反应详情

A ˜−70° C. solution of 6-iodo-3-phenyl-2,4-bis(trifluoromethyl)quinoline (152 mg, 0.326 mmol; Intermediate 8, step d) in THF (0.322 mL) was treated with iPrMgCl (2.06 M in THF; 0.158 mL, 0.326 mmol) dropwise via syringe under argon over the course of 30 sec to provide an amber solution that became a yellow opaque slurry within 2 min. After 2 additional min the dark yellow opaque slurry was removed from the cold bath and immediately treated rapidly dropwise with a pre-formed solution of bis(1-methyl-1H-1,2,3-triazol-5-yl)methanone (74.2 mg, 0.386 mmol; Intermediate 57) in THF (2.6 mL) over 45 sec. The reaction was stirred at room temperature for 3 hours and was then quenched with 5 M NH4Cl (1 mL). The aqueous layer was extracted with MTBE (1×3 mL), and the combined organic layers were dried (Na2SO4), filtered, and concentrated. The residue was dry load flash chromatographed with a heptane to 80% EtOAc/heptane gradient to provide the title compound as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.45 (d, J=8.59 Hz, 1H), 8.29 (br. s., 1H), 8.21 (s, 1H), 7.87 (d, J=9.09 Hz, 1H), 7.40-7.56 (m, 5H), 7.29 (s, 2H), 3.87 (s, 6H). MS m/e 534.2 [M+H]+.

1. customto provide an amber solution that
2. customwithin 2 min
3. customAfter 2 additional min the dark yellow opaque slurry was removed from the cold bath
4. customwas then quenched with 5 M NH4Cl (1 mL)
5. extractionThe aqueous layer was extracted with MTBE (1×3 mL)
6. dry with materialthe combined organic layers were dried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was dry load flash
10. customchromatographed with a heptane to 80% EtOAc/heptane gradient