Tetrahydrofuran → 1-(3-Bromophenyl)-1-isopropyl-1H-isoindol-3-amine acetate

Participants

Reaction Steps

Isopropyllithium (0.88 mL, 0.616 mmol, 0.7 M in pentane) was drop wise added to N-[(3-bromophenyl)(2-cyanophenyl)methylene]-2-methylpropane-2-sulfinamide (Scheme #5, N) (0.200 g, 0.514 mmol) in tetrahydrofuran (5 mL) at −78° C. The temperature was allowed to rise to −25° C. after 2 h of stirring. The reaction was quenched with water (2 mL) and extracted with ethyl acetate. The organic phase was washed (water and brine), dried over magnesium sulfate and concentrated. The residue was dissolved in methanol (5 mL) and hydrochloric acid (1 mL, 1 M in diethyl ether) was added. The reaction mixture was stirred at room temperature for 18 h and was then concentrated. The residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate. The organic phase was washed (brine), dried over magnesium sulfate and concentrated. Purification by column chromatography using gradient eluation from dichloromethane to dichloromethane: 3.5 M ammonia in methanol 90:10 and preparative HPLC gave 9.0 mg (4.5% yield) of the title compound: 1H NMR (CDCl3) δ 7.97 (d, J=7.83 Hz, 1 H), 7.69 (t, J=1.89 Hz, 1 H), 7.67-7.63 (m, 1 H), 7.61-7.55 (m, 1 H), 7.55-7.45 (m, 2 H), 7.43-7.35 (m, 1 H), 7.22 (t, J=7.96 Hz, 1 H), 2.92-2.77 (m, 1 H), 2.11 (s, 3 H), 1.02 (d, J=6.82 Hz, 3 H), 0.63 (d, J=6.57 Hz, 3 H); MS (ES) m/z 329, 331 [M+1]+.

Provenance & Evidence