1-(2-fluoro-4-hydroxyphenyl)-5-iodo-3-methyl-1H-pyrazole-4-carbonitrile → 5-(2,4-dimethylthiophen-3-yl)-1-(2-fluoro-4-hydroxyphenyl)-3-methyl-1H-pyrazole-4-carbonitrile

HRID 1410169Notes

Reaction equation

HRID 1410169 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:13](I)=[C:12]([C:15]#[N:16])[C:11]([CH3:17])=[N:10]1.C([Sn](CCCC)(CCCC)[C:23]1[C:27]([CH3:28])=[CH:26][S:25][C:24]=1[CH3:29])CCC>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:29][C:24]1[S:25][CH:26]=[C:27]([CH3:28])[C:23]=1[C:13]1[N:9]([C:3]2[CH:4]=[CH:5][C:6]([OH:8])=[CH:7][C:2]=2[F:1])[N:10]=[C:11]([CH3:17])[C:12]=1[C:15]#[N:16]

Participants

4

Reactant 2

HCID 671200291-(2-fluoro-4-hydroxyphenyl)-5-iodo-3-methyl-1H-pyrazole-4-carbonitrileHCID 67120033Tributyl(2,4-dimethylthiophen-3-yl)stannane

Product 1

HCID 671200575-(2,4-dimethylthiophen-3-yl)-1-(2-fluoro-4-hydroxyphenyl)-3-methyl-1H-pyrazole-4-carbonitrileYield 34%

Reagents, catalysts & solvents 1

HCID 178418476HCID 178418476, compoundCatalyst

Procedure

1-(2-fluoro-4-hydroxyphenyl)-5-iodo-3-methyl-1H-pyrazole-4-carbonitrile (40 mg, 0.12 mmol), tributyl(2,4-dimethylthiophen-3-yl)stannane (140.3 mg, 0.35 mmol) and PdCl2(PPh3)2 (24.55 mg, 0.03 mmol), were mixed with 0.5 mL degassed dioxane and 0.5 mL degassed DME under nitrogen in a microwave vial. The reaction was run at 145° C. in the microwave for 30 min. Water was added, the mixture was extracted with CH2Cl2 and the organic layer was concentrated. The crude product was purified on HPLC to give 5-(2,4-dimethylthiophen-3-yl)-1-(2-fluoro-4-hydroxyphenyl)-3-methyl-1H-pyrazole-4-carbonitrile (13 mg, 34%).

Workup

  1. customdegassed dioxane and 0.5 mL
  2. customdegassed DME under nitrogen in a microwave vial
  3. additionWater was added
  4. extractionthe mixture was extracted with CH2Cl2
  5. concentrationthe organic layer was concentrated
  6. customThe crude product was purified on HPLC

Sources & evidence

ORD record
ord-c53a1a088fa449ad9b7d4cc234faa3af
Source dataset
uspto-grants-2014_12
Patent number
US08921402B2

Reaction notes

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