Process for preparation of valsartan intermediate
AssigneeHetero Research Foundation
InventorsBandi Parthasaradhi Reddy, Kura Rathnakar Reddy, Rapolu Raji Reddy, Dasari Muralidhara Reddy, Matta Ramakrishna Reddy
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Abstract
The present invention provides a process for preparation of a key intermediate of valsartan in a pure form and use of this intermediate for the preparation of valsartan or a pharmaceutically acceptable salt in pure form.
Claims14
1) A process for preparing N-[(2-cyano[1,1′-biphenyl]-4-yl)methyl]-L-valine benzyl ester of formula I or an acid addition salt substantially free of N,N-bis-[(2′-cyano[1,1′-biphenyl]-4-yl)methyl]-L-valinebenzylester of formula III
- which process comprises:
- a) preparing a solution of L-valine benzylester in a solvent at about 40-140 deg C. in the presence of a base
- b) adding a solution of 4-Bromomethyl-2-cyanobiphenyl of formula II gradually at least for 1 hour 30 minutes to the solution prepared in step (a) maintaining the temperature at about 40-140 deg C.
- c) maintaining the reaction mass for at least 3 hours at about 40-140 deg C.
- d) isolating the N-[(2′-cyano[1,1′-biphenyl]-4-yl)methyl]-L-valine benzylester of formula I or converting the compound of formula I into an acid addition salt and isolating as the solid.
10) A process for purification of an acid addition salt of N-[(2′-cyano[1,1-biphenyl]-4-yl)methyl]-L-valine benzylester which process comprises stirring the acid addition salt of N-[(2′-cyano[1,1′-biphenyl]-4-yl)methyl]-L-valine benzylester containing impurity of N,N-bis-[(2′-cyano[1,1′-biphenyl]-4-yl)methyl]-L-valinebenzylester or an acid addition salt thereof with ethylacetate and isolating the acid addition salt of N-[(2′-cyano[1,1′-biphenyl]-4-yl)methyl]-L-valine benzylester substantially free of N-bis-[(2′-cyano[1,1′-biphenyl]-4-yl)methyl]-L-valinebenzylester or an acid addition salt thereof.
12) The free base of N-[(2′-cyano[1,1′-biphenyl]-4-yl)methyl]-L-valine benzylester of formula I or a mineral acid addition salt thereof substantially free of N-bis-[(2′-cyano[1,1′-biphenyl]-4-yl)methyl]-L-valinebenzyl ester or an mineral acid addition salt thereof.
Dependencies are inferred from the claim text.