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

HRID 2261490Notes

Reaction equation

HRID 2261490 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.CCN(C(C)C)C(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 8. To a stirred 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 DIEA (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 [(R)-4-fluoro-N-(4-(3-hydroxy-2-oxopyrrolidin-1-yl)phenylsulfonyl]-N-(thiazol-2-yl)benzenesulfonamide 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-2222ebaf94164853a014fec1d26103a5
Source dataset
uspto-grants-2010_12
Patent number
US07846954B2

Reaction notes

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