Dichloromethane → 4-(2-(5-fluoro-6-methoxypyridin-3-ylamino)-5-(piperazin-1-ylmethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

Participants

Reaction Steps

A slightly cooled stirred solution of tert-butyl 4-((5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)methyl)piperazine-1-carboxylate (8.77 g, 11.45 mmol) in DCM (25.00 mL, 389 mmol) was treated with TFA (15.00 mL, 195 mmol) and the mixture was stirred at room temperature for 1 h. The mixture was concentrated and the residual sticky material was taken up in DCM (100 mL) and carefully quenched with saturated NaHCO3(aq) until slightly basic. The aqueous layer was extracted with DCM (2×100 mL) and the combined organic layers were washed with brine, dried over Na2SO4, and concentrated to give 4-(2-(5-fluoro-6-methoxypyridin-3-ylamino)-5-(piperazin-1-ylmethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine as a yellow solid. A portion of this solid (0.349 g, 0.524 mmol) was dissolved in DCM (5.00 mL, 78 mmol) and Et3N (0.365 mL, 2.62 mmol) at −15° C. The mixture was treated slowly with dimethylcarbamic chloride (0.169 g, 1.573 mmol) and stirred for 1 h before warming up to room temperature overnight. The reaction mixture was concentrated, the crude product was adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep pre-packed silica gel column (10 to 100% EtOAc in hexanes) to give 4-((5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)methyl)-N,N-dimethylpiperazine-1-carboxamide (0.3555 g, 92%) as a yellow solid (ESI, +ve ion) 736.7 (M+H)+.

Provenance & Evidence