Benzenamine, 4-(4-morpholinyl)- → 2-Butyl-5-(3-chlorophenyl)-4-[(4-morpholin-4-ylphenyl)amino]isothiazol-3(2H)-one 1,1-dioxide

Participants

Reaction Conditions

Reaction Steps

4-Morpholin-4-ylaniline (53 mg, 0.30 mmol) was added to a solution of 2-butyl-4-chloro-5-(3-chlorophenyl)isothiazol-3(2H)-one 1,1-dioxide (50 mg, 0.15 mmol) in dry DMF (1.0 mL) at rt and under an atmosphere of nitrogen. The reaction mixture was heated in a microwave reactor at 140° C. for 25 mins, whereafter the solvents were removed. Another portion of 4-morpholin-4-ylaniline (160 mg, 0.90 mmol) was added to a solution of 2-butyl-4-chloro-5-(3-chlorophenyl)isothiazol-3(2H)-one 1,1-dioxide (150 mg, 0.45 mmol) in dry DMF (2.0 mL) at rt and under an atmosphere of nitrogen. The reaction mixture was heated in a microwave reactor at 140° C. for 25 mins, whereafter the solvents were removed. The obtained two mixtures were combined and purified using preparative HPLC (column ACE C8, 0.1M NH4OAc/MeCN, gradient) followed by column chromatography (Horizons Biotage, Heptane:EtOAc, 3:1, isocratic run) to give the title compound (132 mg, 62%) as a yellow solid; 1H NMR (500 MHz, CDCl3): δ 7.22 (bs, 1H), 7.13-7.19 (m, 2H), 7.06-7.11 (m, 1H), 6.93-6.96 (m, 1H), 6.65-6.69 (m, 2H), 6.55-6.60 (m, 2H), 3.82-3.86 (m, 4H), 3.75-3.80 (t, 2H), 3.04-3.08 (m, 4H), 1.83-1.91 (m, 2H), 1.44-1.52 (m, 2H), 1.01 (t, 3H); 13C NMR (125 MHz, CDCl3): δ 159.3, 149.8, 134.2, 132.6, 130.3, 129.3, 129.0, 127.9, 127.3, 126.8, 124.3, 115.6, 107.8, 66.9, 49.6, 40.5, 30.4, 20.3, 13.8; Mass Spectrum: M−H 474.

Provenance & Evidence