反应详情

n-BuLi (1.63 M in hexane, 0.139 mL, 0.226 mmol) was added dropwise over 1 minute to a solution of 6-bromo-4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline (90.1 mg, 0.209 mmol, Intermediate 12: step d in THF (2.1 mL) at ˜−70° C. under argon. After 2 additional minutes, a homogeneous solution of bis(1-methyl-1H-1,2,3-triazol-5-yl)methanone (41.4 mg, 0.215 mmol, Intermediate 13) in THF (2.1 mL) was added dropwise over 1 minute, and the resulting solution was allowed to warm to room temperature overnight as the dry ice/acetone bath expired. The resulting homogeneous yellow reaction was then quenched with 5 M aqueous NH4Cl (0.06 mL), dried (Na2SO4), filtered, and concentrated to dryness. The residue was purified by C18 HPLC (20% to 100% CH3CN, with 0.1% TFA throughout) and the lyophilisate neutralized with 9:1 DCM/MeOH) and 2 M aqueous K2CO3. The organic layer was dried (Na2SO4), filtered, and concentrated to dryness to provide the title compound as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.16 (d, J=2.02 Hz, 1H), 7.99 (br. s., 1H), 7.91 (d, J=8.59 Hz, 1H), 7.65 (d, J=8.08 Hz, 2H), 7.41-7.51 (m, 3H), 7.19 (s, 2H), 4.36 (s, 2H), 4.04 (s, 3H), 3.84 (s, 6H); MS m/e 544.1 [M+H]+.

1. customat ˜−70° C.
2. customThe resulting homogeneous yellow reaction
3. customwas then quenched with 5 M aqueous NH4Cl (0.06 mL)
4. dry with materialdried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated to dryness
7. customThe residue was purified by C18 HPLC (20% to 100% CH3CN, with 0.1% TFA throughout)
8. dry with materialThe organic layer was dried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated to dryness