2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → N-(2-(2-amino-5-(piperidin-1-yl)phenyl)pyridin-4-yl)-3-(trifluoromethyl)benzamide

Participants

Reaction Conditions

Reaction Steps

Into a 50-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of N-(2-chloropyridin-4-yl)-3-(trifluoromethyl)benzamide (350 mg, 1.16 mmol, 1.00 equiv), 4-(piperidin-1-yl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenamine (430 mg, 1.42 mmol, 1.20 equiv), Pd(PPh3)2Cl2 (81.7 mg, 0.12 mmol, 0.10 equiv), K3PO4.7H2O (790 mg, 2.33 mmol, 2.00 equiv), X—PHOS (91.6 mg, 0.23 mmol, 0.20 equiv) in DME/H2O (10:1) (30/3 mL). The resulting solution was stirred for 2 h at 80° C. The reaction progress was monitored by LCMS. The resulting mixture was concentrated under vacuum. The residual solution was diluted with 50 mL of water. The resulting solution was extracted with 2×50 mL of dichloromethane and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with dichloromethane/methanol (100˜100:1˜40:1). This resulted in 350 mg (67%) of N-(2-(2-amino-5-(piperidin-1-yl)phenyl)pyridin-4-yl)-3-(trifluoromethyl)benzamide as a yellow solid

Provenance & Evidence