Chloride → 5-[3-Fluoro-4-(methylsulfonyl)phenyl]-2-methyl-1-[4-(4-thiazolyl)phenyl]-1H-pyrrole

HRID 2086695Notes

Reaction equation

HRID 2086695 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH3:13])=[CH:11][CH:10]=[C:9]2[C:14]2[CH:19]=[CH:18][C:17]([S:20]([CH3:23])(=[O:22])=[O:21])=[C:16]([F:24])[CH:15]=2)=[CH:4][CH:3]=1.C([Sn](CCCC)(CCCC)[C:30]1[N:31]=[CH:32][S:33][CH:34]=1)CCC.[Cl-]>O1CCOCC1.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:24][C:16]1[CH:15]=[C:14]([C:9]2[N:8]([C:5]3[CH:6]=[CH:7][C:2]([C:30]4[N:31]=[CH:32][S:33][CH:34]=4)=[CH:3][CH:4]=3)[C:12]([CH3:13])=[CH:11][CH:10]=2)[CH:19]=[CH:18][C:17]=1[S:20]([CH3:23])(=[O:22])=[O:21]

Participants

6

Reactant 3

HCID 312ChlorideHCID 27632584-(Tri-n-butylstannyl)thiazoleHCID 223168021-(4-Bromophenyl)-2-(3-fluoro-4-(methylsulfonyl)phenyl]-5-methyl-1H-pyrrole

Product 1

HCID 223166015-[3-Fluoro-4-(methylsulfonyl)phenyl]-2-methyl-1-[4-(4-thiazolyl)phenyl]-1H-pyrroleYield 68.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of 1-(4-bromophenyl)-2-[3-fluoro-4-(methylsulfonyl)phenyl]-5-methyl-1H-pyrrole (0.318 g, 0.78 mmol, Example 35, step 3) in 1,4-dioxane (12 mL) was added 4-(tributylstannyl)thiazole (0.35 g, 0.94 mmol), lithiun chloride (0.083 g, 1.95 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.090 g, 0.078 mmol) at room temperature under nitrogen. The mixture was heated at reflux temperature for 3.5 hours. After cooling, volatiles were removed by evaporation. The residue was redissolved in ethyl acetate (30 mL) and the whole washed with water and brine. After dried over MgSO4 and concentration in vacuo. The crude mixture was purified by flash chromatography eluting with hexane/ethyl acetate (3/1). The resulting solid was recrystallized from ethyl acetate-hexane to give the title compound (0.221 g, 68.8% yield).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux temperature for 3.5 hours
  3. temperatureAfter cooling
  4. customvolatiles were removed by evaporation
  5. dissolutionThe residue was redissolved in ethyl acetate (30 mL)
  6. washthe whole washed with water and brine
  7. dry with materialAfter dried over MgSO4 and concentration in vacuo
  8. customThe crude mixture was purified by flash chromatography
  9. washeluting with hexane/ethyl acetate (3/1)
  10. customThe resulting solid was recrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-f145add31ee14cf289835f51c204170a
Source dataset
uspto-grants-2004_04
Patent number
US06727238B2

Reaction notes

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