2,4,6-Trichlorobenzoyl chloride → N-(3-cyclopropyl-1-((1-ethyl-1H-pyrazol-3-yl)methyl)-1H-indazol-4-yl)-7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxamide

Participants

Reaction Conditions

Reaction Steps

To lithium 7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxylate (100 mg, 0.316 mmol; prepared as in Example 56, step A) was added NMP (60 mL). The reaction mixture was cooled to 0° C. and 2,4,6-trichlorobenzoyl chloride (50.4 μL, 0.316 mmol) was added dropwise. The cold bath was removed once the addition was complete. The reaction mixture was stirred for 1 hour. The reaction mixture became cloudy. 3-Cyclopropyl-1-((1-ethyl-1H-pyrazol-3-yl)methyl)-1H-indazol-4-amine (59.4 mg, 0.211 mmol) was added and the mixture was heated to 88° C. for 11 hours. The mixture was cooled to ambient temperature. Vacuum distillation was set up and NMP was removed until the reaction mixture became a thick oily residue, to which 10% NaOH aqueous solution (100 mL) was added and the resulting clear solution was stirred at 80° C. for 30 minutes. The mixture was cooled to ambient temperature and extracted with DCM. The organic phases were combined, dried (Na2SO4) and concentrated under vacuum (bath temperature at 80° C. to remove left over NMP) to a thick residue, which was triturated with Et2O (500 mL) to give the final product (80 mg). MS (ES+APCI) m/z=568 (M+H).

Provenance & Evidence