反应详情

温度

100 °C

Vinylboronic acid pinacol ester (2.4 ml) was added to 1-(5-bromopyridin-2-yl)-5-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (3.1 g) described in Reference Example 24(2), palladium (II) acetate (224 mg), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (S-Phos) (410 mg), tripotassium phosphate (5.3 g) and tetrahydrofuran (20 ml), and stirred at 100° C. for 6.5 hours. Then palladium (II) acetate (22.4 mg), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (S-Phos) (41 mg), vinylboronic acid pinacol ester (240 μl) and tripotassium phosphate (530 mg) were added therein, and stirred at 100° C. for 8.5 hours. Water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate). 1,4-Dioxane (28 ml) and 10% palladium-carbon (containing ca. 50% of water; 700 mg) were added to the purified yellow oily product and the mixture was stirred under hydrogen atmosphere at room temperature for 6 hours. The reaction solution was filtered through Celite, concentrated in vacuo and the residue was purified with silica gel column chromatography (n-hexane/ethyl acetate). 4N Aqueous solution of sodium hydroxide (5 ml), water (5 ml) and ethanol (10 ml) were added to the purified oily product and the mixture was stirred at 80° C. for 4.5 hours. The reaction solution was concentrated in vacuo and 1N hydrochloric acid aqueous solution was added to the residue at 0° C. and then the precipitated solid was washed with water to give the titled compound (1.16 g) as a gray solid.

1. stirringstirred at 100° C. for 8.5 hours
2. extractionthe mixture was extracted with ethyl acetate
3. washThe organic layer was washed with water and saturated brine
4. dry with materialdried over anhydrous sodium sulfate
5. concentrationconcentrated in vacuo
6. customThe resulting residue was purified with silica gel column chromatography (n-hexane/ethyl acetate)
7. addition1,4-Dioxane (28 ml) and 10% palladium-carbon (containing ca. 50% of water; 700 mg) were added to the purified yellow oily product
8. stirringthe mixture was stirred under hydrogen atmosphere at room temperature for 6 hours
9. filtrationThe reaction solution was filtered through Celite
10. concentrationconcentrated in vacuo
11. customthe residue was purified with silica gel column chromatography (n-hexane/ethyl acetate)
12. addition4N Aqueous solution of sodium hydroxide (5 ml), water (5 ml) and ethanol (10 ml) were added to the purified oily product
13. stirringthe mixture was stirred at 80° C. for 4.5 hours
14. concentrationThe reaction solution was concentrated in vacuo and 1N hydrochloric acid aqueous solution
15. additionwas added to the residue at 0° C.
16. washthe precipitated solid was washed with water