反应详情

3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-bromobenzonitrile (0.193 g, 0.542 mmol), 4-chloro-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxylic acid (0.150 g, 0.542 mmol) and DIPEA (0.189 mL, 1.084 mmol) were combined in THF (2 mL) and treated with HATU (0.227 g, 0.596 mmol) at 25° C. overnight with stirring. The reaction mixture was concentrated to dryness, dissolved in DCM, washed with water, dried over MgSO4, filtered and concentrated to dryness. The residue was dissolved in DCM (2.5 mL) and treated with TFA (2.5 mL) at 25° C. overnight. The reaction mixture was concentrated to dryness, dissolved in DCM, washed with saturated aqueous NaHCO3, dried over MgSO4, filtered and concentrated to dryness. The resultant solid was recrystallized from EtOH, cooled in an ice bath and filtered to give N-({3-[(3-bromo-5-cyanophenyl)oxy]-4-chloro-2-fluorophenyl}methyl)-4-chloro-1H-imidazole-5-carboxamide (0.195 g, 0.403 mmol, 74.3% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 13.18 (br. s., 1H), 8.26 (s, 1H), 7.93 (s, 1H), 7.78 (s, 1H), 7.46-7.60 (m, 3H), 7.37 (t, J=7.69 Hz, 1H), 4.53 (d, J=2.47 Hz, 2H). LC-MS (ES−) m/z 481.04, 483.07 [M−1]. LC-MS (ES+) m/z 482.94, 484.92 [M+H].

1. concentrationThe reaction mixture was concentrated to dryness
2. dissolutiondissolved in DCM
3. washwashed with water
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated to dryness
7. dissolutionThe residue was dissolved in DCM (2.5 mL)
8. additiontreated with TFA (2.5 mL) at 25° C. overnight
9. concentrationThe reaction mixture was concentrated to dryness
10. dissolutiondissolved in DCM
11. washwashed with saturated aqueous NaHCO3
12. dry with materialdried over MgSO4
13. filtrationfiltered
14. concentrationconcentrated to dryness
15. customThe resultant solid was recrystallized from EtOH
16. temperaturecooled in an ice bath
17. filtrationfiltered