Zeng Yanqun, Cen Guodong, Zhou Guanglin, Zhu Xucheng, Huang Long, Wang Xiaoyu
Chengdu Shibeikang Biomedical Technlogy Co., Ltd., 26-1-2, No.2 Tianyu Road, Chendu Gaoxin West District, Chengdu 611700, China.
Molecules. 2024 Dec 21;29(24):6039. doi: 10.3390/molecules29246039.
A new process route suitable for the industrial production of BAY2433334 has been developed in this paper, which avoids the patent limitations of the originator company of BAY2433334 to the preparation of BAY2433334. BAY2433334 is obtained from (2)-2-aminobutyric acid by esterification, diazotization, condensation reactions, deacetyl deprotection, activation reactions, and Mitsunobu reactions. This method is simple to operate, and the raw materials are inexpensive and readily available. Simultaneously, the product quality is very high; few O-alkylated impurities are generated during the reaction, with a high N-alkylated product/O-alkylated product ratio (above 35-45:1). As a result, the ee value is greater than 99%, which means that there are very few isomers present such that no chiral resolution is required, which greatly reduces the cost.
本文开发了一种适用于BAY2433334工业化生产的新工艺路线，该路线避开了BAY2433334原创公司对BAY2433334制备方法的专利限制。BAY2433334由（2）-2-氨基丁酸经酯化、重氮化、缩合反应、脱乙酰基保护、活化反应和 Mitsunobu 反应制得。该方法操作简便，原料价廉易得。同时，产品质量很高；反应过程中生成的O-烷基化杂质很少，N-烷基化产物/O-烷基化产物比例很高（高于35 - 45:1）。因此，对映体过量值（ee值）大于99%，这意味着几乎不存在异构体，无需进行手性拆分，从而大大降低了成本。
