Yield:252003-71-7 82%

Reaction Conditions:

with hydrogenchloride in diethyl ether;ethanol at 20 - 50; for 75 h;Heating / reflux;

Steps:

2

The compound 3-(4-bromo-2,6-difluoro-benzyloxy)-5-[3-(4-pyrrolidin-1-yl-butyl)-ureido]-isothiazole-4-carboxylic acid amide (500 mg, 0.939 mmol) was dissolved in EtOH (20 mL) at reflux, allowed to cool to ambient temperature and treated with HCl (0.94 mL of a 1.0 M solution in Et₂O) while swirling flask. The mixture was then shaken gently with heating at 50° C. for 3 hours and at ambient temperature for 3 days. The solid was filtered, dried under high vacuum to afford a white solid (468 mg, 0.823 mmol, 82%). Melting point 230° C. (DSC). Hygroscopicity: 1% (by weight)) at 90% relative humidity at ambient temperature (RH). Characteristic X-ray powder diffraction peaks (2-theta, [% relative intensity]): 8.623 [90.7], 12.121 [38.9], 17.298 [95.2], 23.397 [44.7], 23.944 [51.7], 24.119 [62.7], 24.873 [55.7], 25.948 [100], and 28.821 [39.6].

References:

US2005/234115,2005,A1 Location in patent:Page/Page column 6