4-Methoxybenzenesulfonyl chloride → (R)-4-(3-hydroxy-2-oxopyrrolidin-1-yl)-N-(4-methoxyphenylsulfonyl)-N-(thiazol-2-yl)benzenesulfonamide

HRID 2261492Notes

Reaction equation

HRID 2261492 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].CCN(C(C)C)C(C)C.[CH3:32][O:33][C:34]1[CH:39]=[CH:38][C:37]([S:40](Cl)(=[O:42])=[O:41])=[CH:36][CH:35]=1>C(Cl)Cl>[OH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[CH:12]=[CH:11][C:10]([S:13]([N:16]([S:40]([C:37]3[CH:36]=[CH:35][C:34]([O:33][CH3:32])=[CH:39][CH:38]=3)(=[O:42])=[O:41])[C:17]3[S:18][CH:19]=[CH:20][N:21]=3)(=[O:14])=[O:15])=[CH:9][CH:8]=2)[C:3]1=[O:22]

Participants

5

Reactant 3

HCID 74014-Methoxybenzenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 59466118(R)-4-(3-hydroxy-2-oxopyrrolidin-1-yl)-N-(thiazol-2-yl)benzenesulfonamide

Product 1

HCID 59593437(R)-4-(3-hydroxy-2-oxopyrrolidin-1-yl)-N-(4-methoxyphenylsulfonyl)-N-(thiazol-2-yl)benzenesulfonamideYield 90.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Synthesized according to General Procedure 8. To a stirred suspension of (R)-4-(3-hydroxy-2-oxopyrrolidin-1-yl)-N-(thiazol-2-yl)benzenesulfonamide (41 g, 0.121 mol) in DCM (205 mL) under N2 at 0° C. was added DIEA (15.6 g, 21 mL, 0.121 mol). To this suspension at 0° C. was added 4-methoxybenzenesulfonyl chloride (25 g, 0.121 mol) portionwise over 15 minutes. The cooling bath was removed and the suspension was allowed to warm to RT over 1 hour during which time the reaction mixture became a homogeneous solution. The solution was cooled to 0° C. and MeOH (2.05 L) was added. Stirring was continued at 0° C. After 10 minutes a precipitate formed. The resulting suspension was stirred at 0° C. for 30 minutes and then filtered. The filter cake was washed with MeOH (2×250 mL) and then dried under vacuum to constant weight to provide (R)-4-(3-hydroxy-2-oxopyrrolidin-1-yl)-N-(4-methoxyphenylsulfonyl)-N-(thiazol-2-yl)benzenesulfonamide as a white solid (55.49 g, 0.109 mol, 90% yield). 1H-NMR (400 MHz, DMSO-d6) δ 7.86-7.80 (m, 4H), 7.70 (d, J=5.1 Hz, 1H), 7.60 (d, J=9.0 Hz, 2H), 7.03-6.98 (m, 3H), 5.88 (d, J=5.9 Hz, 1H), 4.38-4.32 (m, 1H), 3.85-3.77 (m, 1H), 3.81 (s, 3H), 3.70 (td, J=9.4, 5.4 Hz, 1H), 2.48-2.41 (m, 1H) and 1.92-1.82 (m, 1H) ppm. LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=510.0; tR=1.22 min.

Workup

  1. customSynthesized
  2. customThe cooling bath was removed
  3. temperatureThe solution was cooled to 0° C.
  4. additionMeOH (2.05 L) was added
  5. customwas continued at 0° C
  6. customAfter 10 minutes a precipitate formed
  7. stirringThe resulting suspension was stirred at 0° C. for 30 minutes
  8. filtrationfiltered
  9. washThe filter cake was washed with MeOH (2×250 mL)
  10. customdried under vacuum to constant weight

Sources & evidence

ORD record
ord-9ce9042f3cd2473f84a9122a87d77799
Source dataset
uspto-grants-2010_12
Patent number
US07846954B2

Reaction notes

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