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

HRID 1797877
Notes
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Reaction equation

HRID 1797877 reaction equation
FC1C=CC(S([N:11]([S:17]([C:20]2[CH:25]=[CH:24][C:23]([N:26]3[CH2:30][CH2:29][C@@H:28](O)[C:27]3=[O:32])=[CH:22][CH:21]=2)(=[O:19])=[O:18])[C:12]2[S:13][CH:14]=[CH:15][N:16]=2)(=O)=O)=CC=1.CCN(C(C)C)C(C)C.S(OS(C(F)(F)F)(=O)=O)(C(F)(F)F)(=O)=O.[Cl:57][C:58]1[CH:63]=[CH:62][C:61]([CH:64]2[CH2:68][CH2:67][NH:66][CH2:65]2)=[CH:60][C:59]=1[CH3:69].N1CCOCC1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[Cl:57][C:58]1[CH:63]=[CH:62][C:61]([CH:64]2[CH2:68][CH2:67][N:66]([C@H:28]3[CH2:29][CH2:30][N:26]([C:23]4[CH:22]=[CH:21][C:20]([S:17]([NH:11][C:12]5[S:13][CH:14]=[CH:15][N:16]=5)(=[O:19])=[O:18])=[CH:25][CH:24]=4)[C:27]3=[O:32])[CH2:65]2)=[CH:60][C:59]=1[CH3:69]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 6

HCID 8083MorpholineHCID 67749Trifluoromethanesulfonic anhydrideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 59593431(R)-4-fluoro-N-(4-(3-hydroxy-2-oxopyrrolidin-1-yl)phenylsulfonyl)-N-(thiazol-2-yl)benzenesulfonamideHCID 595934633-(4-Chloro-3-methylphenyl)pyrrolidine

Product 1

HCID 595934274-[(3'S)-3-(4-chloro-3-methylphenyl]-2'-oxo-1,3'-bipyrrolidin-1'-yl)-N-(thiazol-2-yl)benzenesulfonamideYield 74%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-20 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-e1a1aea91602464094b691e3d90de553
Source dataset
uspto-grants-2013_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08343763B2

Reaction notes

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