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

Participants

Reaction Conditions

Reaction Steps

To a stirring solution of 165 mg (0.27 mmol) of N-Isopropyl-N-(4-methoxy-phenyl)-2-[3-(1-methyl-1H-indazol-3-ylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]acetamide, prepared as in Example 49, in 5 mL of DMF at 0° C. is added 0.82 mL (0.82 mmol, 3.0 equiv) of a 1.0M solution of NaN(TMS)2 in THF. The resulting solution is stirred 5 min, and 51 μL (0.82 mmol, 3.0 equiv) of methyl iodide is added. The resulting solution is stirred for 4 h at RT, warmed to 50° C. for 16 h, and then quenched with 5 mL of H2O. The reaction mixture is poured into 50 mL of Et2O and extracted with H2O (2×50 mL). The organic layer is separated, dried (MgSO4), and the solvents removed in vacuo. Purification by silica gel MPLC on an Si60 column using hexane/EtOAc 4/3 as eluent followed by lyophilization in acetonitrile/H2O afforded 124 mg of the title compound as a white amorphous solid: 1H NMR (DMSO-d6, 300 MHz) δ7.48-6.95 (m, 16H), 6.71 (d, 1H, J=7.3), 4.78 (m, 1H), 4.21 (s, br, 2H), 3.95 (s, 3H), 3.74 (s, 3H), 2.79 (d, 2H, J=5.9), 1.20 (s, 3H), 0.93 (m, 6H); low resolution MS (FAB)m/e 616 (MH+).

Provenance & Evidence