Dimethylformamide → (R)-4-fluoro-N-(4-(3-hydroxy-2-oxopyrrolidin-1-yl)phenylsulfonyl)-N-(thiazol-2-yl)benzenesulfonamide

HRID 1670457Notes

Reaction equation

HRID 1670457 reaction equation
[OH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[CH:12]=[CH:11][C:10]([S:13]([NH:16][C:17]3[S:18][CH:19]=[CH:20][N:21]=3)(=[O:15])=[O:14])=[CH:9][CH:8]=2)[C:3]1=[O:22].CN(C=O)C.C(N(C(C)C)CC)(C)C.[F:37][C:38]1[CH:43]=[CH:42][C:41]([S:44](Cl)(=[O:46])=[O:45])=[CH:40][CH:39]=1>CO>[F:37][C:38]1[CH:43]=[CH:42][C:41]([S:44]([N:16]([S:13]([C:10]2[CH:11]=[CH:12][C:7]([N:4]3[CH2:5][CH2:6][C@@H:2]([OH:1])[C:3]3=[O:22])=[CH:8][CH:9]=2)(=[O:14])=[O:15])[C:17]2[S:18][CH:19]=[CH:20][N:21]=2)(=[O:46])=[O:45])=[CH:40][CH:39]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 95884-Fluorobenzenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 59466118(R)-4-(3-hydroxy-2-oxopyrrolidin-1-yl)-N-(thiazol-2-yl)benzenesulfonamide

Product 1

HCID 59593431(R)-4-fluoro-N-(4-(3-hydroxy-2-oxopyrrolidin-1-yl)phenylsulfonyl)-N-(thiazol-2-yl)benzenesulfonamideYield 89%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Synthesized according to General Procedure 30. To a stirring solution of (R)-4-(3-hydroxy-2-oxopyrrolidin-1-yl)-N-(thiazol-2-yl)benzenesulfonamide (5.0 g, 14.8 mmol) and DMF (25 mL), under N2, at 5° C. (ice bath) was added diisopropylethyamine (2.5 mL, 14.8 mmol). To this solution was added 4-fluorobenzenesulfonyl chloride (2.9 g, 14.8 mmol) portionwise over 10 minutes. The solution was stirred at ambient temperature for 20 minutes. To this solution was added MeOH (75 mL). The mixture was cooled to 5° C. via an ice bath and stirred for 30 minutes. The precipitate was filtered, washed with MeOH (20 mL), and vacuum dried to give the desired sulfonamide as a white solid (6.5 g, 13.1 mmol, 89% yield). 1H-NMR (400 MHz, DMSO) δ 8.03-7.96 (m, 2H), 7.83-7.80 (m, 2H), 7.72 (d, J=5.1 Hz, 1H), 7.61 (dd, J=1.8, 7.1 Hz, 1H), 7.59 (s, 1H), 7.37 (s, 1H), 7.37 (dd, J=2.0, 15.6 Hz, 1H), 7.02 (d, J=5.1 Hz, 1H), 5.88 (d, J=5.9 Hz, 1H), 4.38-4.32 (m, 1H), 3.83-3.78 (m, 1H), 3.71 (td, J=9.5, 5.4 Hz, 1H), 2.52-2.42 (m, 1H), 1.87 (td, J=9.4, 4.1 Hz, 1H). LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=498.3; tR=1.32 min.

Workup

  1. customSynthesized
  2. temperatureThe mixture was cooled to 5° C. via an ice bath
  3. stirringstirred for 30 minutes
  4. filtrationThe precipitate was filtered
  5. washwashed with MeOH (20 mL), and vacuum
  6. customdried

Sources & evidence

ORD record
ord-dd2ed665665842359566e84d25d62a91
Source dataset
uspto-grants-2011_08
Patent number
US07994166B2

Reaction notes

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