| Abstract: | Brodimoprim (1) is a new antibacterial benzylpyrimidine with a broad spectrum of antimicrobial activities. An improved synthetic method of (1) was reported in this paper from 4-bromo-3,5-dimethoxybenzaldehyde (2) through Knoevenagel condensation, 1,3-prototropic isomerization and cyclization with overall yield of 53.8% which was 40.2% in the early report. As a key intermediate, cinnamonitrile (3) was prepared by the condensation of 2 with 3- methoxypropan-enitrile, which was generated in situ from acrylonitrile with methanolic sodium methoxide. It was found that 3 could be converted easily into the corresponding benzyl isomer 4 by reacting with ethylene glycol monomethyl-ether. 4 reacted with guanidine to give 1 without isolation and purification. |
