Method of preparation of crystal forms of 4-(cyclopropylmethoxy)-n-(3,5-dichloro-1-oxidopyridyn-4-yl)-5-methoxypyridine-2-carboxamide and crystal forms thereof

Patent metadata

Field	Value
Publication number	US-9533953-B2
Application number	US-201314647799-A
Country	US
Kind code	B2
Filing date	Nov 28, 2013
Priority date	Nov 28, 2012
Publication date	Jan 3, 2017
Grant date	Jan 3, 2017

Abstract

The present invention relates to a process of preparation of Crystal Forms of 4-(cyclopropylmethoxy)-N-(3,5-dichloro-1-oxidopyridin-4-yl)-5-methoxypyridine-2-carboxamide of formula (I), said Crystal Forms which are designated as Crystal Forms A to I A and their use as a medicament.

First claim

The invention claimed is:

1. A process for the preparation of Crystal Form A of 4-(cyclopropylmethoxy)-N-(3,5-dichloro-1-oxidopyridin-4-yl)-5-methoxypyridine-2-carboxamide of formula (I)

having an X-ray (λCu) powder diffraction pattern with main peaks at about 9.5, 10.9, 11.7, 13.3, 13.9, 14.9, 16.1, 17.6, 18.6, 19.2±0.2 degrees 2-theta, the process comprising heating 4-(cyclopropylmethoxy)-N-(3,5-dichloro-1-oxidopyridin-4-yl)-5-methoxypyridine-2-carboxamide in a solvent selected from the group consisting of propanol, isopropanol, toluene, ethyl acetate, a mixture of tetrahydrofuran and water, and a mixture of ethanol and water to provide a solution, and cooling the solution to induce crystallization.

2. The process according to claim 1 wherein the process further comprises filtration and drying.

3. A crystal form of 4-(cyclopropylmethoxy)-N-(3,5-dichloro-1-oxidopyridin-4-yl)-5-methoxypyridine-2-carboxamide of formula (I):

which is
crystal Form A, having an X-ray (λCu) powder diffraction pattern with main peaks at about 9.5, 10.9, 11.7, 13.3, 13.9, 14.9, 16.1, 17.6, 18.6, 19.2±0.2 degrees 2-theta.

4. A pharmaceutical composition comprising the crystal form of 4-(cyclopropylmethoxy)-N-(3,5-dichloro-1-oxidopyridin-4-yl)-5-methoxypyridine-2-carboxamide of formula (I) according to claim 3 , and at least one pharmaceutically acceptable excipient.

5. A method of treating Alzheimer's disease or Parkinson's disease in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the crystal form of 4-(cyclopropylmethoxy)-N-(3,5-dichloro-1-oxidopyridin-4-yl)-5-methoxypyridine-2-carboxamide of formula (I) according to claim 3 .

Assignees

• Sanofi Sa

Inventors

• Billot Pascal
• Brige Didier
• Giuliani Alexandre
• Elmaleh Hagit
• Perrin Marc-Antoine

Classifications

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title

• C07D213/89 Primary

  with hetero atoms directly attached to the ring nitrogen atom · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title