[(S)-1-(2-Benzylamino-4-fluorophenylcarbamoyl)ethyl]carbamic acid tert-butyl ester → [(S)-1-(1-Benzyl-6-fluoro-1H-benzoimidazol-2-yl)ethyl]carbamic acid tert-butyl ester

HRID 243119Notes

Reaction equation

[C:1]([O:5][C:6](=[O:28])[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][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH3:9])([CH3:4])([CH3:3])[CH3:2]>C(O)(=O)C>[C:1]([O:5][C:6](=[O:28])[NH:7][C@H:8]([C:10]1[N:19]([CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:13]2[CH:14]=[C:15]([F:18])[CH:16]=[CH:17][C:12]=2[N:11]=1)[CH3:9])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 70 °C

Procedure

[(S)-1-(2-Benzylamino-4-fluorophenylcarbamoyl)ethyl]carbamic acid tert-butyl ester (1.7 g, 4.39 mmol) was dissolved in acetic acid (15 mL) and heated at 70° C., overnight, under an atmosphere of nitrogen. The reaction mixture was then heated at 80° C. for 6 h. The resultant mixture was allowed to cool to RT and was concentrated in vacuo. The residue was purified by column chromatography (silica gel, gradient 0-50% EtOAc in cyclohexane) to afford the title compound as an off-white solid (0.88 g, 55%). 1H NMR (CDCl3, 400 MHz): δ 7.68 (1H, dd, J=8.81, 4.79 Hz), 7.34-7.26 (3H, m), 7.08-6.95 (3H, m), 6.90 (1H, dd, J=8.69, 2.43 Hz), 5.43 (2H, d, J=5.40 Hz), 5.18-5.06 (1H, m), 1.53 (3H, d, J=6.73 Hz), 1.37 (9H, s).

Workup

temperatureThe reaction mixture was then heated at 80° C. for 6 h
temperatureto cool to RT
concentrationwas concentrated in vacuo
customThe residue was purified by column chromatography (silica gel, gradient 0-50% EtOAc in cyclohexane)

Sources & evidence

ORD record: ord-38201afbbc204e6a9c176ce347648dec
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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