反应详情

A solution of 1-methyl-1H-indole-3-carboxylic acid (1.53 g, 8.7 mmol) in anhydrous tetrahydrofuran (8 mL) under nitrogen was treated with 1.49 g (9.2 mmol) of 1,1'-carbonyldiimidazole (CDI) and stirred for 10 minutes. At this point a thick suspension formed, and anhydrous N,N-dimethylformamide (8 mL) was added. After an additional 45 minutes the solution was degassed under a stream of nitrogen over 10 minutes, then treated with a solution of 1-azabicyclo[3.3.1]nonane-5-methanamine (1.47 g, 9.5 mmol). After 18 hours at room temperature and six hours at 55°-60° C., no acid-CDI adduct was detected by TLC (5% methanol/methylene chloride on alumina), and the mixture was concentrated in vacuo. The residue was partitioned between 3N sodium hydroxide (50 mL) and toluene (100 mL) containing a little 2-propanol. The organic layer as separated and the aqueous solution was extracted with toluene (50 mL) containing some 2 -propanol. The combined organic solution was dried (Na2SO4), concentrated in vacuo, and the residue filtered through alumina (eluted with 20% methanol/tetrahydrofuran). The filtrate was concentrated in vacuo and the residue triturated from ether/petroleum ethers (30°-60° ) to give a solid, which was recrystallized from tetrahydrofuran/hexane to afford 2.06 g (76%) of colorless crystals; mp 145°-147° C.

1. customAt this point a thick suspension formed
2. customAfter an additional 45 minutes the solution was degassed under a stream of nitrogen over 10 minutes
3. waitAfter 18 hours at room temperature
4. customsix hours
5. customat 55°-60° C.
6. concentrationthe mixture was concentrated in vacuo
7. customThe residue was partitioned between 3N sodium hydroxide (50 mL) and toluene (100 mL)
8. additioncontaining a little 2-propanol
9. customThe organic layer as separated
10. extractionthe aqueous solution was extracted with toluene (50 mL)
11. additioncontaining some 2 -propanol
12. dry with materialThe combined organic solution was dried (Na2SO4)
13. concentrationconcentrated in vacuo
14. filtrationthe residue filtered through alumina (eluted with 20% methanol/tetrahydrofuran)
15. concentrationThe filtrate was concentrated in vacuo
16. customthe residue triturated from ether/petroleum ethers (30°-60° )
17. customto give a solid, which
18. customwas recrystallized from tetrahydrofuran/hexane