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

온도

-20 °C

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.

1. customSynthesized
2. additionwas added dropwise over 5 minutes
3. stirringthe reaction mixture was stirred at −20° C. for 1.5 hours
4. additionwas added
5. customthe phases were separated
6. extractionThe aqueous phase was extracted with DCM (5 mL)
7. washwashed with saturated aqueous NaHCO3 (5×5 ml)
8. washThe organic layer was washed with brine (5 mL)
9. dry with materialdried over MgSO4
10. customabsorbed onto Celite
11. customPurification by silica gel column chromatography (1-5% MeOH in DCM)

ORD 기록

ord-a1700d7d44ea4721807ac7c578d02a82

출처 데이터셋

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08143297B2