Acetic Acid → N-[(S)-1-(6-Fluoro-1-pyridin-3-yl-1H-benzoimidazol-2-yl)ethyl]acetamide

HRID 242916Notes

Reaction equation

HRID 242916 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]=1

Participants

3

Reactant 2

HCID 176Acetic Acid2×HCID 68158302HCID 68158302, compound2×

Product 1

HCID 68157467N-[(S)-1-(6-Fluoro-1-pyridin-3-yl-1H-benzoimidazol-2-yl)ethyl]acetamideYield 57%

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)

Workup

  1. temperatureAfter cooling to RT
  2. customthe two reaction mixtures
  3. customthe volatiles were removed in vacuo
  4. customThe resulting residue was partitioned between EtOAc
  5. washThe organic fraction was washed with water
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% MeOH in DCM)

Sources & evidence

ORD record
ord-5f24c83c2fd4415485e4d66c943ef46a
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

Loading…