反应 #1885059

反应方程式

triflic anhydride

3-(4-chloro-3-methylphenyl)pyrrolidine

NaHCO3

DIEA

Morpholine

(R)-4-fluoro-N-(4-(3-hydroxy-2-oxopyrrolidin-1-yl)phenylsulfonyl]-N-(thiazol-2-yl)benzenesulfonamide

→

4-[(3′S)-3-(4-chloro-3-methylphenyl]-2′-oxo-1,3′-bipyrrolidin-1′-yl)-N-(thiazol-2-yl)benzenesulfonamide

收率 74.0%

溶剂

DCM

DCM

DCM

反应条件

后处理

1. 1
   其他Synthesized
2. 2
   workup.ADDITIONwas added dropwise over 5 minutes
3. 3
   workup.STIRRINGthe reaction mixture was stirred at −20° C. for 1.5 hours
4. 4
   workup.ADDITIONwas added
5. 5
   其他the phases were separated
6. 6
   萃取The aqueous phase was extracted with DCM (5 mL)
7. 7
   洗涤washed with saturated aqueous NaHCO3 (5×5 ml)
8. 8
   洗涤The organic layer was washed with brine (5 mL)
9. 9
   干燥dried over MgSO4
10. 10
    其他absorbed onto Celite
11. 11
    其他Purification by silica gel column chromatography (1-5% MeOH in DCM)

实验过程

Synthesized according to General Procedure 9. To a stirred suspension of [(R)-4-fluoro-N-(4-(3-hydroxy-2-oxopyrrolidin-1-yl)phenylsulfonyl]-N-(thiazol-2-yl)benzenesulfonamide (500 mg, 1.01 mmol) in anhydrous DCM (10 mL) under nitrogen at −20° C. was added DIEA (0.88 mL, 5.03 mmol) followed by the dropwise addition of triflic anhydride (0.22 mL, 1.31 mmol) over 5 min. After stirring for 15 minutes at −20° C. a solution of 3-(4-chloro-3-methylphenyl)pyrrolidine (197 mg, 1.01 mmol) in anhydrous DCM (1 mL) was added dropwise over 5 minutes. The reaction mixture was continued to stir at −20° C. for 1 hour. Morpholine (0.35 mL, 4.02 mmol) was added and the reaction mixture was stirred at −20° C. for 1.5 hours. The reaction mixture was then poured into saturated aqueous NaHCO3 (10 mL), DCM (5 mL) was added and the phases were separated. The aqueous phase was extracted with DCM (5 mL). The organic portions were combined and washed with saturated aqueous NaHCO3 (5×5 ml). The organic layer was washed with brine (5 mL), dried over MgSO4 and absorbed onto Celite. Purification by silica gel column chromatography (1-5% MeOH in DCM) afforded 4-[(3′S)-3-(4-chloro-3-methylphenyl]-2′-oxo-1,3′-bipyrrolidin-1′-yl)-N-(thiazol-2-yl)benzenesulfonamide as a white solid (385 mg, 0.74 mmol, 74% yield). LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=517.0; tR=1.11 min.

来源