Dimethyl Sulfoxide → 6-[(4-tert-Butylphenyl)sulfonyl]-7-methyl-8-(methylsulfonyl)-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine

Participants

Reaction Conditions

Reaction Steps

A mixture of 8-bromo-6-[(4-tert-butylphenyl)sulfonyl]-7-methyl-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine (intermediate 63, 100 mg, 0.180 mmol) sodium methyl sulfinate (55.2 mg, 0.541 mmol) and copper (II) triflate benzene complex (27.2 mg, 0.054 mmol) was flushed with nitrogen and capped, and was added N,N′-dimethyl ethylenediamine (0.12 mL, 0.108 mmol), and DMSO (0.60 mL). The mixture was heated to 110° C. for 36 h. After cooling to rt, the reaction mixture was diluted with EtOAc, filtered through silica gel, the filtrated was washed with water and brine, and concentrated. The residue was purified by reverse phase HPLC to provide the title compound as a racemic mixture. LC/MS: m/e 553.9 (M+H)+; 1H NMR (500 MHz, CD3OD): δ 7.87 (1H, d), 7.63 (1H, d), 7.19 (2H, d), 7.13 (1H, d), 7.07 (1H, d), 7.02 (2H, d), 5.21 (1H, d), 4.45 (1H, d), 3.15 (3H, s), 2.87 (3H, s), 1.23 (9H, s). The racemic mixture was separated on a Chiracel OD-H column eluting with 20% EtOH in hexanes, at 8.0 mL/min. The faster eluting enantiomer E1 has a retention time of 15.7 min. The slower eluting enantiomer E2 has a retention time of 28.5 min.

Provenance & Evidence