4-Aminobenzonitrile → HCID 59190809, compound

Participants

Reaction Conditions

Reaction Steps

3-Nitrophenyl-propionic acid (992 mg, 5.08 mmol) was suspended in toluene (10 mL). Thionyl chloride (1.82 mL, 25.0 mmol) was added dropwise and the resulting mixture was stirred at 110° C. for 1 h. The reaction mixture was concentrated and the residue was dissolved in dry dichloromethane (15 mL). To this solution was added 4-aminobenzonitrile (590 mg, 5.2 mmol) and Hunig's base (1.85 mL, 10.0 mmol). The reaction mixture was stirred for 4 h then diluted with ethyl acetate (150 mL) and quenched with NH4Cl (150 mL satd. aq.) The organic fraction was isolated and washed with brine (50 mL), dried with MgSO4 and concentrated. The residue was purified by flash chromatography using an ethyl acetate/hexane gradient to provide 1.273 g of N-(4-cyano-phenyl)-3-(3-nitro-phenyl)-propionamide (85% yield). This intermediate (103 mg, 0.35 mmol) was dissolved in methanol (5 mL) under an atmosphere of argon, and sodium borohydride (26.3 mg, 0.7 mmol) and Pd/C (20 mg) were added. The resulting mixture was stirred at room temperature for 1 h, filtered through celite, and concentrated. The residue was suspended in NH4Cl (20 mL, saturated aqueous), and this mixture was extracted with ethyl acetate (2×20 mL). The combined organic fractions were washed with brine (20 mL), dried and concentrated to provide 3-(3-amino-phenyl)-N-(4-cyano-phenyl)-propionamide (80 mg, 87% yield) which was used without further purification. This intermediate was converted to the title compound as described in example 20. MS, electrospray, 405 (M+H).

Provenance & Evidence