反应详情

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.

1. stirringNext, after stirring at 90° C. for 5 minutes
2. additionwas added
3. temperatureby heating
4. temperatureunder reflux for 1 hour
5. customTo the reaction liquid
6. extractionfollowed by extraction with EtOAc
7. washThe organic layer was washed with water and brine in this order
8. dry with materialdried over MgSO4
9. concentrationconcentrated under reduced pressure
10. customThe residue was purified by medium-pressure preparative liquid chromatography (YAMAZEN YFLC WPrep2XY, eluent; CHCl3:MeOH:28% aqueous ammonia=80:10:1)
11. customto obtain an oily substance
12. concentrationconcentration under reduced pressure
13. customThe residue obtained
14. waitleft
15. customthe solid precipitated
16. filtrationwas collected by filtration
17. washwashed with EtOAc