PROCESS FOR THE PREPARATION OF 2,4-DIAMINO-5-(3',4', 5'-TRIMETHOXYBENZYL)PYRIMIDINE

摘要

The invention relates to a novel process for the preparation of 2,4-diamino-5-/3',4',5'-trimethoxybenzyl/-pyrimidine of the formula I /I/ through the reaction of an alpha-/3 ,4 ,5 -trimethoxybenzyl/- -beta-/substituted/-acrylonitrile with guanidine. According to the invention an alpha-/3 ,4 ,5 -trimethoxy-benzal/-beta-methoxypropionitrile of the formula III /III/ is reacted with a diethylene glycol monoalkyl ether of the formula IV, HO-CH2CH2-O-CH2CH2-OR /IV/ wherein R is an alkyl group having 1 to 4 carbon atoms, at 60 to 90 .degree.C in the presence of an alkali metal alkoxide, and the obtained benzyl isomer of the formula II, /II/ wherein R is as stated above, is reacted - optionally without separation - with guanidine in the presence of an alkanol having 4 to 8 carbon atoms. The process of the invention allows the economical production of trimethoprim having very high antibacterial activity. The total yield calculated for 3,4,5-trimethoxy-benzaldehyde being about 80 per cent is not detrimentally influenced by the enhancement of the batch size. Trimethoprim of very high purity is produced from the compound of the formula III in a single step.