2,5-Hexanedione → 5-(2,5-dimethyl-1H-pyrrol-1-yl)-1-(2-fluoro-4-hydroxyphenyl)-3-methyl-1H-pyrazole-4-carbonitrile

HRID 242193Notes

Reaction equation

HRID 242193 reaction equation
[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][C:8]=2[F:14])[N:5]=[C:4]([CH3:15])[C:3]=1[C:16]#[N:17].[CH2:18]([CH2:22][C:23](=O)[CH3:24])[C:19]([CH3:21])=O.CCOC(C)=O>CC(OCC1C2C(=CC=CC=2)C(COC(C)=O)=C2C=1C=CC=C2)=O>[CH3:24][C:23]1[N:1]([C:2]2[N:6]([C:7]3[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][C:8]=3[F:14])[N:5]=[C:4]([CH3:15])[C:3]=2[C:16]#[N:17])[C:19]([CH3:21])=[CH:18][CH:22]=1

Participants

5

Reactant 3

HCID 80352,5-HexanedioneHCID 8857Ethyl AcetateHCID 671200435-amino-1-(2-fluoro-4-hydroxyphenyl)-3-methyl-1H-pyrazole-4-carbonitrile

Product 1

HCID 671200565-(2,5-dimethyl-1H-pyrrol-1-yl)-1-(2-fluoro-4-hydroxyphenyl)-3-methyl-1H-pyrazole-4-carbonitrileYield 99%

Reagents, catalysts & solvents 1

HCID 613145Acetic acid 10-acetoxymethyl-anthracen-9-ylmethyl esterSolvent

Procedure

A solution of 5-amino-1-(2-fluoro-4-hydroxyphenyl)-3-methyl-1H-pyrazole-4-carbonitrile (100 mg, 0.43 mmol) and acetonylacetone (507 μL, 4.31 mmol) in glacial acetic (3 mL) acid was heated at 140° C. in the micro for 30 min. The mixture was transferred to a round bottom flask using EtOAc and evaporated, toluene was added and again evaporated, CH2Cl2 and silica was finally added and the mixture was evaporated to dryness. Purification using silica chromatography (short plug) gave 5-(2,5-dimethyl-1H-pyrrol-1-yl)-1-(2-fluoro-4-hydroxyphenyl)-3-methyl-1H-pyrazole-4-carbonitrile (132 mg, 99%) as a 1:1 mixture with the starting material acetonylacetone. The product was used as such in the next step.

Workup

  1. customThe mixture was transferred to a round bottom flask
  2. customevaporated
  3. additiontoluene was added
  4. customagain evaporated
  5. additionCH2Cl2 and silica was finally added
  6. customthe mixture was evaporated to dryness
  7. customPurification

Sources & evidence

ORD record
ord-ee113c1f054b4bb19a92df2010d44390
Source dataset
uspto-grants-2014_02
Patent number
US08653112B2

Reaction notes

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