1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 91531190, compound

Participants

Reaction Steps

A solution of tert-butyl (2-mercapto-benzoimidazol-1-yl)-acetate (Intermediate 3-I, 502 mg, 1.9 mmol) and DBU (289 mg, 284 μl, 1.9 mmol) in THF (1 ml) is added onto a solution of (3-bromo-propyl)-carbamic acid tert-butyl ester (407 mg, 1.71 mmol) in THF (1 ml). The resulting solution is stirred at rt for 2 h. It becomes slowly turbid and the undesired solid is filtered on a fritted funnel. The solution is diluted with THF (2 ml) and DIPEA (491 mg, 650 μl, 3.8 mmol) is added. The mixture is poured onto a suspension of 2-chlorotrityl chloride resin (200-400 mesh), 1% DVB (1.0-1.6 mmol/g, 475 mg, 0.76 mmol) in THF (1 ml) and allowed to stir for 3 h. The resin is filtered and rinsed with THF. The solvent is removed in vacuo and the residue diluted with dichloromethane (5 ml). This organic phase is washed with an aqueous citric acid solution (pH=4) and with water. The solvent is evaporated under reduced pressure. The same purification process is repeated using dichloromethane instead of THF as the solvent. The obtained organic phase is washed with a saturated aqueous KH2PO4 solution and water. Evaporation of the solvent in vacuo affords a residue that is purified by flash chromatography on silica-gel (AcOEt/heptane, 1:2), yielding the title compound (587 mg) in 73% as a colourless oil: tR=2.41 min (LC-2), ESI-MS (pos.): m/z 422.50 [M+H]+; 1H-NMR (CDCl3): δ (ppm) 1.37 (s, 9H, tBu), 1.39 (s, 9H, tBu), 1.74 (quint. 2H, CH2CH2N), 3.20 (dd, 2H), 3.38 (t, 2H), 4.67 (s, 2H, CH2CO2), 5.82 (br. s, 1H, NH), 7.10-7.29 (m, 3Harom), 7.65 (m, 1Harom).

Provenance & Evidence