Anisole → HCID 51030519, compound

Participants

Reaction Conditions

Reaction Steps

(S)-7-Chloro-3-(2-chlorobenzyl)-5-(3-(3-hydroxypropyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one was dissolved in dichloroethane (2 mL) and anisole (200 μL) was added followed by AlCl3 (165 mg). This mixture was heated to 85-90° C. for one hour. After cooling, the mixture was diluted with ethyl acetate and quenched with ice. 1M Citric acid was added and the layers separated. The organic layer was washed with brine, then dried (MgSO4). After filtration, the solvent was evaporated onto silica gel. Chromatography eluting with 5% ethyl acetate in hexanes for 5 min then a gradient over 30 minutes up to 100% ethyl acetate gave the crude product as a yellow foam (70 mg). The product was re-columned twice with DCM—10% MeOH in DCM to provide (S)-7-chloro-3-(2-chlorobenzyl)-5-(3-(3-hydroxypropyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)-1H-benzo[e][1,4]diazepin-2(3H)-one (20 mg) as a white solid that was 97% pure by HPLC: MP=210° C.; Optical rotation: C=1.0 (CHCl3), [α]D=−26°; MS (m/z): 509.6; 1H NMR (d6-DMSO) δ 11.5 (s, 1H), 10.7 (s, 1H), 7.6 (d, 1H) 7.5 (d, 1H), 7.4 (d, 1H), 7.3-7.2 (m, 4H), 7.1 (s, 1H), 6.95 (d, 1H), 6.85 (d, 1H), 4.3 (m, 2H), 3.8 (m, 2H), 3.7 (m, 1H), 3.5-3.3 (m, 2H), 2.1-2.0 (m, 2H).

Provenance & Evidence