Cesium carbonate → 5-(5-(4-(Difluoromethoxy)phenyl)pyrimidin-2-ylamino)nicotinic acid

Participants

Reaction Conditions

Reaction Steps

A vial is charged with methyl 5-aminonicotinic acid 18 (1.45 mmol), 2-chloro-5-(4-(difluoromethoxy)phenyl)pyrimidine 17 (1.45 mmol), Pd(OAc)2 (0.22 mmol), xanthphos (0.22 mmol), Cs2CO3 (1.45 mmol) and anhydrous 1,4-dioxane (5 mL). The vial is evacuated and refilled with N2 twice and the mixture is heated in an oil bath at 100° C. for 3 h. The vial is cooled down to it and the reaction mixture is diluted with water (20 mL) and pH neutralized with 10% Na2CO3. The resulting suspension is extracted with DCM:IPA=3:1 (3×50 mL). The organic layer is washed once with brine and dried over Na2SO4. The solvent is removed in vacuum and the orange crude is purified by preparative HPLC (MeCN gradient 20-70%) to afford 5 5-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)nicotinic acid 19. MS (m/z) (M+1)+: 359.1.

Provenance & Evidence