反应详情

温度

0 °C

To a solution of 250 mg of 2-(2,4-Dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-trifluoromethoxy-phenyl) acetamide, prepared as in Part C, in 5 mL of dry DMF at 0° C. is added 1.5 mL of a 0.5M solution of potassium bis(trimethylsilyl)amide in toluene. The reaction mixture is stirred for 30 min at 0° C. and a solution of 170 mg of 3-Bromomethyl-6-fluoro-1-tert-butoxycarbonyl-indazole in 3 mL of dry DMF is added dropwise. The reaction mixture is stirred overnight at RT, poured into water and the product extracted with ethyl acetate (2×15 mL). The solvent is removed in vacuo and the residue is purified by silica gel flash column chromatography using hexane/EtOAc 1/1 as eluent to afford 100 mg of the title compound: 1H NMR (300 MHz, CDCl3) δ7.98-6.95 (m,16H) 5.07 (m, 1H), 4.30 (m, 3H), 3.86 (dd, 1H, J=16.5, 6.4), 3.65 (dd, 1H,J=16.5,6.4), 1.69 (s, 9H), 1.13 (d, 6H, J=6.8).

1. stirringThe reaction mixture is stirred overnight at RT
2. extractionthe product extracted with ethyl acetate (2×15 mL)
3. customThe solvent is removed in vacuo
4. customthe residue is purified by silica gel flash column chromatography