Hydrochloric Acid → 6-Iodo-1-[2-(trimethyl-silanyl)-ethoxymethyl]-3-{1-[2-(trimethyl-silanyl)-ethoxymethyl]-1H-benzoimidazol-2-yl}-1H-indazole

Participants

Reaction Conditions

Reaction Steps

A solution of 6-amino-1-[2-(trimethyl-silanyl)-ethoxymethyl]-3-{1-[2-(trimethyl-silanyl)-ethoxymethyl]-1-H-benzoimidazol-2-yl}-1-H-indazole (500 mg, 0.98 mmol) in acetic acid (1.5 mL) was diluted with H2O (1.0 mL) and stirred at 0° C. Concentrated HCl (250 μL, ˜3 mmol) in H2O (250 μL) was added. Sodium nitrate (90 mg, 1.3 mmol) in H2O (300 μL) was added, and the reaction stirred for 8 min. Iodine (10 mg) and a solution of potassium iodide (250 mg, 1.3 mmol) in H2O (250 μL) were added, and the frothing reaction stirred for 30 min at 23° C. The reaction was diluted with H2O (25 mL) and extracted with ethyl acetate (2×20 mL). Organics were washed with saturated sodium metabisulfite solution (10 mL) and brine (10 mL), dried (Na2SO4), and concentrated in vacuo. Purification by silica gel chromatography (8% ethyl acetate/hexanes) gave 316 mg (52%) of 6-iodo-1-[2-(trimethyl-silanyl)-ethoxymethyl]-3-{1-[2-(trimethyl-silanyl)-ethoxymethyl]-1-H-benzoimidazol-2-yl}-1-H-indazole as a faintly yellow oil, which slowly crystallized to a white solid. 1H NMR (300 MHz, CDCl3) δ 8.45 (d, 1H, J=9.0 Hz), 8.05 (s, 1H), 7.91-7.88 (m, 1H), 7.67-7.62 (m, 2H), 7.38-7.34 (m, 2H), 6.24 (s, 2H), 5.77 (s, 2H), 3.65-3.57 (m, 4H), 0.93 (t, 2H, J=8.1 Hz), 0.85 (t, 2H, J=8.1 Hz), −0.04 (s, 9H), −0.15 (s, 9H). Anal. (C26H37IN4O2Si2) C, H, N. Calculated: C, 50.31; H, 6.01; N, 9.03. Found: C, 50.55; H, 6.08; N, 9.00.

Provenance & Evidence