反応 #5476

反応方程式

Sodium methoxide methanol

thionyl chloride

1-azabicyclo[3.3.1]nonane-5-methanamine

triethylamine

indole-3-carboxylic acid

→

title compound

収率 57.2%

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

収率 57.2%

溶媒

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

反応条件

後処理

1. 1
   温度the solution was refluxed for one hour
2. 2
   濃縮concentrated in vacuo
3. 3
   workup.ADDITIONwas treated with a solution of the
4. 4
   温度cooled (0° C.)
5. 5
   workup.STIRRINGthe solution was stirred for one hour
6. 6
   濃縮The filtrate was concentrated in vacuo
7. 7
   ろ過filtered
8. 8
   workup.ADDITIONEther was added dropwise to the filtrate until no more precipitation
9. 9
   温度the suspension was cooled (0° C.)
10. 10
    ろ過filtered
11. 11
    その他the solid was collected
12. 12
    その他dried in vacuo

実験手順

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.

出典