反应详情

Diisopropyl azodicarboxylate (0.040 g, 0.20 mmol) was added to a mixture of 5-hydroxynicotinic acid methyl ester (0.038 g, 0.25 mmol), 4-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]butan-1-ol (0.060 g, 0.20 mmol), triphenylphosphine (0.052 g, 0.20 mol) and tetrahydrofuran (3.0 mL) at room temperature with stirring. After 16 h, the solvent was removed in vacuo. The residue was diluted with ethyl acetate (50 mL) and washed with sodium bicarbonate (1×40 mL). The organic solution was concentrated and purified by column chromatography (1.5-5% methanol/dichloromethane) to give 7 mg (8%) methyl 5-4-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]butoxynicotinate as white solid. MS [M+H]=438.1, LC/MS (EI) tR 4.63 min (Method D), 1H NMR (CDCl3) δ (ppm) 9.02 (s, 1H), 8.82 (s, 1H), 8.38 (s, 1H), 7.68 (s, 1H), 7.42-7.35 (m, 2H), 7.34 (s, 1H), 7.20-7.10 (m, 2H), 3.97 (s, 3H), 3.88 (t, J=6.3 Hz, 2H), 2.72 (t, J=7.2 Hz, 2H), 1.81-1.66 (m, 2H), 1.66-1.53 (m, 2H).

1. customthe solvent was removed in vacuo
2. additionThe residue was diluted with ethyl acetate (50 mL)
3. washwashed with sodium bicarbonate (1×40 mL)
4. concentrationThe organic solution was concentrated
5. custompurified by column chromatography (1.5-5% methanol/dichloromethane)