6-Chloronicotinic acid → 4-[(6-Chloro-pyridine-3-carbonyl)-amino]-4-cyano-piperidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Steps

To a solution of 4-amino-4-cyano-piperidine-1-carboxylic acid tert-butyl ester (0.527 g, 2.34 mmol, 1.0 equiv; prepared as described in WO 03/104 236 A1 (Bristol-Myers Squibb Company); [CAS RN 331281-25-5]) in anhydrous THF (12 mL) and N-ethyl diisopropylamine (0.48 mL) was added in the presence of (benzotriazol-1-yloxy)-tris-(dimethylamino)phosphonium hexafluorophosphate (1.138 g, 2.58 mmol, 1.1 equiv; BOP reagent) 6-chloro-nicotinic acid (0.369 g, 2.34 mmol, 1.0 equiv) and the reaction mixture stirred at rt for 12 h. The reaction mixture was poured on crashed ice/NH4Cl, extracted with ethyl acetate (2×200 mL) and the combined organic phases washed with a sat. solution of NaCl (2×100 mL) and water (2×100 mL). The organic phase was dried over Na2SO4, concentrated by evaporation under reduced pressure and the crude material purified by silica column chromatography eluting with a mixture of ethyl acetate/triethylamine (97:3) providing 0.63 g (74%) of the title compound as off-white solid. MS (ISP): 365.1 [M+H]+

Provenance & Evidence