Browse Prior Art Database

Preparation and impurities of 4-(4-(3-(4-chloro-3-(trifluoromethyl)phenyl)ureido)-3-fluorophenoxy)-Nmethylpyridine- 2-carboxamide Disclosure Number: IPCOM000239367D
Publication Date: 2014-Nov-03
Document File: 2 page(s) / 281K

Publishing Venue

The Prior Art Database

This text was extracted from a PDF file.
This is the abbreviated version, containing approximately 54% of the total text.

Page 01 of 2

Preparation and impurities of 4-(4-(3-(4-chloro-3-(trifluoromethyl)phenyl)ureido)-3-fluorophenoxy)-N- methylpyridine-2-carboxamide


     (referred to as Compound 1) is intermediate in the synthesis of 4-(4-(3-(4-chloro-3- (trifluoromethyl)phenyl)ureido)-3-fluorophenoxy)-N-methylpyridine-2-carboxamide (referred to as Compound

     Disclosed hereinafter are impurities of Compound 1 which can be later present in the final and crystallized product, Compound A.

Example 1: Preparation of N-(4-chloro-3-(trifluoromethyl)phenyl)-1H-imidazole-1-carboxamide (Compound 1)

     A reactor was loaded with 1,1-carbonyldiimidazole (CDI), 14.92 g, imidazole hydrochloride (1.8 g) and acetone (45 mL), the mixture was cooled to 10 °C and stirred for 30 min. A solution of 4-chloro-3- (trifluoromethyl)aniline (15 g) and imidazole (0.26 g) in acetone (15 mL) was prepared and added to a suspension of CDI at 10 °C. The resulting mixture was stirred for 1 h at this temperature and treated with ethanol (1.1 mL). The resulting mixture was stirred for about 1 h at 10 °C. LCMS of the reaction mixture was performed to observe the impurity with [M-H]- = 457.9878. The estimated structure is indicated in the Table 1.

Table 1 LCMS results of analysis of the reaction mixture



Instrument: Agilent 1100 HPLC (Binary pump)

Column: Zorbax SB-C18, 150x4.6 mm, 1.8 µ

Column Temp: 35 °C

Mobil phase: A (0.1% TFA in water: Acetonitril ,95:5); B (Acetonitril)

Gradient: t(0), B(0); t(5), B(35); t(8), B(50); t(10), B(65); t(15), B(75); t(20), B(75) Stop time: 30 min

Post time: 5 min

Flow rate: 0.8 mL/min

Injection volume: 5 µL