反应 #53716

反应方程式

sodium hydrogencarbonate

trifluoroacetic acid

cesium carbonate

2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl

aniline

tert-butyl 3-iodo-5-(N-tert-butoxycarbonyl-2-methylsulfonylbenzenesulfonylamino)indazole-1-carboxylate

→

2-methylsulfonyl-N-(3-phenylamino-1H-indazol-5-yl)benzenesulfonamide

收率 47.5%

溶剂

dichloromethane

dichloromethane

1,2-dimethoxyethane

反应条件

后处理

1. 1
   其他the compound is prepared
2. 2
   其他Each reaction is prepared
3. 3
   其他The tube is sealed with the stopper
4. 4
   其他provided for this purpose
5. 5
   其他for 5 minutes
6. 6
   其他at 120° C
7. 7
   过滤The catalyst is filtered through Celite® 535
8. 8
   其他the four reaction crudes
9. 9
   浓缩concentrated to dryness under reduced pressure in the rotary evaporator
10. 10
    其他purified by preparative LC/MS (conditions A)
11. 11
    workup.ADDITIONThe fractions containing the protected intermediate compound
12. 12
    浓缩concentrated under reduced pressure
13. 13
    其他The yellow oil obtained
14. 14
    干燥the organic phase is dried over magnesium sulfate
15. 15
    浓缩the solvent is concentrated to dryness under reduced pressure
16. 16
    其他a rotary evaporator

实验过程

2-Methylsulfonyl-N-(3-phenylamino-1H-indazol-5-yl)benzenesulfonamide can be obtained in the following way: the compound is prepared by reacting under microwave radiation on a Personal Chemistry Emrys Optimizer device. Four identical reactions are carried out. Each reaction is prepared as follows: 60 mg of tert-butyl 3-iodo-5-(N-tert-butoxycarbonyl-2-methylsulfonylbenzenesulfonylamino)indazole-1-carboxylate are placed in a Personal Chemistry SmithProcessVial™ tube with a maximum volume of 5 ml. 404 mg of cesium carbonate, 35.9 mg of 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl, 12.1 mg of tris(dibenzylideneacetone)dipalladium[0] and 29 μl of aniline are then added. 4 ml of 1,2-dimethoxyethane are then added. The tube is sealed with the stopper provided for this purpose and the reaction is subjected to microwave radiation for 5 minutes at 120° C. The other parameters are those recommended by the constructor. The catalyst is filtered through Celite® 535 and the four reaction crudes are pooled, concentrated to dryness under reduced pressure in the rotary evaporator and purified by preparative LC/MS (conditions A). The fractions containing the protected intermediate compound are pooled and concentrated under reduced pressure. The yellow oil obtained is dissolved in 2 ml of dichloromethane and then 500 μl of trifluoroacetic acid are added. The solution is stirred for 2 hours at ambient temperature, until the starting product has disappeared. 10 ml of dichloromethane and 10 ml of a saturated sodium hydrogencarbonate solution are then added. When no more gas is being given off, the organic phase is dried over magnesium sulfate and the solvent is concentrated to dryness under reduced pressure and a rotary evaporator. 18.6 mg of 2-methylsulfonyl-N-(3-phenylamino-1H-indazol-5-yl)benzenesulfonamide are obtained in the form of a yellow oil (analytical LC/MS analysis: Tr=3.49 minutes; [M+H]+=443.09).

来源