Ethanol → 6-(1H-pyrazol-4-yl)isoquinoline

HRID 598895Notes

Reaction equation

HRID 598895 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][CH:6]=[CH:5]2.[NH:12]1[CH:16]=[C:15](B2OC(C)(C)C(C)(C)O2)[CH:14]=[N:13]1.C(=O)([O-])[O-].[Na+].[Na+].CCO>COCCOC.C([O-])(O)=O.[Na+].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.O>[NH:12]1[CH:16]=[C:15]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[CH:8]=[N:7][CH:6]=[CH:5]3)[CH:14]=[N:13]1

Participants

9

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 3136816-BromoisoquinolineHCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Product 1

HCID 579506126-(1H-pyrazol-4-yl)isoquinolineYield 37.8%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of 6-bromoisoquinoline (500 mg, 2.40 mmol) (commercially available from Kalexsyn Product List (Order Number 2003-005)), pyrazole-4-boronic acid pinacol ester (560 mg, 2.88 mmol) (commercially available from Acros Organics (Order Number 38294)), trans-dichlorobis(triphenylphosphine)palladium(II) (118 mg, 0.17 mmol), and sodium carbonate (764 mg, 7.21 mmol) in DME:EtOH:H2O=7:2:3 (4 mL) was heated at 140° C. for 10 minutes in a Biotage Initiator® microwave. After cooling to room temperature, the mixture was diluted with saturated aqueous NaHCO3 and extracted with 25% i-PrOH/CHCl3 (3×). The combined organic layers were dried over Na2SO4, filtered and adsorbed onto silica gel. The residue was purified using column chromatography (acetone/hexanes=0-50%) to provide the product as an off-white solid (177 mg, 37%). LCMS (API-ES) m/z: 196 (M+H+).

Workup

  1. extractionextracted with 25% i-PrOH/CHCl3 (3×)
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. customThe residue was purified

Sources & evidence

ORD record
ord-8faf3a660eaf4decbe9ca28c5bc40927
Source dataset
uspto-grants-2011_03
Patent number
US07897619B2

Reaction notes

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