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

温度

-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レコード

ord-e1a1aea91602464094b691e3d90de553

出典データセット

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08343763B2