Morpholine → 4-[(3R,3'S)-3-(3,5-Dichlorophenyl)-2'-oxo-1,3'-bipyrrolidin-1'-yl]-N-(thiazol-2-yl)benzenesulfonamide

HRID 2261493Notes

Reaction equation

HRID 2261493 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]2[CH2:13][CH2:12][N:11]([C@H:14]3[CH2:18][CH2:17][N:16]([C:19]4[CH:24]=[CH:23][C:22]([S:25]([N:28](S(C5C=CC(OC)=CC=5)(=O)=O)[C:29]5[S:30][CH:31]=[CH:32][N:33]=5)(=[O:27])=[O:26])=[CH:21][CH:20]=4)[C:15]3=[O:45])[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.N1CCOCC1>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]2[CH2:13][CH2:12][N:11]([C@H:14]3[CH2:18][CH2:17][N:16]([C:19]4[CH:20]=[CH:21][C:22]([S:25]([NH:28][C:29]5[S:30][CH:31]=[CH:32][N:33]=5)(=[O:26])=[O:27])=[CH:23][CH:24]=4)[C:15]3=[O:45])[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

4

Reactant 2

HCID 8083MorpholineHCID 595934514-[(3R,3'S)-3-(3,5-dichlorophenyl)-2'-oxo-1,3'-bipyrrolidin-1'-yl]-N-(4-methoxyphenylsulfonyl)-N-(thiazol-2-yl)benzenesulfonamide

Product 1

HCID 446034274-[(3R,3'S)-3-(3,5-Dichlorophenyl)-2'-oxo-1,3'-bipyrrolidin-1'-yl]-N-(thiazol-2-yl)benzenesulfonamideYield 77.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Synthesized according to General Procedure 14. To a stirred solution of 4-[(3R,3′S)-3-(3,5-dichlorophenyl)-2′-oxo-1,3′-bipyrrolidin-1′-yl]-N-(4-methoxyphenylsulfonyl)-N-(thiazol-2-yl)benzenesulfonamide (40 g, 56.5 mmol) in anhydrous DCM (320 mL) under nitrogen at 0° C. was added morpholine (5.42 g, 5.42 mL, 62.2 mmol) dropwise over 5 minutes. The cooling bath was removed and the reaction mixture was allowed to warm up to RT. Stirring was continued at RT for 2 hours during which time the product precipitated. The solid was filtered, washed with ethyl acetate (100 mL) and dried under vacuum to constant weight to provide 4-[(3R,3′S)-3-(3,5-dichlorophenyl)-2′-oxo-1,3′-bipyrrolidin-1′-yl]-N-(thiazol-2-yl)benzenesulfonamide as a white solid (23.50 g, 43.7 mmol, 77% yield). 1H-NMR (400 MHz, DMSO-d6) δ 7.84-7.77 (m, 4H), 7.43-7.37 (m, 3H), 7.24 (d, J=4.6 Hz, 1H), 6.81 (d, J=4.6 Hz, 1H), 3.83-3.72 (m, 2H), 3.58 (t, J=8.8 Hz, 1H), 3.07-2.96 (m, 3H), 2.87 (td, J=8.6, 4.3 Hz, 1H), 2.34-2.20 (m, 2H), 2.11-2.02 (m, 1H) and 1.74 (dt, J=19.9, 6.9 Hz, 1H) ppm. LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=537.3; tR=1.30 min. SFC (Chiralpak AS-H, (0.46×25 cm), 40% methanol (1% DEA)/CO2, 3 ML/min): tR=13.0 min.

Workup

  1. customSynthesized
  2. customThe cooling bath was removed
  3. customthe product precipitated
  4. filtrationThe solid was filtered
  5. washwashed with ethyl acetate (100 mL)
  6. customdried under vacuum to constant weight

Sources & evidence

ORD record
ord-5bc08df8521f4b888e3b59edf1c347bb
Source dataset
uspto-grants-2010_12
Patent number
US07846954B2

Reaction notes

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