반응 #5476

반응 방정식

Sodium methoxide methanol

thionyl chloride

1-azabicyclo[3.3.1]nonane-5-methanamine

triethylamine

indole-3-carboxylic acid

→

title compound

수율 57.2%

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

수율 57.2%

용매

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

반응 조건

후처리

1. 1
   온도the solution was refluxed for one hour
2. 2
   농축concentrated in vacuo
3. 3
   workup.ADDITIONwas treated with a solution of the
4. 4
   온도cooled (0° C.)
5. 5
   workup.STIRRINGthe solution was stirred for one hour
6. 6
   농축The filtrate was concentrated in vacuo
7. 7
   여과filtered
8. 8
   workup.ADDITIONEther was added dropwise to the filtrate until no more precipitation
9. 9
   온도the suspension was cooled (0° C.)
10. 10
    여과filtered
11. 11
    기타the solid was collected
12. 12
    기타dried in vacuo

실험 절차

A cooled (0° C.) suspension/solution of indole-3-carboxylic acid (0.92 g, 5.7 mmol) in anhydrous tetrahydrofuran (10 mL) was treated dropwise with thionyl chloride (0.72 g, 6.0 mmol), and the solution was refluxed for one hour and concentrated in vacuo. A cooled (0° C.) solution of 1-azabicyclo[3.3.1]nonane-5-methanamine (0.96 g, 6.2 mmol) and triethylamine (1.22 g, 12 mmol) in anhydrous tetrahydrofuran (5 mL) was treated with a solution of the above prepared acid chloride in anhydrous tetrahydrofuran (10 mL), and the mixture was stirred at room temperature for 15 hours, at 55° C. for one hour, and cooled (0° C.). Sodium methoxide/methanol (25%, 2.6 g, 12 mmol) was added, and the solution was stirred for one hour and passed through a column of alumina (eluted with 1:1 methanol/tetrahydrofuran). The filtrate was concentrated in vacuo and taken up in 2-propanol and filtered. Ether was added dropwise to the filtrate until no more precipitation was observed, and the suspension was cooled (0° C.), filtered, and the solid was collected and dried in vacuo to afford (after a second crop) 0.97 g (57%) of the title compound as a colorless solid; mp 139.0°-141.5° C.

출처