N-[(3-bromophenyl)(2-cyanophenyl)methylene]-2-methylpropane-2-sulfinamide → 1-(3-Bromophenyl)-1-isopropyl-1H-isoindol-3-amine hydrochloride

Participants

Reaction Conditions

Reaction Steps

Isopropylmagnesium chloride (1.56 mL, 3.08 mmol, 2 M in tetrahydrofuran) was slowly and drop wise added to N-[(3-bromophenyl)(2-cyanophenyl)methylene]-2-methylpropane-2-sulfinamide (Scheme #5, N) (1.00 g, 2.57 mmol) in dry tetrahydrofuran (15 mL) at room temperature under argon atmosphere. The reaction was heated to 30° C. and stirred for 3 h and then cooled to 0° C. The reaction was quenched with water (5 mL) and extracted twice with ethyl acetate. The organic phases were pooled and washed with saturated aqueous ammonium chloride. The product was extracted five times with 2 M hydrochloric acid and once with 6 M hydrochloric acid. The water phase was neutralized with sodium hydroxide and extracted twice with ethyl acetate. The organic phase was concentrated. Column chromatography using 20-100% chloroform saturated with ammonia in chloroform and 0-100% chloroform saturated with ammonia in chloroform did not yield the pure product. Further purification was made by preparative HPLC using 5-100% acetonitrile in 0.1 M ammonium acetate/water followed by preparative HPLC (Column: Gemini C8) using acetonitrile:water 37:63+1% trifluoroacetic acid. The residue was partitioned between ethyl acetate and sodium bicarbonate. The organic phase was washed (water), dried over magnesium sulfate and concentrated. The residue was dissolved in hydrochloric acid in diethyl ether (0.13 mL, 1 M), stirred for 1 h at ambient temperature and then concentrated to give 30.1 mg (3.2% yield) of the title compound: 1H NMR (DMSO-d6) δ 8.27 (d, J=8.03 Hz, 1 H), 7.92 (d, J=7.78 Hz, 1 H), 7.84-7.76 (m, 2 H), 7.70 (d, J=8.03 Hz, 1 H), 7.64 (t, J=7.53 Hz, 1 H), 7.57-7.52 (m, 1 H), 7.39 (t, J=7.91 Hz, 1 H), 3.17-3.07 (m, 1 H), 0.88 (d, J=7.03 Hz, 3 H), 0.51 (d, J=6.78 Hz, 3 H); MS (ES) m/z 329, 331 [M+1]+.

Provenance & Evidence