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

Participants

Reaction Conditions

Reaction Steps

To a stirring solution of 200 mg (0.30 mmol) of 2-[3-(1-Benzyl-1H-indazol-3-ylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-(4-methoxy-phenyl) acetamide in 5 mL of DMF is added 0.45 mL (0.45 mmol, 1.5 equiv) of a 1.0M solution of NaN(TMS)2. The resulting solution is stirred 5 min, then 76 mg (0.54 mmol, 1.8 equiv) of methyl iodide is added. The resulting solution is stirred at RT for 1 h then heated to 50° C. for 16 h. The solution is cooled to RT, poured into 40 mL of EtOAc and extracted with H2O (1×40 mL), dried (MgSO4), and the solvent removed in vacuo. Purification of the resulting material by silica gel flash chromatography with hexane/ethyl acetate 3/2 as eluent gave 127 mg of the title compound as an off-white solid, contaminated with starting material, which is inseparable, in a ratio of approximately 1/1: 1H NMR (300 MHz, CDCl3) δ7.86 (d, 1H, J=8.1), 7.33-6.88 (m, 21H), 5.58 (s, 2H), 5.43 (s, 2H), 5.05 (m, 1H), 5.00 (m, 1H), 4.50 (d, 1H), 4.25 (m, 3H), 3.85 (s, 3H), 3.58 (dd, 1H, J=5.1, 16.0), 1. 59 (s, 3H), 1.06 (2×d, 6H, J=6.6); Rf =0.15 in hexane/ethyl acetate 2/1.

Provenance & Evidence