PROCESS FOR PREPARING VALSARTAN
0 Assignments
0 Petitions
Accused Products
Abstract
The invention relates to novel compound of formula (IV), which is an organic acid salt of N-[(2′-cyanobipheny1-4-yl)methyl]-(L)-valine ester. This compound is an useful intermediate for process of preparation of Valsartan of formula (I), chemically known as (S)-N-(1-Carboxy-2-methylprop-1-yl)-N-pentanoyl-N-[2′-(1H-terazol-5-yl)biphenyl-4-ylmethyl]amine. This invention also relates to a process for preparing Valsartan using novel intermediate of formula (IV).
3 Citations
30 Claims
-
1-14. -14. (canceled)
-
15. A process for the preparation of (S)-N-(1-Carboxy-2-methylprop-1-yl)-N-pentanoyl-N-[2′
- -(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]amine (Valsartan) of formula I comprising;
(a) reacting 4-halomethyl-2′
-cyanobiphenyl of formula (II)wherein X represents halogen selected from Cl or Br, with L-valine ester derivative of formula (III) wherein R1 represents C1-C4 alkyl selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, 2-methylpropyl or benzyl;
in presence of base and solvent, optionally in presence of catalyst;
to form N-[(2′
-cyanobiphenyl-4-yl)methyl]-(L)-valine ester derivative of formula (IVa).wherein R1 represents C1-C4 alkyl selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, 2-methylpropyl or benzyl (b) treating N-[(2′
-cyanobiphenyl-4-yl)methyl]-(L)-valine ester derivative of formula (IVa) with organic acid to obtain compound of formula (IV).wherein R1 represents C1-C4 alkyl selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, 2-methylpropyl or benzyl;
S represents organic acid selected from oxalic acid, acetic acid, formic acid, malic acid, maleic acid, malonic acid, succinic acid, furmaric acid, phthalic acid, terephthalic acid, citric acid, tartaric acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, trifluoroacetic acid, ascorbic acid and the like.(c) Acylating the compound of formula (IV) with Valeroyl halide of formula (V) wherein X is halogen selected from Cl or Br;
in the presence of base and water, optionally in organic solvent;
to obtain compound of formula (VI)wherein R1 represents C1-C4 alkyl selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, 2-methylpropyl or benzyl (d) converting the compound of formula (VI) to obtain compound formula (I) by the method such as here in described or by the conventional method. - View Dependent Claims (16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29)
- -(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]amine (Valsartan) of formula I comprising;
-
30-32. -32. (canceled)
Specification