2-Chloroaniline → HCID 66926929, compound

Participants

Reaction Steps

A 1 M solution of lithium bis(trimethylsilyl)amide (0.573 mL, 0.573 mmol) was added to a solution of 2,3-dichloro-5-(3-methoxyphenyl)isonicotinonitrile (40 mg, 0.143 mmol, from Step 3 of Example 128) and 2-chloroaniline (36.6 mg, 0.287 mmol) in THF (2 mL) at room temperature. After 1 h at room temperature, LCMS and HPLC analysis indicated that a 1:2 mixture of two products were formed. The reaction mixture was quenched with saturated sodium bicarbonate (5 mL) and diluted with ethyl acetate (60 mL), washed with water (5 mL), brine (5 mL), dried (MgSO4) and concentrated. Silica gel chromatography, loading with dichloromethane-hexanes (1:1) and eluting with 5-20% ethyl acetate in hexanes, gave 3-chloro-2-(2-chlorophenylamino)-5-(3-methoxyphenyl)isonicotinonitrile as yellow solid (11 mg, 21% yield). 1H NMR (400 MHz, CDCl3) δ ppm 8.51-8.63 (1H, m), 8.35 (1H, s), 7.87 (1H, s), 7.38-7.51 (2H, m), 7.29-7.37 (1H, m), 6.97-7.16 (4H, m), 3.88 (3H, s); MS (ES+) m/z: 370 (M+H); LC retention time: 4.28 min (analytical HPLC Method A). The minor product was found to be 2-chloro-3-(2-chlorophenylamino)-5-(3-methoxyphenyl)isonicotinonitrile.

Provenance & Evidence