反应详情

Combine 1-benzoyl-3-(3,4-dimethoxy-phenyl)-3-(2-methanesulfonyl-ethyl)-pyrrolidine (0.54 g, 1.3 mmol) and 4-[1-(4-fluoro-benzyl)-1 H-benzoimidazole-2-carbonyl]-piperidine (0.46 g, 1.4 mmol), and sodium bicarbonate (0.2 g, 2.5 mmol) in tetrahydrofuran/water (15/4) (30 mL). Heat to reflux. After 48 hours, cool to ambient temperature. After 72 hours, evaporate in vacuo to obtain a residue. Partition the residue between dichloromethane/chloroform and 5% sodium bicarbonate solution. Dry the organic layer over Na2SO4, filter, and concentrate in vacuo to obtain a residue. Chromatograph the residue on silica gel eluting with 5/1 ethyl acetate/methanol to give a solid. Combine the solid with dichloromethane and extract with 5% sodium bicarbonate solution. Dry the organic layer over Na2SO4, filter, and concentrate in vacuo to obtain a residue. Dry the residue in vacuo at 82° C. to give the title compound: Rf=0.28 (silica gel, 5/1 ethyl acetate/methanol); mp; 88-90° C. Elemental Analysis calculated for C41H43FN4O4: C 72.20; H 6.47; N 8.21; Found: C 71.96; H 6.38; N 8.17.

1. temperatureHeat to reflux
2. waitAfter 72 hours
3. customevaporate in vacuo
4. customto obtain a residue
5. customPartition the residue between dichloromethane/chloroform and 5% sodium bicarbonate solution
6. dry with materialDry the organic layer over Na2SO4
7. filtrationfilter
8. concentrationconcentrate in vacuo
9. customto obtain a residue
10. extractionextract with 5% sodium bicarbonate solution
11. dry with materialDry the organic layer over Na2SO4
12. filtrationfilter
13. concentrationconcentrate in vacuo
14. customto obtain a residue
15. customDry the residue in vacuo at 82° C.