Trifluoroacetic acid → 2,5-difluoro-4-[2-(1H-pyrazol-5-yl)-4-(trifluoromethyl)phenoxy]-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide

HRID 1401907Notes

Reaction equation

HRID 1401907 reaction equation
COC1C=C(OC)C=CC=1C[N:6]([C:30]1[S:34][N:33]=[CH:32][N:31]=1)[S:7]([C:10]1[CH:15]=[C:14]([F:16])[C:13]([O:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][C:19]=2I)=[CH:12][C:11]=1[F:29])(=[O:9])=[O:8].C(=O)([O-])[O-].[K+].[K+].C(OC[N:51]1[C:55](B2OC(C)(C)C(C)(C)O2)=[CH:54][CH:53]=[N:52]1)C.FC(F)(F)C(O)=O>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:29][C:11]1[CH:12]=[C:13]([O:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][C:19]=2[C:53]2[NH:52][N:51]=[CH:55][CH:54]=2)[C:14]([F:16])=[CH:15][C:10]=1[S:7]([NH:6][C:30]1[S:34][N:33]=[CH:32][N:31]=1)(=[O:9])=[O:8]

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 59436549N-(2,4-dimethoxybenzyl)-2,5-difluoro-4-[2-iodo-4-(trifluoromethyl)phenoxy]-N-1,2,4-thiadiazol-5-ylbenzenesulfonamideHCID 594366031-(ethoxymethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Product 1

HCID 468409472,5-difluoro-4-[2-(1H-pyrazol-5-yl)-4-(trifluoromethyl)phenoxy]-N-1,2,4-thiadiazol-5-ylbenzenesulfonamideYield 9%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of N-(2,4-dimethoxybenzyl)-2,5-difluoro-4-[2-iodo-4-(trifluoromethyl)phenoxy]-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide (Preparation 363, 100 mg, 0.14 mmol), potassium carbonate (48 mg, 1.12 mmol) and 1-(ethoxymethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (Preparation 337, 70 mg, 0.28 mmol) in 1,4-dioxane (5 mL) and water (2 mL) was degassed and palladium tetrakis (16 mg, 0.014 mmol) added before heating at 80° C. for 16 hours. Dicholoromethane (20 mL) and water (10 mL) were added and the organics separated and evaporated in vacuo to afford the crude product. Dicholoromethane (10 mL) and trifluoroacetic acid (5 mL) were added and the reaction mixture was stirred at room temperature for 16 hours before concentrating in vacuo. Hydrochloric acid (4 M in 1,4-dioxane, 10 mL) was added and the reaction mixture was stirred for 16 hours before concentrating in vacuo. The residue was purified by reverse phase chromatography to afford the desired product, 6 mg, 9% yield.

Workup

  1. customwas degassed
  2. customthe organics separated
  3. customevaporated in vacuo
  4. customto afford the crude product
  5. concentrationbefore concentrating in vacuo
  6. additionHydrochloric acid (4 M in 1,4-dioxane, 10 mL) was added
  7. stirringthe reaction mixture was stirred for 16 hours
  8. concentrationbefore concentrating in vacuo
  9. customThe residue was purified by reverse phase chromatography

Sources & evidence

ORD record
ord-a116ad9abd594b04a8df28c6486c2666
Source dataset
uspto-grants-2014_12
Patent number
US08907101B2

Reaction notes

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