Methyl iodide → N-Isopropyl-2-[3-methyl-2,4-dioxo-5-phenyl-3-(3-phenyl-allyl)-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-phenyl acetamide

Participants

Reaction Steps

To a stirring solution of 200 mg (0.37 mmol) of 2-[2,4-Dioxo-5-phenyl-3-(3-phenyl-allyl)-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-phenyl acetamide, prepared as in Intermediate 41, in 3 mL of DMF at 0° C. is added 16 mg (0.41 mmol, 1.1 equiv) of sodium hydride (60% dispersion in mineral oil). The resulting solution is stirred 5 min, then 25 mL (0.41 mmol, 1.1 equiv) of methyl iodide is added. The reaction mixture is stirred 30 min at 0° C. then 19 h at RT and quenched with 1 mL H2O. The reaction mixture is diluted with 40 mL EtOAc and washed with 40 mL H2O. The organic layer is dried (MgSO4) and the solvents removed in vacuo. Purification of the resulting oil via reverse phase MPLC using a C-18 column and 70% acetonitrile/30% H2O with 0.1% TFA as eluent followed by lyophilization afforded 107 mg of the title compound as a white amorphous solid: 1H NMR (CDCl3, 300 MHz) δ7.53-7.05 (m, 18H), 6.79 (m, 1H), 6.15 (m, 1H), 5.97 (d, 1H, J=15.7), 5.09 (m, 1H), 4.44 (d, 1H, J=16.4), 3.95 (d, 1H, J=16.4), 3.07 (m, 2H), 2.28 (d, 1H, J=7.1), 1.61 (s, 3H), 1.14 (m, 6H); low resolution MS (FAB)m/e 558 (MH+), 423, 223.

Provenance & Evidence