反应详情

温度

20 °C

To a solution of 4-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-12-[1-methyl-5-(piperidin-3-yl)-1H-pyrazol-4-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1(14), 2,4,10,12-pentaene (140 mg, 0.300 mmol) and acetone (174 mg, 3.0 mmol) in ethanol (10 mL) was added Ti(Oi-Pr)4 (171 mg, 0.60 mmol). After being stirred at 20° C. for 20 min, NaBH3CN (37 mg, 0.60 mmol) was added and stirred at 20° C. for 24 h. The solvent was removed and several drops of water were added. The solid was filtered off and the filtrate was evaporated to afford the crude product, which was purified prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/1% formic acid, 17 min) to give racemic 268 (45 mg, 29% yield). LCMS (ESI): RT=5.41 min, m/z: 515.3 [M+H+]. 1H NMR (500 MHz, DMSO-d6) δ 8.40 (d, J=8.0 Hz, 1H), 7.91 (s, 1H), 7.43 (s, 1H), 7.09 (dd, J=8.5, 1.5 Hz, 1H), 6.94 (s, 1H), 5.90-5.82 (m, 1H), 4.53 (s, 4H), 3.90 (s, 3H), 3.11 (m, 1H), 3.10-2.66 (m, 3H), 2.50 (t, J=2.0 Hz, 1H), 2.26 (s, 3H), 2.08 (m, 1H), 1.80-1.20 (m, 10H), 0.95-0.92 (m, 6H)

1. stirringstirred at 20° C. for 24 h
2. customThe solvent was removed
3. additionseveral drops of water were added
4. filtrationThe solid was filtered off
5. customthe filtrate was evaporated
6. customto afford the crude product, which
7. customwas purified prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/1% formic acid, 17 min)