Dichloromethane → [2-((S)-1-Aminoethyl)-5-fluoro-3-phenyl-3H-benzoimidazol-4-yl]acetonitrile dihydrochloride

Participants

Reaction Steps

To a suspension of ((S)-1-carbamoylethyl)carbamic acid tert-butyl ester (435 mg, 2.31 mmol) in DCM (5 mL) was added triethyloxonium tetrafluoroborate (369 mg, 1.94 mmol) and the reaction mixture stirred at RT for 2 hours, during which the solids dissolved. The reaction mixture was concentrated in vacuo and the residue dissolved in ethanol (5 mL). (3-Amino-6-fluoro-2-phenylaminophenyl)acetonitrile (223 mg, 0.92 mmol) was added and the reaction heated at 70° C. for 1 h. The reaction mixture was concentrated in vacuo, the residue dissolved in water and the product extracted with EtOAc (3×20 mL). The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, eluting with 0-100% EtOAc in cyclohexane) LCMS (Method C): RT=3.36 min, [M+H]+=395. The product was dissolved in HCl in dioxane (4N, 10 mL) and the reaction stirred at RT for 1 h. The reaction mixture was concentrated in vacuo to give the title product as an off white solid (227 mg, 67%). LCMS (Method C): RT=1.88 min, [M+H]+=295.

Provenance & Evidence