反应详情

To a flask containing azetidin-3-yl(4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol (140 mg, 0.27 mmol, Intermediate 66: step d) was added dichloromethane (8 mL) which gave a suspension at room temperature. Et3N (0.13 mL, 0.9 mmol) was added, followed by acetic anhydride (0.3 mL, 0.32 mmol). After stirring at room temperature for 4 h, more Et3N (200 μL) was added along with more acetyl chloride (25 μL) and the suspension was heated to 35° C. for 18 h. The reaction was quenched with the addition of 1N NaOH (2 mL) and water (5 mL). The aqueous portion was extracted with dichloromethane (3×25 mL). The combined organics were dried over MgSO4, filtered and concentrated. The crude material was chromatographed on silica gel (5% MeOH-dichloromethane) to give the title compound (88 mg) as an off white solid. 1H NMR (500 MHz, CD3CN, racemate) δ 8.25 (dd, J=14.0, 1.9 Hz, 1H), 7.74 (dd, J=8.7, 2.6 Hz, 1H), 7.66 (d, J=4.4 Hz, 1H), 7.58-7.49 (m, 2H), 7.48-7.33 (m, 3H), 5.17 (s, 0.5H), 5.06 (s, 0.5H), 4.43-4.28 (m, 3H), 4.22-4.10 (m, 1H), 4.07-3.98 (m, 4H), 3.93 (dd, J=9.9, 6.0 Hz, 1H), 3.82 (dd, J=9.1, 5.6 Hz, 1H), 3.72 (t, J=8.6 Hz, 1H), 3.65-3.48 (m, 5H). MS (ESI) 560.1 [M+H]+.

1. customgave a suspension at room temperature
2. temperaturethe suspension was heated to 35° C. for 18 h
3. customThe reaction was quenched with the addition of 1N NaOH (2 mL) and water (5 mL)
4. extractionThe aqueous portion was extracted with dichloromethane (3×25 mL)
5. dry with materialThe combined organics were dried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated
8. customThe crude material was chromatographed on silica gel (5% MeOH-dichloromethane)