Sodium Methoxide → 2,4-Pyrimidinediamine, 5-(3-((4'-chloro(1,1'-biphenyl)-4-yl)oxy)propoxy)-6-methyl-, monohydrochloride

Participants

Reaction Conditions

Reaction Steps

2,4-Diamino-5-hydroxy-6-methylpyrimidine dihydrogen sulphate (137.5 g) was added to a stirred solution of sodium methoxide [prepared by dissolving sodium (39.8 g) in anhydrous methanol (2350 ml)]. The stirred mixture was heated at reflux for 30 minutes and then for a further 150 minutes during the gradual addition of a solution of 3-[4-(4-chlorophenyl)-phenoxy]propyl bromide (188 g) in anhydrous tetrahydrofuran (940 ml) and then the mixture was stirred and heated at reflux for a further 18 hours. Part of the solvent (approximately 2400 ml) was removed by distillation at atmospheric pressure and the remaining mixture was diluted with water (3000 ml). The resulting suspension was cooled to 40° C., and the solid was filtered off, washed well with water and dried at 85° C. The solid was then dissolved in hot dimethylformamide (1000 ml) and the resulting solution was filtered through diatomaceous earth and treated, successively, with concentrated hydrochloric acid (50 ml) and acetone (2000 ml). The resulting suspension was cooled to 10° C. and filtered, and the solid was washed well with acetone to give 2,4-diamino-5-[3-{4-(4-chlorophenyl)phenoxy}propoxy]-6-methylpyrimidine monohydrochloride (178 g), m.p. 263°-265° C. (with slight decomposition).

Provenance & Evidence