反应详情

温度

100 °C

(3-(4-(1H-Pyrazol-1-yl)benzyl)-2,4-dichloro-8-methylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanol (200 mg, 0.321 mmol, Intermediate 68), azetidine (183 mg, 3.21 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 solvent and excess azetidine were removed by reduced pressure distillation. The crude residue was taken up into EtOAc, then extracted twice with a saturated, aqueous NH4Cl solution. 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 C34H29ClF3N7O, 643.2. m/z found, 644.3 [M+H]+. 1H NMR (600 MHz, CDCl3) δ ppm 8.82 (d, J=2.2 Hz, 1H), 7.90-7.86 (m, 2H), 7.85 (d, J=2.5 Hz, 1H), 7.66 (d, J=1.7 Hz, 1H), 7.61-7.58 (m, 1H), 7.58-7.54 (m, 2H), 7.36 (dd, J=2.3, 1.1 Hz, 1H), 7.19-7.15 (m, 2H), 7.14 (d, J=1.1 Hz, 1H), 6.73 (s, 1H), 6.45-6.40 (m, 1H), 6.24 (d, J=1.1 Hz, 1H), 4.29 (s, 2H), 4.13 (t, J=7.5 Hz, 4H), 3.33 (s, 3H), 2.58 (s, 3H), 2.28-2.19 (m, 2H).

1. customsealed
2. temperaturemaintained at that temperature overnight
3. temperatureThe reaction vessel was then cooled to room temperature
4. customthe solvent and excess azetidine were removed by reduced pressure distillation
5. extractionextracted twice with a saturated, aqueous NH4Cl solution
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