Cesium carbonate → tert-butyl 8-(4-(4-chlorophenethyl)-2-oxopiperazin-1-yl)-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate

Participants

Reaction Conditions

Reaction Steps

A suspension of 4-(4-chlorophenethyl)piperazin-2-one (90 mg, 0.38 mmol), tert-butyl 8-bromo-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate (130 mg, 0.344 mmol), Cs2CO3 (123 mg, 0.378 mmol), CuI (131 mg, 0.688 mmol) and trans-1,2-bis(methylamino)cyclohexane (24 mg, 0.17 mmol) in dioxane (10 mL) was degassed by bubbling N2 through the suspension for 45 min. The suspension was put under N2 and heated at reflux for 5 d. The suspension was cooled, 9:0.9:0.1 CH2Cl2/MeOH/NH4OH (10 mL) was added, and the resulting suspension was stirred at 25° C. for 30 min. The suspension was passed through a plug of silica gel, and the filtrate was washed with brine. Activated carbon was added to the resulting solution, and the resulting suspension was filtered. The filtrate was dried over Na2SO4 and concentrated under reduced pressure. Flash chromatography on silica gel (Et2O/(8:1.9:0.1 Et2O/MeOH/NH4OH) afforded tert-butyl 8-(4-(4-chlorophenethyl)-2-oxopiperazin-1-yl)-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate as a tan solid. 2 N HCl in Et2O (100 mL) was added to a solution of the tan solid in CH2Cl2 (5 mL) under N2, and the resulting suspension was stirred at 25° C. for 16 h. The suspension was concentrated, and the resulting residue was dissolved in MeOH (1 mL). Et2O (100 mL) was added, the resulting suspension was filtered, and the solid was washed with Et2O and put in a vacuum oven at 40° C. for 1 h to afford 22 mg (13%) of the title compound as a tan solid: 1H NMR (500 MHz, DMSO-d6) δ 11.54 (br s, 1H), 9.16 (br s, 2H), 7.54-7.32 (m, 6H), 6.96 (d, J=8.0 Hz, 1H), 4.21-3.44 (m, 9H), 3.42-3.05 (m, 12H); ESI MS m/z 437 [M+H]+.

Provenance & Evidence