反应详情

温度

60 °C

To a solution of 4′-{[4-(1,4-dioxaspiro[4.5]dec-8-yl)-5-oxo-7-propyl-4,5-dihydropyrazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile (27.7 g) in tetrahydrofuran (200 mL) was added 3M hydrochloric acid (200 mL), and the mixture was stirred at 60° C. for 15 hr. The mixture was allowed to cool to room temperature, diluted with ethyl acetate, and neutralized with 8M aqueous sodium hydroxide solution. The mixture was extracted with ethyl acetate, and the organic layer was successively washed with water and brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was crystallized using ethyl acetate, and the resulting solid was collected by filtration, and dissolved in tetrahydrofuran (100 mL). This solution was added dropwise to a solution of lithium borohydride (2M tetrahydrofuran solution, 37 mL) in tetrahydrofuran (150 mL) at −5° C. over 30 min. After stirring for 1.5 hr, ethyl acetate and saturated aqueous ammonium chloride solution were added. The mixture was extracted with ethyl acetate, and the organic layer was successively washed with water and brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography to give the title compound as a pale-yellow amorphous solid (21.1 g, 83%).

1. temperatureto cool to room temperature
2. extractionThe mixture was extracted with ethyl acetate
3. washthe organic layer was successively washed with water and brine
4. dry with materialdried over anhydrous magnesium sulfate
5. concentrationconcentrated
6. customThe residue was crystallized
7. filtrationthe resulting solid was collected by filtration
8. dissolutiondissolved in tetrahydrofuran (100 mL)
9. additionThis solution was added dropwise to a solution of lithium borohydride (2M tetrahydrofuran solution, 37 mL) in tetrahydrofuran (150 mL) at −5° C. over 30 min
10. stirringAfter stirring for 1.5 hr
11. additionethyl acetate and saturated aqueous ammonium chloride solution were added
12. extractionThe mixture was extracted with ethyl acetate
13. washthe organic layer was successively washed with water and brine
14. dry with materialdried over anhydrous magnesium sulfate
15. concentrationconcentrated
16. customThe residue was purified by silica gel column chromatography