3-(Bromomethyl)-1H-indazole, N1-BOC protected → HCID 67700777, compound

Participants

Reaction Steps

To a stirring solution of 597.8 mg (1.3 mmol) 2-(2,4-Dioxo-5-pyridin-3-yl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl)-acetamide, prepared as in Intermediate 48, in 15 mL DMF at 0° C. is added 3.13 mL (1.57 mmol, 1.2 equiv) of a 0.5M solution of KN(TMS)2 in toluene. The reaction is allowed to warm to RT over 20 min, then is cooled back to 0° C., and 445.4 mg (1.43 mmol, 1.1 equiv) of 3-bromomethyl-1-tert-butoxycarbonyl-1H-indazole is added in one portion. The reaction is allowed to warm to RT., and after 20 min is concentrated in vacuo. The residue is taken up in water-ethyl acetate, and is poured into a separatory funnel containing water and ethyl acetate. The layers were separated, and the aqueous layer is extracted with ethyl acetate. The combined organics were dried (Na2SO4) filtered and concentrated in vacuo to afford an amber oil, which is purified by silica gel flash column chromatography to afford 561 mg of the title compound as a viscous, glassy oil: 1H NMR (CDCl3, 400 MHz) δ8.52 (d, br, 2H, J=18.8), 8.01 (d, 1H, J=8.4), 7.78 (m, 2H), 7.46 (t, 1H, J=20), 7.36-7.23 (m, 6H), 7.13 (m, 2H), 6.93 (m, 2H), 4.95 (m, 1H), 4.41 (d, br, 1H), 4.34 (dd, 1H, J=5.2, 8.4), 3.83 (s, 3H), 3.83 (dd, 1H), 3.55 (dd, 1H, J=5.1, 16.6), 1.64 (s, 9H), 1.03 (dd, 6H, J=2.0, 6.5); low resolution MS (FAB)m/e 689 (MH+).

Provenance & Evidence