Quinuclidine, 3-amino-, dihydrochloride → 1-(1-Azabicyclo[2.2.2]oct-3-yl)-3-(5-phenyl-1,3-thiazol-4-yl) urea hydrochloride

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Reaction Steps

To a solution of 5-phenyl-1,3-thiazole-4-carboxylic acid (300 mg) in toluene (6 mL) were added dropwise TEA (672 μL) and DPPA (409 μL) at room temperature, followed by stirring at the same temperature for 20 minutes. Next, after stirring at 90° C. for 5 minutes, a mixture of 3-aminoquinuclidine dihydrochloride (407 mg) and DMF (2 mL) was added thereto, followed by heating under reflux for 1 hour. To the reaction liquid was added water, followed by extraction with EtOAc. The organic layer was washed with water and brine in this order, dried over MgSO4, and then concentrated under reduced pressure. The residue was purified by medium-pressure preparative liquid chromatography (YAMAZEN YFLC WPrep2XY, eluent; CHCl3:MeOH:28% aqueous ammonia=80:10:1) to obtain an oily substance. This was dissolved in EtOH, followed by addition of 10% HCl/MeOH at room temperature and concentration under reduced pressure. The residue obtained was added with EtOH and EtOAc, and left to stand, and the solid precipitated was collected by filtration, and washed with EtOAc to obtain 1-(1-azabicyclo[2.2.2]oct-3-yl)-3-(5-phenyl-1,3-thiazol-4-yl) urea hydrochloride (15 mg) as a white solid.

Provenance & Evidence