Amorphous Trisodium Sacubitril Valsartan and process for its preparation

Patent metadata

Field	Value
Publication number	US-10995060-B2
Application number	US-201716345576-A
Country	US
Kind code	B2
Filing date	Oct 28, 2017
Priority date	Oct 28, 2016
Publication date	May 4, 2021
Grant date	May 4, 2021

Abstract

The present invention provides for crystalline Form B1 of N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenyl-methyl)-4-amino-2R-methyl butanoic acid ethyl ester sodium salt, crystalline Form B2 of N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-2R-methyl butanoic acid ethyl ester sodium salt, a novel process for the preparation of crystalline Form B of N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-2R-methyl butanoic acid ethyl ester sodium salt.

First claim

The invention claimed is:

1. Crystalline form B1 of N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-2R-methyl butanoic acid ethyl ester (sacubitril) sodium salt characterized by an X ray powder diffraction (X RPD) spectrum having peak reflections at about 3.7, 7.4, 11.8, 12.6, 16.4, 16.6, 17.3, 18.4, 19.2, 19.9, 20.7, 22.5 and 23.5±0.2 degrees 2 theta, as shown in FIG. 1 .

2. Crystalline form B2 of N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-2R-methyl butanoic acid ethyl ester (sacubitril) sodium salt characterized by an X-ray powder diffraction (X RPD) spectrum having peak reflections at about 3.2, 3.6, 4.0, 6.4, 12.1, 17.8, 18.5, 20.0, 21.0 and 21.7±0.2 degrees 2 theta, as shown in FIG. 2 .

3. A process for the preparation of crystalline form B1 of claim 1 , N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-2R-methyl butanoic acid ethyl ester (sacubitril) sodium salt, the process comprising:
a) heating a solution of sacubitril sodium salt in methyl isobutyl ketone at elevated temperature;
b) cooling the solution from step a); and
c) isolating the crystalline form B1 of N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-2R-methyl (sacubitril) sodium salt.

4. A process for the preparation of crystalline form B2 of claim 2 , N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-2R-methyl butanoic acid ethyl ester (sacubitril) sodium salt, the process comprising:
a) converting sacubitril calcium salt into sacubitril free acid in presence of HCl and in ethyl acetate solvent at elevated temperature;
b) treating sacubitril from step a) with sodium hydroxide and
c) isolating the crystalline form B2 of N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-2R-methyl butanoic acid ethyl ester (sacubitril) sodium salt.

Assignees

• Biocon Ltd

Inventors

• Charyulu Palle Venkata Raghavendra
• Patel Pratik Rameshchandra
• Venu Thirunelimada Devaiah
• Vidyasagar Reddy Avathu
• Shanmughasamy Rajmahendra

Classifications

• C07D257/04 Primary

  Five-membered rings · CPC title

• C07C233/51

  having the carbon atom of the carboxamide group bound to an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P9/04

  Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure · CPC title

• A61K2300/00

  Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 · CPC title