Potassium Carbonate → 5-chloro-4-(6-chloro-2'-fluoro-4-iodobiphenyl-3-yloxy)-N-(2,4-dimethoxybenzyl)-2-fluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide

HRID 1619694Notes

Reaction equation

HRID 1619694 reaction equation
[Cl:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[F:14])=[CH:6][C:5]([OH:15])=[C:4]([I:16])[CH:3]=1.[Cl:17][C:18]1[C:19](F)=[CH:20][C:21]([F:44])=[C:22]([S:24]([N:27]([CH2:33][C:34]2[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][C:35]=2[O:42][CH3:43])[C:28]2[S:29][CH:30]=[N:31][N:32]=2)(=[O:26])=[O:25])[CH:23]=1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O>[Cl:17][C:18]1[C:19]([O:15][C:5]2[CH:6]=[C:7]([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=3[F:14])[C:2]([Cl:1])=[CH:3][C:4]=2[I:16])=[CH:20][C:21]([F:44])=[C:22]([S:24]([N:27]([CH2:33][C:34]2[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][C:35]=2[O:42][CH3:43])[C:28]2[S:29][CH:30]=[N:31][N:32]=2)(=[O:25])=[O:26])[CH:23]=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 580423466-Chloro-2'-fluoro-4-iodobiphenyl-3-ol

Product 1

HCID 580422945-chloro-4-(6-chloro-2'-fluoro-4-iodobiphenyl-3-yloxy)-N-(2,4-dimethoxybenzyl)-2-fluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

6-Chloro-2′-fluoro-4-iodobiphenyl-3-ol (Preparation 94, 651 mg, 1.75 mmol) was added to a mixture of 5-chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide (Preparation 16, 671 mg, 1.85 mmol) and potassium carbonate (967 mg, 7.00 mmol) in dimethylsulfoxide (17.5 mL) and the mixture stirred at room temperature for 18 hours. The reaction was quenched by addition of 0.75 N aq. sodium hydroxide (30.0 mL) and ethyl acetate (30 mL). The aqueous layer was separated and extracted with ethyl acetate (3×10 mL). The combined organic phases were washed with brine (10 mL), dried over MgSO4, filtered and evaporated. The residue was purified on silica, eluting with ethyl acetate:heptanes (3:7) to give the title compound as a mixture of regioisomers (930 mg, 67%). Further purification by preparative HPLC using acetonitrile/water as eluent (5/95-95/5, Phenomenex Luna C18 5 u 110 A 21.2×150 mm) gave the title compound (600 mg, 43%) as a white solid.

Workup

  1. customThe reaction was quenched by addition of 0.75 N aq. sodium hydroxide (30.0 mL) and ethyl acetate (30 mL)
  2. customThe aqueous layer was separated
  3. extractionextracted with ethyl acetate (3×10 mL)
  4. washThe combined organic phases were washed with brine (10 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified on silica
  9. washeluting with ethyl acetate:heptanes (3:7)

Sources & evidence

ORD record
ord-ef1e854ab3f447ed8108acbb17de2998
Source dataset
uspto-grants-2014_07
Patent number
US08772293B2

Reaction notes

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