反应详情

温度

20 °C

6-methylpyridin-2-ol (95 mg, 0.87 mmol) was added in one portion to polymer supported triphenylphosphine (1.89 mmol/g; 460 mg, 0.87 mmol) in DCM (5 ml). Di-tert-butyl azodicarboxylate (201 mg, 0.87 mmol) and 4-(4-fluoro-3-(4-hydroxypiperidine-1-carbonyl)benzyl)phthalazin-1(2H)-one (2a) (111 mg, 0.29 mmol) in DCM (1 ml) was added and the resulting mixture was stirred at 20° C. for 4 hours. The reaction mixture was diluted with DCM and washed with water (×2). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by preparative HPLC (Waters XTerra C18 column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% formic acid) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford the desired material as a white solid (10 mg, 7.3% yield); 1H NMR (400.132 MHz, CDCl3) δ 1.70-1.80 (1H, m), 1.85-1.95 (2H, m), 2.02-2.08 (1H, m), 2.41 (3H, s), 3.22-3.28 (1H, m), 3.51-3.57 (1H, m), 3.74-3.83 (1H, m), 3.95-4.03 (1H, m), 4.28 (2H, s), 5.32-5.35 (1H, m), 6.50 (1H, d), 6.69 (1H, d), 7.02 (1H, t), 7.26-7.29 (1H, m), 7.33-7.35 (1H, m), 7.44 (1H, t), 7.71-7.79 (3H, m), 8.45-8.48 (1H, m), 10.33 (1H, s); m/z (LC-MS, ESI+), RT=2.26 (M+H 473.6).

1. washwashed with water (×2)
2. dry with materialThe organic layer was dried over MgSO4
3. filtrationfiltered
4. customevaporated
5. customto afford crude product
6. customThe crude product was purified by preparative HPLC (Waters XTerra C18 column, 5μ silica, 19 mm diameter, 100 mm length)
7. additionFractions containing the desired compound
8. customwere evaporated to dryness