Potassium Carbonate → 5-chloro-N-(2,4-dimethoxybenzyl)-2-fluoro-4-{2-[3-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]-4-(trifluoromethyl)phenoxy}-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide

HRID 1692352Notes

Reaction equation

HRID 1692352 reaction equation
[N+:1]([C:4]1[C:8]([C:9]2[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][C:10]=2[OH:19])=[CH:7][N:6]([CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][O:21]2)[N:5]=1)([O-:3])=[O:2].C(=O)([O-])[O-].[K+].[K+].[Cl:32][C:33]1[C:34](F)=[CH:35][C:36]([F:59])=[C:37]([S:39]([N:42]([CH2:48][C:49]2[CH:54]=[CH:53][C:52]([O:55][CH3:56])=[CH:51][C:50]=2[O:57][CH3:58])[C:43]2[S:44][CH:45]=[N:46][N:47]=2)(=[O:41])=[O:40])[CH:38]=1>CS(C)=O.C(OCC)(=O)C>[Cl:32][C:33]1[C:34]([O:19][C:10]2[CH:11]=[CH:12][C:13]([C:15]([F:17])([F:18])[F:16])=[CH:14][C:9]=2[C:8]2[C:4]([N+:1]([O-:3])=[O:2])=[N:5][N:6]([CH:20]3[CH2:25][CH2:24][CH2:23][CH2:22][O:21]3)[CH:7]=2)=[CH:35][C:36]([F:59])=[C:37]([S:39]([N:42]([CH2:48][C:49]2[CH:54]=[CH:53][C:52]([O:55][CH3:56])=[CH:51][C:50]=2[O:57][CH3:58])[C:43]2[S:44][CH:45]=[N:46][N:47]=2)(=[O:40])=[O:41])[CH:38]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 580422535-chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamideHCID 669055812-[3-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]-4-(trifluoromethyl)phenol

Product 1

HCID 669058755-chloro-N-(2,4-dimethoxybenzyl)-2-fluoro-4-{2-[3-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]-4-(trifluoromethyl)phenoxy}-N-1,3,4-thiadiazol-2-ylbenzenesulfonamideYield 69.3%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-[3-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]-4-(trifluoromethyl)phenol (Preparation 868, 2.069 g, 5.791 mmol) in dimethyl sulfoxide (34 mL) was added potassium carbonate (1.66 g, 12.0 mmol). After stirring for 10 minutes, 5-chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide (Preparation 247, 2.67 g, 5.78 mmol) was added. After stirring at room temperature for 16 hours, the reaction solution was diluted with ethyl acetate and washed with water and brine. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated. Purification by automated flash column chromatography using a 0-100% ethyl acetate/hexanes gradient and a 40 g column gave the title compound (3.20 g, 69%) as a clear oil.

Workup

  1. stirringAfter stirring at room temperature for 16 hours
  2. washwashed with water and brine
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by automated flash column chromatography

Sources & evidence

ORD record
ord-5cfa9931f0ea406fb5cffb0af5b06386
Source dataset
uspto-grants-2012_04
Patent number
US08153814B2

Reaction notes

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