2-(4-Fluorophenyl)acetyl isocyanate → 1-(3-Fluoro-4-(5-methyl-6-(2-(4-methylpiperazin-1-yl)ethoxy)pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)phenyl)-3-(2-(4-fluorophenyl)acetyl)urea, bis-hydrochloride salt

Participants

Reaction Steps

To a solution of 3-fluoro-4-(5-methyl-6-(2-(4-methylpiperazin-1-yl)ethoxy)pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)benzenamine (20 mg, 0.05 mmol, Compound B of Example 45) in 1 mL of THF at room temperature was added a solution of 2-(4-fluorophenyl)acetyl isocyanate in toluene (0.36 M, 0.18 mL, Compound C of Example 4) and the solution was allowed to stir overnight. HPLC analysis and LC-MS analysis indicated the completion of the reaction and the organic solvent was thus removed under reduced pressure. The residue was purified on preparative HPLC. The title compound (15 mg, 46%) was finally obtained as a 2.HCl salt after a work-up similar to that described for Compound D of Example 36. 1H NMR (DMSO-d6) δ 11.02 (s, 1H), 10.58 (s, 1 if), 8.04 (s, 11H), 7.99 (s, 1H), 7.70(d, 1H), 7.35 (m, 4H), 7.16 (m, 2H), 4.44 (br.s, 2H), 3.40–3.70 (m, 12H), 2.81 (s, 3H), 2.39 (s, 3H); MS(ESI+) m/z 580.1 (M+H)+.

Provenance & Evidence