Browse Prior Art Database

A crystallization process for 4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5- (trifluoromethyl)phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-benzamide Disclosure Number: IPCOM000202210D
Publication Date: 2010-Dec-09
Document File: 2 page(s) / 44K

Publishing Venue

The Prior Art Database

This text was extracted from a PDF file.
This is the abbreviated version, containing approximately 58% of the total text.

Page 01 of 2

 A crystallization process for 4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5- (trifluoromethyl)phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-benzamide

     4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[[4- (3-pyridinyl)-2-pyrimidinyl]amino]-benzamide, reffered to as NLT, of the following formula:



is a tyrosine kinase inhibitor. NLT is administrated as a hydrochloride salt, for the treatment of drug-resistant chronic myelogenous leukemia (CML).

    A crystallization process for purification of NLT is described herein below. The crystallization comprises slurrying NLT in N-methyl pyrrolidone (NMP) and water or in a mixture of NMP and ethanol to obtain a reaction mixture; heating the reaction mixture to form a solution; and cooling the solution. The obtained pure NLT can be converted to NLT HCl, for example, by the process disclosed in WO 2007/014871.

Example 1: Purification of NLT:

    To a 1 liter reactor was added NLT (40 g, 0.151 mol, purity: 99.37% area by HPLC) and N-methyl pyrrolidone (10 volumes, 400 ml) were added. The resulting slurry was heated to 90°C to dissolution. The solution was stirred for 30 minutes, and then filtered through a Hyflow bed. The clear filtrate was returned to the reactor. Soft water (4 volumes, 160 ml) was added, and the reactor was heated up again to 90- 95°C, for 1.5 hour. The solution was then cooled gradually to 25°C during 3 hours. The cooled mixture was then stirred at 25°C for 11 hours. A precipitate...