发明名称 |
Process for the preparation of valsartan |
摘要 |
The present invention relates to a process for the preparation of pure Valsartan (I) substantially free from impurities of formulae (Ia), (Ib), and (Ic), which comprises: (i) condensing 2-(4′-bromomethylphenyl)benzonitrile of formula (II) with L-valine methyl ester hydrochloride of formula (V) in the presence of a base in a solvent to produce N-[(2′-cyanobiphenyl-4-yl)methyl]-(L)-valine methyl ester of formula (VI); (ii) treating the compound VI of step (i) with acid followed by treating with base to produce pure compound VI substantially free from dimeric impurity of formula (Via); (iii) reacting the pure compound of formula (VI) with n-valeryl chloride in the presence of a base to produce pure N-valeryl-N-[(2′-cyanobiphenyl-4-yl)methyl]-(L)-valine methyl ester (VII) substantially free from alkene impurity of formula (Vila); (iv) reacting the compound of formula (VII) with trialkyltin chloride and a metal azide in a solvent at a reflux temperature to produce N-(1-oxopentyl)-N-[[2′-(2-tributyltintetrazol-5-yl)-(1,1′-biphenyl)-4-yl]methyl]-(L)-valine methyl ester of formula (VHIb) free from thermal degradation impurity (Villa); (v) hydrolyzing the compound of formula (VHIb) in the presence of alkaline conditions to produce Valsartan (I). |
申请公布号 |
US8981109(B2) |
申请公布日期 |
2015.03.17 |
申请号 |
US201113261552 |
申请日期 |
2011.06.24 |
申请人 |
Aurobindo Pharma Ltd |
发明人 |
Chinta Raveendra Reddy;Nangi Gangadhara Bhima Shankar;Nayini Mahendar Reddy;Yallapa Somappa Somannavar;Budidet Shankar Reddy;Aminul Islam;Meenakshisunderam Sivakumaran |
分类号 |
C07D257/04 |
主分类号 |
C07D257/04 |
代理机构 |
|
代理人 |
Akhave Jay R |
主权项 |
1. A process for the preparation of Valsartan of formula (I) substantially free from impurities of formulae (Ia), (Ib), and (Ic),which comprises:
(i) condensing 2-(4′-bromomethylphenyl)benzonitrile of formula (II), with L-valine methyl ester hydrochloride of formula (V), in the presence of a base in a solvent to produce N-[(2′-cyanobiphenyl-4-yl)methyl]-(L)-valine methyl ester of formula (VI); (ii) treating the compound (VI) of step (i) with acid followed by treating with base to produce pure compound (VI) substantially free from dimeric impurity of formula (VIa); (iii) reacting the pure compound of formula (VI) with n-valeryl chloride in the presence of a base to produce pure N-valeryl-N-[(2′-cyanobiphenyl-4-yl)methyl]-(L)-valine methyl ester (VII) substantially free from alkene impurity of formula (VIIa); (iv) reacting the compound of formula (VII) with trialkyltin chloride and a metal azide in a solvent at a reflux temperature to produce N-(1-oxopentyl)-N-[[2′-(2-tributyltintetrazol-5-yl)-(1,1′-biphenyl)-4-yl]methyl]-(L)-valine methyl ester of formula (VIIIb) free from thermal degradation impurity (VIIIa); (v) hydrolyzing the compound of formula (VIIIb) in the presence of alkaline conditions to produce Valsartan (I). |
地址 |
Hyderabad IN |