反应详情

温度

100 °C

(3-(4-(1H-Pyrazol-1-yl)benzyl)-2,4-dichloroquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanol (100 mg, 0.164 mmol, Intermediate 65), N,O-dimethylhydroxylamine hydrochloride (327 mg, 2.82 mmol), and dimethylformamide (2 mL) were combined in a reaction tube, which was then sealed and heated to 100° C. for 48 hours. The contents were then cooled, transferred to a separatory funnel, diluted with EtOAc, extracted with a saturated, aqueous NH4Cl solution, then four times with deionized water. The organic phase was separated and dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was purified via reverse phase chromatography using acetonitrile with 0.05% trifluoroacetic acid in water as eluent. The fractions from the purification containing the desired product were transferred to a separatory funnel with EtOAc and extracted with a saturated, aqueous NaHCO3 solution. The aqueous layer was separated, extracted with EtOAc, then the combined organic phases were dried over MgSO4, filtered and concentrated under reduced pressure to afford the title compound. MS (ESI): mass calcd. for C34H33F3N8O3, 658.3. m/z found, 659.3 [M+H]+. 1H NMR (600 MHz, CD3OD) δ 8.75 (d, J=2.1 Hz, 1H), 8.34 (d, J=2.0 Hz, 1H), 8.13 (dd, J=2.5, 0.5 Hz, 1H), 8.01 (dd, J=8.6, 2.7 Hz, 2H), 7.84 (d, J=8.2 Hz, 1H), 7.82 (s, 1H), 7.75 (dd, J=8.9, 2.2 Hz, 1H), 7.69-7.65 (m, 1H), 7.60-7.55 (m, 2H), 7.21 (d, J=8.7 Hz, 2H), 6.48 (dd, J=2.4, 1.9 Hz, 1H), 6.38 (s, 1H), 4.43 (s, 2H), 3.51 (s, 3H), 3.46 (s, 3H), 3.13 (s, 3H), 3.30 (s, 3H), 2.89 (s, 3H).

1. customwhich was then sealed
2. temperatureThe contents were then cooled
3. customtransferred to a separatory funnel
4. extractionextracted with a saturated, aqueous NH4Cl solution
5. customThe organic phase was separated
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe crude material was purified via reverse phase chromatography
10. customThe fractions from the purification
11. additioncontaining the desired product
12. customwere transferred to a separatory funnel with EtOAc
13. extractionextracted with a saturated, aqueous NaHCO3 solution
14. customThe aqueous layer was separated
15. extractionextracted with EtOAc
16. dry with materialthe combined organic phases were dried over MgSO4
17. filtrationfiltered
18. concentrationconcentrated under reduced pressure