Acetic Acid → 5-(1-Benzyl-piperidin-3-ylamino)-indazole-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

A mixture of 1-benzyl-piperidin-3-one hydrochloride (116 g, 0.52 mol, 1.2 eq) and TEA (43.5 g, 0.43 mol, 1.0 eq) in DCE (800 ml) was stirred at 30° C. for 1 hr. Then 5-amino-indazole-1-carboxylic acid tert-butyl ester (100 g, 0.43 mol, 1.0 eq) and CH3COOH (25.8 g, 0.43 mol, 1.0 eq) were added to the reaction mixture NaBH(OAc)3 (273 g, 1.29 mol, 3.0 eq) was added in one portion after 30 min. The mixture was stirred at 30° C. for 16 hrs. LC-MS showed the reaction was complete. 1 L DCM was added to the reaction mixture and the organic layer was washed with saturated. NaHCO3 (800 ml*3) and H2O (500 ml*3), dried over Na2SO4 and concentrated by rotavapor. The crude product was purified by column chromatography on silica gel using DCM: CH3OH=60:1 to give the 5-(1-benzyl-piperidin-3-ylamino)-indazole-1-carboxylic acid tert-butyl ester (131 g, 75%).

Provenance & Evidence