Process

Patent metadata

Field	Value
Publication number	US-9603816-B2
Application number	US-201314132221-A
Country	US
Kind code	B2
Filing date	Dec 18, 2013
Priority date	Dec 16, 2010
Publication date	Mar 28, 2017
Grant date	Mar 28, 2017

Abstract

The present invention relates to a process for the preparation of S-[2-[1-(2 -ethylbutyl)cyclohexylcarbonylamino]-phenyl] 2-methylthiopropionate which is useful as a pharmaceutically active compound.

First claim

The invention claimed is:

1. A process for the preparation of a compound of formula (Ia):

wherein R 1 is a (C 1 -C 8 ) aryl, Which comprises reacting a compound of formula (II′):

wherein R is H or a compound of the formula:

with H 2 in the presence of (1) an acylating agent anhydride derivative [((C 1 -C 8 )alkyl)C(═O)] 2 or [aryl(C═O)] 2 O or a halide derivative ((C 1 -C 8 )alkyl)C(═O)halide or aryl(C═O) halide and (2) a heterogeneous transition metal hydrogenation catalyst.

2. A process for the preparation of a compound of formula (Ia) and Formula (X):

wherein R 1 is a (C 1 -C 8 ) aryl, Which comprises reacting a compound of formula (II′):

wherein R is H or a compound of the formula:

with H 2 in the presence of (1) an acylating agent anhydride derivative [((C 1 -C 8 )alkyl)C(═O)] 2 or [aryl(C═O)] 2 O or a halide derivative ((C 1 -C 8 )alkyl)C(═O)halide or aryl(C═O)halide and (2) a heterogeneous transition metal hydrogenation catalyst.

3. The process according to claim 2 , wherein R is:

4. The process according to claim 1 wherein R 1 is isopropyl and the acylating agent is isobutyric anhydride or isobutyryl halide.

5. The process according to claim 1 wherein the acylating agent is isobutyric anhydride.

6. The process according to claim 5 , wherein 2.0 to 4.0 equivalents of is obutyric anhydride with respect to the disulfide of formula (II′) is used.

7. The process according to claim 1 , wherein said process is performed in the presence of a solvent or a mixture of two or more solvents.

8. The process according to claim 7 , wherein the solvent is an organic solvent.

9. The process according to claim 7 , wherein the solvent is an ether like solvent, ester like solvent, aliphatic hydrocarbon solvent, saturated alicyclic hydrocarbon solvent, aromatic solvent or a mixture thereof.

10. The process according to claim 7 , wherein the solvent is an aliphatic hydrocarbon solvent, saturated alicyclic hydrocarbon solvent, or aromatic solvent.

11. ihe process according to claim 1 , wherein the acylatmg agent is an anhydride derivative which can act as a solvent or co-solvent with a molar ratio anhydride/amidodisulfide of 2 to 19.

12. The process according to claim 1 , wherein the H 2 is added at a pressure of at least 0.1 bar.

13. The process according to cliam 1 , wherein the reaction is carried out at temperature up to 150° C.

14. The process according to claim 1 , wherein the heterogeneous transition metal hydrogenation catalyst is a Raney catalyst, Pd/C, Pd(OH) 2 /C, Nanoparticulate Palladium(0) microencapsulated in polyurea matrix, Au/TiO 2 , Rh/C, Ru/Al 2 O 3 , Ir/CaCo 3 , Pt/C, or a mixture thereof.

15. The process according to claim 1 , wherein the heterogeneous transition metal hydrogenation catalyst is a Raney catalyst, Pd/C, Pd(OH) 2 /C, Au/TiO 2 , Rh/C, Ru/Al 2 O 3 , Ir/CaCO 3 , Pt/C, or a mixture thereof.

16. The process according to claim 1 , wherein the heterogeneous transition metal hydrogenation catalyst is Pd/C, Pd(OH) 2 /C, Au/TiO 2 , Rh/C, Ra—Ni or Pt/C.

17. The process according to claim 1 , wherein the heterogeneous transition metal hydrogenation catalyst is Pd/C or Ra—Ni.

Assignees

• Hoffmann La Roche

Inventors

• Mair Hans-Juergen
• Reents Reinhard
• Scalone Michelangelo
• Wang Shaoning
• Zogg Andreas

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• C07C319/06 Primary

  from sulfides, hydropolysulfides or polysulfides · CPC title

• C07D277/64

  with only hydrocarbon or substituted hydrocarbon radicals attached in position 2 · CPC title

• A61K31/16 Primary

  Amides, e.g. hydroxamic acids · CPC title