反应详情

Sodium hydride (60% dispersion in mineral oil, 38 mg, 0.96 mmol) was added to a solution of N,N-dimethylethanolamine (63 mg, 0.71 mmol) in DMF (5 mL) and the mixture stirred at ambient temperature for 75 minutes. 6-(4-chloro-pyridin-3-yl)-3-(1-methyl-1H-pyrazol-4-yl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole (85 mg, 0.24 mmol) was added and the reaction mixture was stirred at ambient temperature for 26 h then at 80° C. for 2 h. After this time, the reaction mixture was added to a solution of N,N-dimethylethanolamine (0.48 mL) and sodium hydride (60% dispersion in mineral oil, 288 mg) in DMF (2 mL), which had been pre-stirred for 15 minutes. The reaction mixture was stirred at 80° C. overnight before being poured onto water and the resultant solid collected by filtration. The material was purified by flash chromatography (silica, 12 g column, ISCO, 0-20% methanol in DCM then 20% (2N ammonia in methanol) in DCM) to afford the title compound as a yellow oil which crystallised on standing (0.1 g, 58%). 1H NMR (CD3OD, 400 MHz): 8.94 (d, J=1.1 Hz, 1H), 8.81-8.77 (m, 2H), 8.71 (s, 1H), 8.58 (d, J=1.1 Hz, 1H), 8.48 (d, J=5.9 Hz, 1H), 8.09 (s, 1H), 7.94 (s, 1H), 7.28 (d, J=5.9 Hz, 1H), 4.42 (t, J=5.2 Hz, 2H), 3.98 (s, 3H), 3.03 (t, J=5.1 Hz, 2H), 2.42 (s, 6H). LCMS (Method A): RT=3.93 min, M+H+=414.

1. stirringthe reaction mixture was stirred at ambient temperature for 26 h
2. waitat 80° C. for 2 h
3. stirringhad been pre-stirred for 15 minutes
4. stirringThe reaction mixture was stirred at 80° C. overnight
5. additionbefore being poured onto water
6. filtrationthe resultant solid collected by filtration
7. customThe material was purified by flash chromatography (silica, 12 g column, ISCO, 0-20% methanol in DCM