Title:
METHOD FOR SYNTHESIZING VALSARTAN
Document Type and Number:
WIPO Patent Application WO/2020/010643
Kind Code:
A1
Abstract:
A method for synthesizing valsartan, comprising the steps of: synthesizing a valsartan methyl ester intermediate to obtain a reaction mixture of the valsartan methyl ester intermediate; diluting the reaction mixture by salt water or water, and then using a first extraction solvent to extract the valsartan methyl ester intermediate; adding alkali to an organic layer containing the valsartan methyl ester intermediate for hydrolyzing, removing the organic layer, regulating pH of a water layer to be acidic by using acid, using the first extraction solvent to extract, concentrating a part of solvent, or distilling the solvent to dryness, and then adding a new solvent; finally, crystalizing, filtering, and drying to obtain the valsartan. The synthesization method provided in the present invention can avoid from the process source the possibility that highly toxic impurities such as N-nitrosodimethylamine (NDMA), a valsartan impurity K, and valsartan N-chloride generated in the azide quenching process are introduced into the valsartan methyl ester intermediate, and are further introduced into the valsartan active ingredient, thereby ensuring the valsartan medication safety.
Inventors:
ZHOU XIAOHUI (CN)
ZHU XIAOREN (CN)
ZHU YUANXUN (CN)
DONG PENG (CN)
WANG PENG (CN)
LIN JINSHENG (CN)
ZHU WENQUAN (CN)
LI MIN (CN)
ZHU XIAOREN (CN)
ZHU YUANXUN (CN)
DONG PENG (CN)
WANG PENG (CN)
LIN JINSHENG (CN)
ZHU WENQUAN (CN)
LI MIN (CN)
Application Number:
PCT/CN2018/096006
Publication Date:
January 16, 2020
Filing Date:
July 17, 2018
Export Citation:
Assignee:
ZHEJIANG HUAHAI PHARM CO LTD (CN)
ZHEJIANG HUAHAI TIANCHENG PHARMACEUTICAL CO LTD (CN)
ZHEJIANG HUAHAI ZHICHENG PHARMACEUTICAL CO LTD (CN)
ZHEJIANG HUAHAI TIANCHENG PHARMACEUTICAL CO LTD (CN)
ZHEJIANG HUAHAI ZHICHENG PHARMACEUTICAL CO LTD (CN)
International Classes:
C07D257/04; C07B63/00
Foreign References:
| CN101253131A | 2008-08-27 | |||
| CN102911128A | 2013-02-06 | |||
| CN102863398A | 2013-01-09 | |||
| CN103012300A | 2013-04-03 | |||
| CN102010381A | 2011-04-13 | |||
| CN104045602A | 2014-09-17 | |||
| CN201810771261A | 2018-07-13 | |||
| CN103613558A | 2014-03-05 |
Other References:
XU MENG: "Research on the Synthesis of High Optical Purity Valsartan", CHINESE MASTER'S THESES FULL-TEXT DATABASE, 1 April 2011 (2011-04-01), pages 1 - 81, XP055773063
See also references of EP 3822259A4
See also references of EP 3822259A4
Attorney, Agent or Firm:
PATENTSINO IP FIRM (CN)
Download PDF: