1-(Bromomethyl)naphthalene → N-Isopropyl-N-(4-methoxy-phenyl)-2-(3-naphthalen-1-ylmethyl-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl) acetamide

関与物質

反応手順

To a stirring solution of 300 mg (0.66 mmol) of 2-(2,4-Dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl) acetamide, prepared as in Intermediate 4, in 10 mL DMF at 0° C. is added dropwise over 5 min 1.45 mL (0.72 mmol, 1.1 equiv) of a 0.5M solution of KN(TMS)2 in toluene. The resulting solution is stirred 10 min, then a solution of 160 mg (0.72 mmol, 1.1 equiv) of 1-bromomethylnaphthalene in 3 mL DMF is added. The resulting solution is stirred 2 h at RT and then quenched with 5 mL of H2O. The reaction mixture is then 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 of the material by silica gel MPLC on an Si60 column using hexane/EtOAc 2/1 as eluent followed by lyophilization in acetonitrile/H2O afforded 385 mg of the title compound as a white amorphous solid: 1H NMR (CDCl3, 300 MHz) δ8.01 (d, 1H, J=8.0), 7.80 (d, 1H, J=7.4), 7.69 (d, 1H, J=8.0), 7.50-6.94 (m, 16H), 6.84 (dd, 1H, J=1.5, 8.3), 5.04 (m, 1H), 4.36 (d, 1H, J=16.4), 4.17 (d, 1H, J=16.4), 3.92 (m, 2H), 3.85 (s, 3H), 3.82 (m, 1H), 1.09 (t, 6H, J=7.1); low resolution MS (FAB)m/e 598 (MH+), 597 (M+), 433.

情報源と証拠