(R)-tert-butyl 3-(2-(5-(2,6-difluorophenyl)-1H-indol-3-yl)pyrimidin-4-ylamino)piperidine-1-carboxylate → (R)-2-(5-(2,6-difluorophenyl)-1H-indol-3-yl)-N-(piperidin-3-yl)pyrimidin-4-amine

Participants

Reaction Steps

A solution of (R)-tert-butyl 3-(2-(5-(2,6-difluorophenyl)-1-tosyl-1H-indol-3-yl)pyrimidin-4-ylamino)piperidine-1-carboxylate (500 mg, 0.757 mmol) in dioxane (10 mL) was treated with aqueous 1N NaOH (5 mL) and heated at 100° C. for 2 h. The resulting mixture was cooled to RT, and quenched with ice cold water. The resulting precipitate was collected by filtration, washed with ice cold water and dried to obtain the pure (R)-tert-butyl 3-(2-(5-(2,6-difluorophenyl)-1H-indol-3-yl)pyrimidin-4-ylamino)piperidine-1-carboxylate (350 mg, 92%). (R)-tert-butyl 3-(2-(5-(2,6-difluorophenyl)-1H-indol-3-yl)pyrimidin-4-ylamino)piperidine-1-carboxylate (350 mg, 0.69 mmol) was treated with ethanolic HCl (10 mL). The reaction mixture was stirred at RT for 16 h and then extracted with DCM. The combined organic layers were dried; filtered and concentrated to give the crude product, which was purified by recrystallization using 10% MeOH in CHCl3 to yield (R)-2-(5-(2,6-difluorophenyl)-1H-indol-3-yl)-N-(piperidin-3-yl)pyrimidin-4-amine MS (ESI, pos. ion) m/z: 406 (M+1).

Provenance & Evidence