反应详情

温度

0 °C

1-Methylpiperazine (70 μL, 0.63 mmol) is added to a suspension of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-(5-formylthien-3-yl)thieno[3,2-b]pyridine-6-carbonitrile (225 mg, 0.49 mmol) in 4 mL of dichloromethane and 1 mL of N,N-dimethylformamide. The reaction mixture is cooled to 0° C. and sodium triacetoxyborohydride (520 mg, 2.45 mmol) is added. After stirring at 0° C. for 10 minutes, 2 drops of acetic acid are added and the reaction mixture is allowed to warm to room temperature and stirred for 4 hours. The reaction is quenched by the addition of water and then partitioned between saturated aqueous sodium bicarbonate and dichloromethane. The organic layer is washed with water, dried over sodium sulfate, filtered and concentrated in vacuo. The residue is purified by flash column chromatography eluting with 5% methanol in dichloromethane. The fractions containing product are combined and concentrated in vacuo. The residue is washed with diethyl ether to provide 133 mg of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2{5-[(4-methylpiperazin-1-yl)methyl]thien-3-y}thieno[3,2-b]pyridine-6-carbonitrile as white crystals, mp 224-226° C.; 1H NMR (DMSO-d6) δ 2.18 (s, 3H), 2.25-2.55 (m, 8H), 3.68 (s, 2H), 3.85 (s, 3H), 7.35 (s, 1H), 7.37 (s, 1H), 7.74 (s, 1H), 7.75 (s, 1H), 7.82 (s, 1H), 8.58 (s, 1H), 9.68 (s, 1H); MS 523.1, 544.2 (M+H)+.

1. temperatureto warm to room temperature
2. stirringstirred for 4 hours
3. customThe reaction is quenched by the addition of water
4. custompartitioned between saturated aqueous sodium bicarbonate and dichloromethane
5. washThe organic layer is washed with water
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe residue is purified by flash column chromatography
10. washeluting with 5% methanol in dichloromethane
11. additionThe fractions containing product
12. concentrationconcentrated in vacuo
13. washThe residue is washed with diethyl ether