反应详情

4-chloro-N-({4-chloro-3-[(3-cyano-5-cyclopropylphenyl)oxy]-2-fluorophenyl}methyl)-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide (0.132 g, 0.230 mmol) was dissolved in DCM (3 mL) and treated with TFA (3 mL) at 25° C. for 3 days. The reaction mixture was concentrated to dryness and partitioned between DCM and saturated aqueous NaHCO3. The organic phase was isolated, dried over MgSO4, filtered and concentrated to dryness. The residue was purified on 40 g silica gel eluted with 0 to 10% CH3OH/DCM to give 4-chloro-N-({4-chloro-3-[(3-cyano-5-cyclopropylphenyl)oxy]-2-fluorophenyl}methyl)-1H-imidazole-5-carboxamide (0.0705 g, 0.158 mmol, 68.8% yield) as a white foam. 1H NMR (400 MHz, DMSO-d6) δ ppm 13.19 (br. s., 1H), 8.26 (br. s., 1H), 7.78 (s, 1H), 7.31-7.55 (m, 2H), 7.27 (br. s., 1H), 7.09 (s, 2H), 4.53 (d, J=1.39 Hz, 2H), 1.91-2.07 (m, 1H), 0.99 (m, 2H), 0.77 (m, 2H). LC-MS (ES−) m/z 443.18, 445.11 [M−1]. LC-MS (ES+) m/z 445.07, 447.08 [M+H].

1. concentrationThe reaction mixture was concentrated to dryness
2. custompartitioned between DCM and saturated aqueous NaHCO3
3. customThe organic phase was isolated
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated to dryness
7. customThe residue was purified on 40 g silica gel
8. washeluted with 0 to 10% CH3OH/DCM