2,4,6-Trichlorobenzoyl chloride → N-(3-ethyl-1-((5-fluoropyridin-2-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 (0.108 g, 0.331 mmol) was added NMP (2 mL). The mixture was stirred with warming under nitrogen to form a solution. The solution was cooled to 0° C. and 2,4,6-trichlorobenzoyl chloride (0.0518 ml, 0.324 mmol) was added drop wise. The mixture was stirred for one hour at ambient temperature. 3-Ethyl-1-((5-fluoropyridin-2-yl)methyl)-1H-indazol-4-amine (0.064 g, 0.237 mmol) was then added and the reaction mixture heated to 88° C. for 16 hours. The mixture was allowed to cool and then concentrated under reduced pressure to remove the majority of the NMP. To this residue was added a 10% aqueous solution of sodium hydroxide (5 mL). The resulting clear solution was stirred at 80° C. for 30 minutes and then cooled to ambient temperature. The mixture was extracted multiple times with DCM. The combined organic phases were dried (sodium sulfate) and concentrated under reduced pressure (bath temperature at 80° C. to remove remaining NMP). To the resulting residue was added ether in order to triturate. The resulting solids were collected by filtration, dissolved in DCM and subjected to purification on silica using a Biotage system, eluting with a gradient of 1-10% 7N NH3 in MeOH/DCM. The resulting product was triturated with ether containing a small amount of DCM to give N-(3-ethyl-1-((5-fluoropyridin-2-yl)methyl)-1H-indazol-4-yl)-7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxamide (23 mg). MS (APCI) m/z=557.1 (M+H).

Provenance & Evidence