Diuretic 3-sulphamoyl 5-alkylamino benzoic acids - from N-protected 4-halo 3-sulphamoyl benzoic acids

摘要

Sulphamoyllbenzoic acids of formula (I): (where A is 1-4C alkyl (opt. interrupted by O,N or S and opt. substd. by halogen, OH, SH, CN or NH2), a 3-5C carbocyclic ring, furyl or thienyl gp. or a phenyl or benzyl gp. (opt. ring substd., X is OR2, SR2, SOR2, SO2R2 or NR3R4, R2 is 1-5C alkyl, 3-6C acycloalkyl, 1-3C alkyl substd. by phenyl, pyridyl gp. opt. substd. by 1-3C alkyl, halogen, alkoxy, OH,NH2 or mono- or disbustd. amino; R3 and R4 are 1-3C alkyl (opt. joined to form a ring) or R3 can be phenyl, or NR3R4 is 1-piperazinyl, R is H, 1-6C alkyl or 3-6C cycloalkyl) are prepd. by (a) nitrating an N-protected sulphamoylbenzoic acid of formula (II) (b) opt. esterifying the product (III) (when R=H), (c) reacting the product with HX to (IV) (d) reducing the NO2 gp. to NH2 to give (V) (e) acylating the NH2 gp. with A-CO-L giving (VI) (where L is a leaving gp.), (f) reducing the A-CO gp. to A-CH2 with a borane or complex borohydride in the presence of a Lewis acid giving (VII) (g) hydrolysing off the protecting gp., and opt. (h) esterifying the prod. (where Y is halogen; B is =CR5-NR6R7; R5 is H or lower alkyl and R6 and R7 are lower alkyl or two of R5-7 can be joined to form a ring; R1 is 1-6C alkyl or 3-6C cycloalkyl) of the intermediates (VI) and (VII) are new cpds. Cpds. (I) are diuretics and saluretics. Introduction of the protecting gp. allows (II) to be nitrated under mild conditions without the other functional gps. being affected.