反应详情

温度

-43 °C

To a flask containing 1-methyl-1H-1,2,3-triazole (100 mg, 1.2 mmol) was added THF (10 mL) and the colorless solution was cooled to −43° C. using a CH3CN—CO2 bath. Then, n-BuLi (2.5 M in hexanes, 490 μL, 1.23 mmol) was added dropwise which afforded an opaque mixture. The mixture was stirred at −40° C. for 30 minutes, then a homogeneous solution of (4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanone (255 mg, 0.54 mmol, Intermediate 80: step b) in 2 mL THF was introduced. After 5 minutes, the reaction mixture was then placed in an ice-water bath. The reaction was quenched after 20 minutes with aqueous NH4Cl solution and the aqueous portion was extracted with EtOAc (3×30 mL) and EtOAc:THF (1:1, 30 mL). The combined organics were washed with brine, dried over MgSO4, filtered and concentrated. The solid was triturated with MeOH and filtered to give a yellow filtrate which was concentrated and chromatographed on silica gel (3% MeOH-DCM increasing to 10% MeOH) to afford the title compound. 1H NMR (500 MHz, CDCl3) δ 8.22 (d, J=2.1 Hz, 1H), 7.76 (d, J=8.7 Hz, 2H), 7.49 (d, J=8.1 Hz, 2H), 7.41-7.35 (m, 3H), 7.10 (s, 1H), 6.99 (s, 1H), 6.22 (s, 1H), 4.29 (s, 2H), 4.07 (s, 3H), 3.89 (s, 3H), 3.41 (s, 3H). MS (ESI): mass calcd. for Chemical Formula: C26H22ClF3N6O2; Exact Mass: 542.14. m/z found 542.9 [M+H]+.

1. customafforded an opaque mixture
2. waitAfter 5 minutes
3. customthe reaction mixture was then placed in an ice-water bath
4. customThe reaction was quenched after 20 minutes with aqueous NH4Cl solution
5. extractionthe aqueous portion was extracted with EtOAc (3×30 mL) and EtOAc:THF (1:1, 30 mL)
6. washThe combined organics were washed with brine
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated
10. customThe solid was triturated with MeOH
11. filtrationfiltered
12. customto give a yellow filtrate which
13. concentrationwas concentrated
14. customchromatographed on silica gel (3% MeOH-DCM increasing to 10% MeOH)