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

Participants

Reaction Conditions

Reaction Steps

Cyclopropylmagnesium bromide (7.20 mL, 3.60 mmol, 0.5 M in tetrahydrofuran) was added drop wise to N-[(3-bromophenyl)(2-cyanophenyl)methylene]-2-methylpropane-2-sulfinamide (Scheme #5, N) (1.00 g, 2.57 mmol) in dry tetrahydrofuran (10 mL) at room temperature under argon atmosphere. The reaction was heated to 30° C. and stirred for 2.5 h, then cooled to 0° C. The reaction was quenched with methanol (5 mL) and extracted twice with ethyl acetate. The organic phases were pooled, washed (saturated aqueous ammonium chloride and water), dried over magnesium sulfate and concentrated. Column chromatography using gradient solution from dichloromethane to dichloromethane:3.5 M ammonia in methanol 97:3 followed by preparative HPLC (Column: Gemini C8; Mobile phase: 35% acetonitrile in 0.1 M ammonium acetate/water; Flow: 1 mL/min) afforded 0.108 g (11% yield) of the title compound: 1H NMR (DMSO-d6) δ 7.72-7.69 (m, 1 H), 7.62-7.57 (m, 3 H), 7.40-7.35 (m, 3 H), 7.25 (t, J=7.78 Hz, 1 H), 1.89 (s, 3 H), 1.86-1.81 (m, 1 H), 0.46-0.35 (m, 2 H), 0.21-0.13 (m, 1 H), −0.09-−0.02 (m, 1 H); MS (ES) m/z 327, 329 [M+1]+.

Provenance & Evidence