Dimethylacetamide → 2-fluoro-N-(thiazol-2-yl)-4-(1-(4-(trifluoromethyl)benzyl)-1H-pyrazol-4-ylamino)benzenesulfonamide

HRID 1644655Notes

Reaction equation

HRID 1644655 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2[S:13][CH:14]=[CH:15][N:16]=2)(=[O:10])=[O:9])=[C:4]([F:17])[CH:3]=1.[F:18][C:19]([F:34])([F:33])[C:20]1[CH:32]=[CH:31][C:23]([CH2:24][N:25]2[CH:29]=[C:28]([NH2:30])[CH:27]=[N:26]2)=[CH:22][CH:21]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.CN(C)C(=O)C.CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:17][C:4]1[CH:3]=[C:2]([NH:30][C:28]2[CH:27]=[N:26][N:25]([CH2:24][C:23]3[CH:22]=[CH:21][C:20]([C:19]([F:34])([F:33])[F:18])=[CH:32][CH:31]=3)[CH:29]=2)[CH:7]=[CH:6][C:5]=1[S:8]([NH:11][C:12]1[S:13][CH:14]=[CH:15][N:16]=1)(=[O:10])=[O:9]

Participants

7

Reactant 5

HCID 31374DimethylacetamideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 251383534-Bromo-2-fluoro-N-thiazol-2-yl-benzenesulfonamideHCID 575511981-(4-(trifluoromethyl)benzyl)-1H-pyrazol-4-amine

Product 1

HCID 575512532-fluoro-N-(thiazol-2-yl)-4-(1-(4-(trifluoromethyl)benzyl)-1H-pyrazol-4-ylamino)benzenesulfonamide

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
120 °C

Procedure

4-Bromo-2-fluoro-N-thiazol-2-yl-benzenesulfonamide (0.337 g, 1.00 mmol), 1-(4-Trifluoromethyl-benzyl)-1H-pyrazol-4-ylamine (0.242 g, 1.00 mmol), Tris(dibenzylideneacetone)dipalladium(0) (0.037 g, 0.040 mmol), and 9,9-DIMETHYL-4,5-BIS(DIPHENYLPHOSPHINO)XANTHENE (0.069 g, 0.12 mmol), were mixed in anhydrous N,N-Dimethylacetamide (10 mL, 100 mmol). The solution was sparged with argon for 10 minutes. Sodium tert-butoxide (0.290 g, 3.02 mmol) was added and the reaction was heated in the microwave for 5 minutes at 120° C. The crude reaction was partitioned between 1N HCl and chloroform. The organic phase was separated and the aqueous phase washed a second time with chloroform. The combined organic phase was washed with brine and dried over magnesium sulfate, then evaporated onto celite. The product was purified by column chromatography, chloroform to 10% methanol-chloroform gradient elution. Product fractions were combined and evaporated to a residue. The product was purified by reverse phase HPLC. (Phenomenex 100×21.2 mm 10 micron C18 column. 20 mL/min. Gradient 85% A to 100% B over 25 min. Solvent A: 7800 water/200 acetonitrile/8 TFA.).

Workup

  1. customThe solution was sparged with argon for 10 minutes
  2. customThe crude reaction
  3. customwas partitioned between 1N HCl and chloroform
  4. customThe organic phase was separated
  5. washthe aqueous phase washed a second time with chloroform
  6. washThe combined organic phase was washed with brine
  7. dry with materialdried over magnesium sulfate
  8. customevaporated onto celite
  9. customThe product was purified by column chromatography, chloroform to 10% methanol-chloroform gradient elution
  10. customevaporated to a residue
  11. customThe product was purified by reverse phase HPLC
  12. custom(Phenomenex 100×21.2 mm 10 micron C18 column. 20 mL/min. Gradient 85% A to 100% B over 25 min. Solvent A: 7800 water/200 acetonitrile/8 TFA.)

Sources & evidence

ORD record
ord-96cb1b9e3c634571ac66d618811403dd
Source dataset
uspto-grants-2012_02
Patent number
US08124610B2

Reaction notes

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