反应 #43763

反应方程式

7-nitro-1-benzothiophene-2-carboxylic acid

EDC

HOBt

triethylamine

→

title compound

N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-7-nitro-1-benzothiophene-2-carboxamide hydrochloride

溶剂

DMF

反应条件

后处理

1. 1
   其他The reaction is terminated by addition of a 10% strength aqueous sodium bicarbonate solution, and ethyl acetate
2. 2
   workup.ADDITIONis added
3. 3
   过滤The resulting precipitate is filtered off with suction
4. 4
   萃取The mother liquor is extracted twice with ethyl acetate
5. 5
   浓缩concentrated
6. 6
   其他Both the precipitate and the concentrated mother liquor are purified by silica gel column chromatography (mobile phase: dichloromethane/methanol/25% ammonia 100:10:2)
7. 7
   浓缩The product fractions are concentrated
8. 8
   workup.DISSOLUTIONdissolved in a mixture of methanol and 1N hydrochloric acid
9. 9
   浓缩again concentrated
10. 10
    其他dried under high vacuum
11. 11
    其他The resulting solid is triturated with acetonitrile
12. 12
    过滤filtered off with suction
13. 13
    其他dried at 50° C. under reduced pressure

实验过程

2.0 g (8.96 mmol) of 7-nitro-1-benzothiophene-2-carboxylic acid and 1.78 g (8.96 mmol) of R-3-aminoquinuclidine dihydrochloride are initially charged in 25 ml of DMF. At 0° C., 2.06 g (10.75 mmol) of EDC, 1.45 g (10.75 mmol) of HOBt and 4.50 ml (32.26 mmol) of triethylamine are added to the solution. The mixture is stirred at RT for 18 h. The reaction is terminated by addition of a 10% strength aqueous sodium bicarbonate solution, and ethyl acetate is added. The resulting precipitate is filtered off with suction. The mother liquor is extracted twice with ethyl acetate. The organic phases are combined and concentrated. Both the precipitate and the concentrated mother liquor are purified by silica gel column chromatography (mobile phase: dichloromethane/methanol/25% ammonia 100:10:2). The product fractions are concentrated, dissolved in a mixture of methanol and 1N hydrochloric acid, then again concentrated and dried under high vacuum. The resulting solid is triturated with acetonitrile, filtered off with suction and dried at 50° C. under reduced pressure. 1.10 g (32.8% of theory) of the title compound are obtained.

来源