반응 #1885059

반응 방정식

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

수율 74.0%

용매

DCM

DCM

DCM

반응 조건

후처리

1. 1
   기타Synthesized
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
   기타the phases were separated
6. 6
   추출The aqueous phase was extracted with DCM (5 mL)
7. 7
   세척washed with saturated aqueous NaHCO3 (5×5 ml)
8. 8
   세척The organic layer was washed with brine (5 mL)
9. 9
   건조dried over MgSO4
10. 10
    기타absorbed onto Celite
11. 11
    기타Purification by silica gel column chromatography (1-5% MeOH in DCM)

실험 절차

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.

출처