Potassium Carbonate → 5-Chloro-4-(3'-cyano-3-(3-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)biphenyl-4-yloxy)-N-(2,4-dimethoxybenzyl)-2-fluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide

HRID 1619673Notes

Reaction equation

HRID 1619673 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]#[N:15])[CH:9]=2)=[CH:4][C:3]=1[C:16]1[C:17]([N+:27]([O-:29])=[O:28])=[N:18][N:19]([CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][O:22]2)[CH:20]=1.C(=O)([O-])[O-].[K+].[K+].[Cl:36][C:37]1[C:38](F)=[CH:39][C:40]([F:63])=[C:41]([S:43]([N:46]([CH2:52][C:53]2[CH:58]=[CH:57][C:56]([O:59][CH3:60])=[CH:55][C:54]=2[O:61][CH3:62])[C:47]2[S:48][CH:49]=[N:50][N:51]=2)(=[O:45])=[O:44])[CH:42]=1>CS(C)=O>[Cl:36][C:37]1[C:38]([O:1][C:2]2[CH:7]=[CH:6][C:5]([C:8]3[CH:13]=[CH:12][CH:11]=[C:10]([C:14]#[N:15])[CH:9]=3)=[CH:4][C:3]=2[C:16]2[C:17]([N+:27]([O-:29])=[O:28])=[N:18][N:19]([CH:21]3[CH2:26][CH2:25][CH2:24][CH2:23][O:22]3)[CH:20]=2)=[CH:39][C:40]([F:63])=[C:41]([S:43]([N:46]([CH2:52][C:53]2[CH:58]=[CH:57][C:56]([O:59][CH3:60])=[CH:55][C:54]=2[O:61][CH3:62])[C:47]2[S:48][CH:49]=[N:50][N:51]=2)(=[O:44])=[O:45])[CH:42]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 580422535-chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamideHCID 66656356HCID 66656356, compound

Product 1

HCID 580422935-Chloro-4-(3'-cyano-3-(3-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)biphenyl-4-yloxy)-N-(2,4-dimethoxybenzyl)-2-fluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamideYield 85%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

4′-Hydroxy-3′-(3-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)biphenyl-3-carbonitrile (Preparation 64, 250 mg, 0.64 mmol) was dissolved in DMSO (3.5 mL) and potassium carbonate (177 mg, 1.28 mmol) was added followed by 5-chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide (Preparation 16, 310 mg, 0.67 mmol). The reaction was stirred at room temperature for 1 hour and then partitioned between ethyl acetate and water. The aqueous phase was separated and extracted with EtOAc (3×5 mL) and the combined organic layers were washed with brine, dried over anhydrous MgSO4, filtered and concentrated in vacuo. The residue was purified on silica gel by Biotage™ (10% to 80% EtOAc in heptane over 12 CV) to give the title compound (451 mg, 85%) as a light yellow foam.

Workup

  1. custompartitioned between ethyl acetate and water
  2. customThe aqueous phase was separated
  3. extractionextracted with EtOAc (3×5 mL)
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified on silica gel by Biotage™ (10% to 80% EtOAc in heptane over 12 CV)

Sources & evidence

ORD record
ord-97610435b80547e98bdfdd9d92d46172
Source dataset
uspto-grants-2014_07
Patent number
US08772293B2

Reaction notes

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