Acetic Acid → N-[(S)-1-(6-Fluoro-1-pyridin-3-yl-1H-benzoimidazol-2-yl)ethyl]acetamide
Reaction equation
C([O:5][C:6](=O)[NH:7][C@H:8]([C:10](=O)[NH:11][C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:13]=1[NH:19][C:20]1[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=1)[CH3:9])(C)(C)C.[CH3:28]C(O)=O>>[F:18][C:15]1[CH:16]=[CH:17][C:12]2[N:11]=[C:10]([C@@H:8]([NH:7][C:6](=[O:5])[CH3:28])[CH3:9])[N:19]([C:20]3[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=3)[C:13]=2[CH:14]=1Participants
3
Conditions
- Temperature
- 100 °C
Procedure
A solution of {(S)-1-[4-fluoro-2-(pyridin-3-ylamino)phenylcarbamoyl]ethyl}carbamic acid tert-butyl ester (47 mg, 0.126 mmol) in AcOH (1 mL) was heated at 100° C. for 28 h in a sealed tube. In a separate vial, {(S)-1-[4-fluoro-2-(pyridin-3-ylamino)phenylcarbamoyl]ethyl}carbamic acid tert-butyl ester (228 mg, 0.61 mmol) was dissolved in AcOH (2 mL) and heated at 100° C. for 17 h. After cooling to RT, the two reaction mixtures were combined and the volatiles were removed in vacuo. The resulting residue was partitioned between EtOAc and a saturated aqueous solution of NaHCO3. The organic fraction was washed with water, followed by brine, dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% MeOH in DCM) to afford the title compound as an orange oil (126 mg, 57%). LCMS (Method C): RT 2.16 min [M+H]+ 299.3. 1H NMR (CDCl3, 400 MHz): δ 8.84 (1H, dd, J=4.82, 1.02 Hz), 8.75 (1H, s), 7.95 (1H, s), 7.72-7.57 (2H, m), 7.47 (1H, s), 7.07 (1H, td, J=9.15, 2.31 Hz), 6.80 (1H, d, J=8.61 Hz), 5.21-5.09 (1H, m), 1.96 (3H, s), 1.50 (3H, d, J=6.99 Hz)