تفاعل #1885059

معادلة التفاعل

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

المردود 74.0%

المذيبات

DCM

DCM

DCM

ظروف التفاعل

المعالجة

1. 1
   أخرىSynthesized
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
   أخرىthe phases were separated
6. 6
   استخلاصThe aqueous phase was extracted with DCM (5 mL)
7. 7
   غسيلwashed with saturated aqueous NaHCO3 (5×5 ml)
8. 8
   غسيلThe organic layer was washed with brine (5 mL)
9. 9
   تجفيفdried over MgSO4
10. 10
    أخرىabsorbed onto Celite
11. 11
    أخرىPurification by silica gel column chromatography (1-5% MeOH in DCM)

الإجراء التجريبي

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.

المصدر