反应详情

Treat a stirred solution of 5-methyltetrazole (0.38 g, 4.52 mmol, obtained from TCI US) and dimethylformamide (7 mL) at 0° C. portionwise with sodium hydride (0.19 g, 4.75 mmol, 60% dispersion in oil). Allow to warm to room temperature over one hour and add a solution of 1-(t-butoxycarbonyl)-4-(1-(2-methanesulfonyloxyethyl)-1H-benzimidazol-2-yl)-[1,4]diazepane (0.1.33 g, 3.03 mmol, Preparation 28) and dimethylformamide (7 mL). Heat at 100° C. for 6 hours. Cool, add ethyl acetate (50 mL) and wash with saturated NaHCO3 (3×25 mL) and brine (3×50 mL). Dry (MgSO4) the organic phase, filter and concentrate in vacuo. Purify the residue by chromatography (silica gel, 3.5×50 cm) eluting with ethyl acetate:hexane (1:1) to afford 4-{1-[2-(5-methyl-tetrazol-1-yl}-ethyl]-1H-benzoimidazol-2-yl}-[1,4]diazepane-1-carboxylic acid tert-butyl ester (0.45 g), Rf=0.21 (silica gel, methanol:dichloromethane, 1:1).

1. temperatureHeat at 100° C. for 6 hours
2. temperatureCool
3. washwash with saturated NaHCO3 (3×25 mL) and brine (3×50 mL)
4. dry with materialDry (MgSO4) the organic phase
5. filtrationfilter
6. concentrationconcentrate in vacuo
7. customPurify the residue by chromatography (silica gel, 3.5×50 cm)
8. washeluting with ethyl acetate:hexane (1:1)