1-(chloromethyl)piperidin-2-one

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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. 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 concentrate Purify the residue on an ISCO RediSep 35 gram silicagel cartridge eluting with 5% methanol in ethyl acetate Combined product containing fractions concentrate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound is prepared in accordance with the procedures set forth in Moreira, R. et al., Tet. Lett. , (1994), 35, 7107–7110. Thus, a mixture of 2-piperidinone (1.0 g, 10.09 mmol) and paraformaldehyde (500 mg) is refluxed in anhydrous THF (30 mL) and chlorotrimethylsilane (30 mL) overnight under N2. Concentrate the solvent under vacuum to give N-(chloromethyl)-2-piperidone as an oil (1.30 g). The title compound is prepared in accordance with the procedures Concentrate the solvent under vacuum

Conditions: temp:0.00; pressure:0.00; stir: