反应详情

温度

100 °C

A mixture of tert-butyl [2-isobutyl-4-(4-methylphenyl)-6-trifluoromethanesulfonyloxy-quinolin-3-yl]methylcarbamate (0.50 g, 0.90 mmol), boron bispinacolate (0.25 g, 1.0 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium-dichloromethane (1:1) complex (0.020 g, 0.027 mmol), potassium acetate (0.27 g, 2.7 mmol) and dimethyl sulfoxide (20 ml) was stirred under an argon atmosphere at 100° C. for 15 min. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and a mixture of the residue, 2-chlorothiazole (0.17 g, 0.90 mmol), tetrakis(triphenylphosphine)palladium (0.10 g, 0.090 mmol), potassium carbonate (0.63 g, 4.5 mmol), ethanol (4 ml), toluene (20 ml) and water (4 ml) was stirred under an argon atmosphere at 100° C. for 17 hrs. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography. The obtained mixture was dissolved in tetrahydrofuran-methanol (1:1, 8 ml) and 1N aqueous sodium hydroxide solution (2 ml) was added. The mixture was stirred at room temperature for 15 min. 1N Hydrochloric acid (50 ml) was added to the reaction mixture and the mixture was extracted with ethyl acetate-tetrahydrofuran (1:1, 100 ml). The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give 2-[3-{[(tert-butoxycarbonyl)amino]methyl}-2-isobutyl-4-(4-methylphenyl)quinolin-6-yl]-1,3-thiazole-4-carboxylic acid (0.17 g, yield 36%) as pale-yellow crystals.

1. extractionextracted with ethyl acetate
2. washThe extract was washed with saturated brine
3. dry with materialdried over anhydrous magnesium sulfate
4. customThe solvent was evaporated under reduced pressure
5. stirringwas stirred under an argon atmosphere at 100° C. for 17 hrs
6. extractionextracted with ethyl acetate
7. washThe extract was washed with saturated brine
8. dry with materialdried over anhydrous magnesium sulfate
9. customThe solvent was evaporated under reduced pressure
10. customthe residue was purified by silica gel column chromatography
11. dissolutionThe obtained mixture was dissolved in tetrahydrofuran-methanol (1:1, 8 ml)
12. addition1N aqueous sodium hydroxide solution (2 ml) was added
13. stirringThe mixture was stirred at room temperature for 15 min
14. addition1N Hydrochloric acid (50 ml) was added to the reaction mixture
15. extractionthe mixture was extracted with ethyl acetate-tetrahydrofuran (1:1, 100 ml)
16. washThe extract was washed with saturated brine
17. dry with materialdried over anhydrous magnesium sulfate
18. customThe solvent was evaporated under reduced pressure
19. customthe residue was purified by silica gel column chromatography