Description
3-amino-6-methoxypyridazine: a critical pharmaceutical intermediate.
It can be used for pyridopyrimidine compounds with remarkable biological activity or medicines, such as the anticancer drug Ruugeli, which can be used for treating indications such as pain caused by endometriosis, uterine fibroids and advanced prostate cancer. At present, many reports on the preparation method of the compound exist, and various process impurities such as 3-amino-6-chloropyridazine, 3-amino-6-hydroxypyridazine, 3-chloro-6-hydroxypyridazine, 3-dichloropyridazine, 3, 6-dimethoxypyridazine, 3-amino-6-methoxypyridazine, 3-aminopyridazine and the like are often introduced in the process of the conventional synthesis process.
Synthesis
A total of 3.40 g. (0.026 mol) 3-amino-6-chloropyridazine was placed in a Carius tube with a solution of sodium methoxide in methanol [prepared from 0.61 g. (0.027 mol) of clean sodium metal and 50 ml. of methanol], and the Carius tube was sealed. The tube was placed in a Carius furnace for 20 hours. After the tube was cooled and opened, the contents were removed, and the light brown solid was filtered off. The filtrate was evaporated to dryness at room temperature under an air jet. The resulting orange-brown crystalline solid was dissolved in a 60:40 petroleum ether-chloroform solution, treated with activated charcoal and filtered. There was obtained, upon. Talline solid fromn-amyl chloride accompanied by treat- 3 ment with activated charcoal yielded 0.51 g. of a white, crystalline solid 3-amino-6-methoxypyridazine melting at 103-105 ℃.
