반응 #5477

반응 방정식

1-azabicyclo[3.3.1]nonane-5-methanamine

1-methyl-1H-indole-3-carboxylic acid

1,1'-carbonyldiimidazole

N,N-dimethylformamide

→

colorless crystals

수율 79.6%

N-(1-Azabicyclo[3.3.1]non-5-ylmethyl)-1H-indole-3-carboxamide

수율 79.6%

용매

tetrahydrofuran

methanol methylene chloride

반응 조건

후처리

1. 1
   기타At this point a thick suspension formed
2. 2
   기타After an additional 45 minutes the solution was degassed under a stream of nitrogen over 10 minutes
3. 3
   workup.WAITAfter 18 hours at room temperature
4. 4
   기타six hours
5. 5
   기타at 55°-60° C.
6. 6
   농축the mixture was concentrated in vacuo
7. 7
   기타The residue was partitioned between 3N sodium hydroxide (50 mL) and toluene (100 mL)
8. 8
   workup.ADDITIONcontaining a little 2-propanol
9. 9
   기타The organic layer as separated
10. 10
    추출the aqueous solution was extracted with toluene (50 mL)
11. 11
    workup.ADDITIONcontaining some 2 -propanol
12. 12
    건조The combined organic solution was dried (Na2SO4)
13. 13
    농축concentrated in vacuo
14. 14
    여과the residue filtered through alumina (eluted with 20% methanol/tetrahydrofuran)
15. 15
    농축The filtrate was concentrated in vacuo
16. 16
    기타the residue triturated from ether/petroleum ethers (30°-60° )
17. 17
    기타to give a solid, which
18. 18
    기타was recrystallized from tetrahydrofuran/hexane

실험 절차

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.

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