反应详情

Diisopropylethylamine (0.210 mL, 1.20 mmol), cyclopropylamine (0.090 mL, 1.3 mmol) and (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (205 mg, 0.460 mmol) are added successively to a stirred suspension of 2-{5-chloro-2-[3-(4-methyl-piperazin-1-yl)-propylamino]-pyrimidin-4-yl}-benzo[b]thiophene-6-carboxylic acid tri-hydrochloride. (195 mg, 0.400 mmol) and LiCl (187 mg, 4.40 mmol) in DMF (4 mL) at ambient temperature under nitrogen, the resultant mixture is heated at 50° C. for 20 hours. After cooling to ambient temperature, the solvent is removed and the residue is subject to chromatography on silica gel, eluting with 2 M NH3/MeOH in dichloromethane 0-8%, to give the free base of the title compound (97 mg). ES+(m/z) 485 (35Cl) and 487 (37Cl) [M+H]. Using the method of Preparation (E) in 2-{5-chloro-2-[3-(4-methylpiperazin-1-yl)-propylamino]-pyrimidin-4-yl}-benzo[b]thiophene-4-carboxylic acid cyclopropylamide tri-hydrochloride, the free base is converted to the tri-hydrochloride salt as a yellow solid.

1. customthe solvent is removed
2. washeluting with 2 M NH3/MeOH in dichloromethane 0-8%