反应详情

A cooled (0° C.) solution of 1-azabicyclo[3.2.1]oct-5-ylmethanol (1.70 g, 12 mmol) in anhydrous tetrahydrofuran (15 mL) under nitrogen was treated (via syringe) with 2.45N n-butyllithium/hexane (12 mmol), then stirred at room temperature for thirty minutes and concentrated in vacuo to remove all hexane. Anhydrous tetrahydrofuran (15 mL) was added, followed by 3-(3H-imidazol-1-ylcarbonyl)-1-methyl-1H-indazole (2.49 g, 11 mmol), and the mixture was stirred under nitrogen at room temperature for 18 hours, then at 60° C. for three hours, and concentrated in vacuo. The residue was partitioned between 1.0N sodium carbonate (75 mL) and toluene (125 mL) containing some 2-propanol, and the organic layer was set aside. The aqueous solution was extracted with toluene (2×50 mL) containing some 2-propanol, and the combined organic solution was rinsed with water to remove imidazole, then dried azeotropically with toluene. The residue was filtered through alumina (eluted with 15% methanol/tetrahydrofuran), concentrated in vacuo, and triturated from ether/petroleum ethers (30°-60°), then recrystallized from ether/petroleum ethers (30°-60°) to afford 1.75 g (53%) of the product as a colorless solid; mp 93°-95° C.

1. concentrationconcentrated in vacuo
2. customto remove all hexane
3. additionAnhydrous tetrahydrofuran (15 mL) was added
4. stirringthe mixture was stirred under nitrogen at room temperature for 18 hours
5. concentrationconcentrated in vacuo
6. customThe residue was partitioned between 1.0N sodium carbonate (75 mL) and toluene (125 mL)
7. additioncontaining some 2-propanol
8. extractionThe aqueous solution was extracted with toluene (2×50 mL)
9. additioncontaining some 2-propanol
10. washthe combined organic solution was rinsed with water
11. customto remove imidazole
12. dry with materialdried azeotropically with toluene
13. filtrationThe residue was filtered through alumina (eluted with 15% methanol/tetrahydrofuran)
14. concentrationconcentrated in vacuo
15. customtriturated from ether/petroleum ethers (30°-60°)
16. customrecrystallized from ether/petroleum ethers (30°-60°)