反应 #62029

反应方程式

N-((3R)-1-azabicyclo[2.2.2]oct-3-yl)-5-(bromo)benzo[d]isothiazole-3-carboxamide

caesium bicarbonate

(2′-dicyclohexylphosphanylbiphenyl-2-yl)dimethylamine

→

6-morpholin-4-ylbenzo[d]isothiazole-3-carboxylic acid ((3R)-1-azabicyclo[2.2.2]oct-3-yl)amide

收率 180.3%

反应条件

后处理

1. 1
   其他The vial was then evacuated
2. 2
   workup.ADDITIONback-filled with argon gas
3. 3
   workup.ADDITIONThe mixture of solids
4. 4
   workup.ADDITIONwas then diluted with morpholine (0.7 mL), dioxane (1 mL), and triethylamine (0.5 mL)
5. 5
   其他the reaction vessel was sealed
6. 6
   其他irradiation at 120° C. for 1800 s
7. 7
   过滤The reaction mixture was filtered through a plug of celite and
8. 8
   浓缩concentrated in vacuo
9. 9
   其他The crude product was purified by chromatography (90/10/1 dichloromethane/methanol/ammonium hydroxide)

实验过程

In a 5 mL microwave reaction vessel was added N-((3R)-1-azabicyclo[2.2.2]oct-3-yl)-5-(bromo)benzo[d]isothiazole-3-carboxamide (133 mg, 0.37 mmol), tris(dibenzylideneacetone)dipalladium (0) (34 mg, 0.04 mmol), caesium bicarbonate (213 mg, 1.1 mmol), and (2′-dicyclohexylphosphanylbiphenyl-2-yl)dimethylamine (30 mg, 0.07 mmol). The vial was then evacuated and back-filled with argon gas. The mixture of solids was then diluted with morpholine (0.7 mL), dioxane (1 mL), and triethylamine (0.5 mL) and the reaction vessel was sealed. The reaction mixture was subjected to microwave irradiation at 120° C. for 1800 s. The reaction mixture was filtered through a plug of celite and concentrated in vacuo. The crude product was purified by chromatography (90/10/1 dichloromethane/methanol/ammonium hydroxide) to provide 47 mg (34%) of 6-morpholin-4-ylbenzo[d]isothiazole-3-carboxylic acid ((3R)-1-azabicyclo[2.2.2]oct-3-yl)amide as a colorless solid.

来源