Novel quinazoline compounds and production thereof

摘要

Novel quinazolines of the formula (wherein either (a) A is NH2 and X is chlorine or methyl, or (b) A is Ar-CH(R1)-N(R2)- and X is H, chlorine or methyl, R1 and R2 being H or C1- 4 alkyl, at least one of X, R1 and R2 being other than H, and Ar being phenyl which may be mono-, di- or tri-(C1- 4 alkyl), mono- or di-halo, hydroxy, mono-, di- or tri-(C1- 4 alkoxy), carboxy, carb-(C1- 4 alkoxy), nitro, amino, mono- or di-(C1- 4 alkyl)amino or acetamido substituted, naphthyl which may be halo, nitro, hydroxy, amino or C1- 4 alkoxy substituted, furyl, thienyl, or pyridyl) and acid-addition salts thereof, are prepared (1) for compounds (a), by reducing the corresponding 6-nitro compounds; (2) for compounds (b), wherein R2 is H, by reacting the corresponding 6-amino-compounds with the appropriate aldehyde Ar-CHO or ketal Ar-C(alkyl)=(O-alkyl)2 and reducing the resulting imine; or (3), for compounds (b) wherein R2 is alkyl, by reacting a 2-amino-5-(Ar-CH.R1-N.R2)-6-X-benzonitrile with cyanamide or dicyandiamide. Specification 1,045,180 is referred to as disclosing starting materials and intermediates for process (2). 2,4 - Diamino - 5 - chloro - 6 - nitro - quinazoline is prepared by reacting 6-chloro-anthranilonitrile with cyanamide dihydrochloride to give 2,4 - diamino - 5 - chloro - quinazoline hydrochloride, and nitrating the free base. 2,4-Diamino - 5 - methyl - 6 - nitro - quinazoline is prepared by nitrating 6-chloro-o-tolunitrile to give 6 - chloro - 3 - nitro - o - tolunitrile and reacting this with guanidine carbonate, the product being isolated as the acetate salt. 2,4,6 - Triamino - quinazoline is prepared by nitrating 2,4-diamino-quinazoline to give 2,4-diamino - 6 - nitro - quinazoline and reducing this. 2 - Amino - 5 - [(N - benzyl - N - methyl)amino]-benzonitrile is prepared by reacting 5-chloro-2-nitro-benzonitrile with N-methylbenzylamine to give 5 - [(N - benzyl - N - methyl) - amino] - 2 - nitro-benzonitrile and reducing this. The quinazolines of the invention, which are stated to possess antibacterial, antiparasitic, anthelmintic and diuretic activity may be made up into pharmaceutical compositions for oral or parenteral administration with suitable carriers.