3-(Bromomethyl)-1H-indazole, N1-BOC protected → HCID 86753595, compound

Participants

Reaction Steps

To a stirring solution of 260 mg (0.55 mmol) 2-[5-(3-Fluorophenyl)-2,4-dioxo-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-(4-methoxy-phenyl)-acetamide, prepared as in Part A, in 4 mL DMF at 0° C. is added 1.3 mL (0.66 mmol, 1.2 equiv) KN(TMS)2 via syringe under N2. The reaction is allowed to warm to RT, and is stirred at RT for 20 min. The reaction is cooled to 0° C., and 200 mg (0.66 mmol, 1.2 equiv) 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. The reaction is then transferred to 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. The residue is purified by silica gel flash column chromatography (gradient 3:1-2:1 hexanes:ethyl acetate) to afford 248 mg of the title compound as a pale yellow foam: 1H NMR (CDCl3, 400 MHz) δ8.03 (d, br, 1H, J=8.4), 7.84 (d, 1H, J=8.0), 7.46 (t, 1H, J=7.7), 7.38-7.11 (m, 6H), 6.99-6.93 (m, 3H), 4.97 (m, 1H), 4.19 (d, 1H, J=16.6), 3.83 (s, 3H), 3.83 (m, 1H) 3.52 (dd, 1H, J=4.8, 16.6), 1.64 (s, 9H), 1.04 (d, 6H, J=6.7); low resolution MS (FAB)m/e 706 (MH+).

Provenance & Evidence