1-(Chloromethyl)piperidin-2-one → 3-(Pyridin-4-ylamino)-1H-indole-2-carboxylic acid 2-oxo-piperidin-1-ylmethyl ester

Participants

Reaction Conditions

Reaction Steps

Heat at 50° C. a suspension of 3-(4-pyridinylamino)-1H-indole-2-carboxylic acid potassium salt (1.6 g, 5.49 mmol) in anhydrous THF (30 mL) in an oil bath for 20 min. Add a solution of N-(chloromethyl)-2-piperidone (850 mg, 5.76 mmol) in anhydrous THF (5 mL) dropwise. After 30 min, cool the reaction to ambient temperature. Add water (100 mL), and extract with ethyl acetate (3×100 mL). Combine the organic layers, wash with NaHCO3 (sat), water, brine, dry with MgSO4 and then concentrate. Purify the residue on an ISCO RediSep 35 gram silicagel cartridge, eluting with 5% methanol in ethyl acetate then 20% methanol in ethyl acetate. Combined product containing fractions and, concentrate to give the title compound as a white solid (520 mg, 26%): MS 365 (M+H), TLC (silica gel, MeOH/EtOAc 25:75) Rf=0.18, 1H NMR (DMSO-d6) δ 11.77 (1H, s), 8.46 (1H, s), 8.08 (2H, d, J=5.7 Hz), 7.50 (3H, m), 7.09 (1H, m), 6.58 (2H, d, J=6 Hz), 5.54 (2H, s), 3.27 (2H, br2), 2.23 (2H, brs), 1.66 (4H, brs). 13C NMR (DMSO-d6) δ 170.00, 160.43, 152.25, 149.44, 135.54, 125.60, 122.96, 121.84, 120.22, 119.87, 118.99, 113.00, 108.59, 70.99, 47.00, 31.99, 22.39, 20.60.

Provenance & Evidence