反应详情

温度

100 °C

{2,4-Dichloro-3-[4-(1H-pyrazol-1-yl)benzyl]quinolin-6-yl}(1-methyl-1H-imidazol-5-yl)pyrimidin-2-ylmethanol (200 mg, 0.328 mmol, Intermediate 65), 3-methoxyazetidine hydrochloride (427 mg, 3.28 mmol), and DMF (2 mL) were combined in a reaction tube, then sealed and heated to 100° C. and maintained at that temperature overnight. The reaction vessel was then cooled to room temperature and the contents were transferred to a separatory funnel with EtOAc dilution, and extracted once with saturated, aqueous NH4Cl solution, then extracted three times with deionized water. The organic phase was separated, dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was purified via reverse phase chromatography using acetonitrile with ammonium hydroxide in water as eluent to provide the title compound. MS (ESI): mass calcd. for C34H29ClF3N7O2, 659.2. m/z found, 660.3 [M+H]+. 1H NMR (600 MHz, CD3OD) δ ppm 8.78 (d, J=2.1 Hz, 1H), 8.11 (dd, J=2.5, 0.4 Hz, 1H), 8.07 (d, J=2.1 Hz, 1H), 8.01 (dd, J=8.2, 2.1 Hz, 1H), 7.80 (d, J=8.2 Hz, 1H), 7.77-7.73 (m, 2H), 7.67 (d, J=1.4 Hz, 1H), 7.62-7.59 (m, 2H), 7.59-7.56 (m, 1H), 7.17 (d, J=8.7 Hz, 2H), 6.49-6.46 (m, 1H), 6.37 (s, 1H), 4.34-4.29 (m, 4H), 4.19-4.13 (m, 1H), 4.02-3.97 (m, 2H), 3.48 (s, 3H), 3.22 (s, 3H).

1. customsealed
2. temperaturemaintained at that temperature overnight
3. temperatureThe reaction vessel was then cooled to room temperature
4. extractionextracted once with saturated, aqueous NH4Cl solution
5. extractionextracted three times with deionized water
6. customThe organic phase was separated
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe crude material was purified via reverse phase chromatography