. Hydrogen and a catalyst, zinc, tin or iron in hydrochloric acid, aluminium amalgam or formic acid are suitable reducing agents.