Sodium hydride → HCID 136338406, compound

Participants

Reaction Conditions

Reaction Steps

Sodium hydride (0.026 g of 60% suspension in mineral oil, 0.65 mmol) was added to a cooled (0° C.) solution of N-{2-[(4-methylpiperazin-1-yl)sulfonyl]ethyl}-2-oxoindoline-5-carboxamide (0.120 g, 33 mmol) in N,N-dimethylformamide (5 mL). The reaction mixture was stirred at 0° C. for 10 min under an N2 atmosphere, followed by the addition of 2-chloro-5-cyanopyridine (0.050 g, 0.36 mmol) in N,N-dimethylformamide (2 mL). The reaction vessel was closed, immediately warmed up to 100° C., and the reaction was stirred at this temperature for 1 h. The cooled mixture was diluted with a saturated sodium hydrogen carbonate solution (5 mL) and concentrated in vacuo. The residue was suspended in methanol/dichloromethane (1:1), silica gel (˜2 g) was added and mixture was re-concentrated in vacuo. The solid residue was purified on a silica gel column using dichloromethane/methanol/aqueous NH3, (60:10:1), as the eluent. Fractions containing product were concentrated, the resulting orange foam was suspended in ethyl acetate (3 mL), and filtered to give 0.020 g (13% yield) of the title compound as the base. This material was dissolved in chloroform/methanol, (1:1), and treated with HCl in diethyl ether followed by addition of diethyl ether. The resulting yellow crystals were collected by filtration and washed with diethyl ether to afford 0.014 g (60% yield) of the title compound: 1H NMR (DMSO-d6, 300 MHz) δ 14.68 (br s, 1H), 10.94 (s, 1H), 10.55 (br s, 1H), 8.74 (br s, 1H), 8.59 (s, 1H), 8.00 (s, 1H), 7.86 (d, J=9.0 Hz, 1H), 7.70 (d, J=9.0 Hz, 1-H), 7.60 (d, J=8.1 Hz, 1H), 6.98 (d, J=8.1 Hz, 1H), 3.83-3.75 (m, 4H), 3.70-3.62 (m, 2H), 3.52-3.42 (m, 4H), 3.27-3.20 (m, 2H), 3.12-3.05 (m, 2H), 2.75 (s, 3H); MS (ES) m/z 469 (M++1).

Provenance & Evidence