Sodium bis(trimethylsilyl)amide → HCID 67699907, compound

Participants

Reaction Steps

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 8 mL of DMF at 0° C. is added 0.78 mL (0.78 mmol, 1.2 equiv) of a 1.0M solution of NaN(TMS)2 in THF. The resulting solution is stirred 5 min, and a solution of 154 mg (0.972 mmol, 1.1 equiv.) of 3-bromomethyl isoxazolo[5,4-b]pyridine (Abignente, A.; De Capraris, P.; Stein, M. L. Farmaco Ed. Sci. 1975, 30, 992) in 2 mL of DMF is added. The resulting solution is stirred for 2.5 h at RT then quenched with 5 mL of H2O. The reaction mixture is poured into 50 mL of EtOAc 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 using an Si60 column and hexane/EtOAc 1/1 as eluent afforded 280 mg of the title compound as a white amorphous solid: 1H NMR (CDCl3, 400 MHz) δ8.57 (dd, 1H, J=1.5, 4.6), 8.23 (dd, 1H, J=1.5, 7.8), 7.39-7.10 (m, 12H), 6.94 (m, 2H), 4.99 (m, 1H), 4.23 (m, 3H), 3.84 (s, 3H), 3.79 (d 1H, J=8.4), 3.57 (dd, 1H, J=5.3, 16.4), 1.06 (d, 6H, J=6.8); low resolution MS (FAB)m/e 590 (MH+), 589 (M+), 425; Anal. (C34H31N5O5) Calcd. C, 69.26; H, 5.30; N, 11.88 Found C, 69.13; H, 5.32; N, 11.84.

Provenance & Evidence