Chloroacetaldehyde → 4-(2-{5-[3-(3-Fluoro-phenyl)-2-oxo-imidazolidin-1-yl]-2-methyl-phenylamino}-oxazol-5-yl)-benzonitrile

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Reaction Steps

To a solution of 4-[2-(5-Amino-2-methyl-phenylamino)-oxazol-5-yl]-benzonitrile (558 mg, 2 mmol) and chloroacetaldehyde (50 wt. % in water, 628 mg, 4 mmol) in acetonitril (60 mL), was added at RT NaBH3CN (253 mg, 4 mmol) and dropwise acetic acid (0.4 mL). The mixture was stirred at room temperature 1 h. Ethyl acetate (50 mL) and saturated aqueous NaHCO3 (50 mL) were added. The organic layer was washed with brine (20 mL), dried over MgSO4 and concentrated to give a yellow solid. This was dissolved in toluene (40 mL) and treated with 1-Fluoro-3-isocyanato-benzene (274 mg, 2 mmol) at reflux for 2 h. After evaporation of solvent under reduced vacuum, the crude product was dissolved in isopropanol (60 mL) and treated with potassium tert-butoxide (1.8 g, 16 mmol) at RT for 5 h. Water (20 mL) was added, the organic layer was separated dried over MgSO4 and concentrated. The crude product was silica gel column chromatographed (dichloromethane/ethanol: 95/5) to give 408 mg (45%) of the title compound as a beige solid.

Provenance & Evidence