反应详情

温度

100 °C

{2,4-Dichloro-3-[4-(1H-pyrazol-1-yl)benzyl]quinolin-6-yl}(2,6-dimethylpyridin-3-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol (198 mg, 0.347 mmol, Example 151), azetidine (70 μL, 1.04 mmol), and DMF (2 mL) were combined in a reaction tube, then sealed and heated to 100° C. and maintained at that temperature for 24 hours. The residue was taken up into EtOAc, transferred to a reparatory funnel and extracted twice with a saturated, aqueous NH4Cl solution. The organic phase was separated then 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 C33H31ClN8O, 590.2. m/z found, 591.5 [M+H]+. 1H NMR (400 MHz, CDCl3) δ ppm 8.07-8.02 (m, 1H), 7.78 (d, J=8.4 Hz, 1H), 7.64-7.56 (m, 2H), 7.38-7.31 (m, 1H), 7.08-6.99 (m, 4H), 6.98 (s, 1H), 6.88-6.77 (m, 2H), 5.89 (d, J=1.9 Hz, 1H), 4.29 (s, 2H), 4.12 (t, J=7.5 Hz, 4H), 3.93 (s, 3H), 2.47 (s, 3H), 2.34 (s, 3H), 2.31-2.18 (m, 2H).

1. customsealed
2. temperaturemaintained at that temperature for 24 hours
3. customtransferred to a reparatory funnel
4. extractionextracted twice with a saturated, aqueous NH4Cl solution
5. customThe organic phase was separated
6. dry with materialthen dried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe crude material was purified via reverse phase chromatography