Pyrazole → 4-Pyridinecarboxylic acid, 2-(1H-pyrazol-1-yl)-, methyl ester

HRID 594253Notes

Reaction equation

HRID 594253 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6].[NH:12]1[CH:16]=[CH:15][CH:14]=[N:13]1.CN[C@@H]1CCCC[C@H]1NC.C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1.[Cu]I.O>[N:12]1([C:2]2[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=2)[C:5]([O:7][CH3:8])=[O:6])[CH:16]=[CH:15][CH:14]=[N:13]1

Participants

8

Reactant 4

HCID 1048PyrazoleHCID 11430Potassium CarbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 38477682-Bromo-isonicotinic acid methyl ester

Product 1

HCID 690832694-Pyridinecarboxylic acid, 2-(1H-pyrazol-1-yl)-, methyl ester

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A mixture of commercially available methyl 2-bromoisonicotinate (500 mg; 2.31 mmol), 1H-pyrazole (157 mg; 2.31 mmol), trans-N,N′-dimethylcyclohexane-1,2-diamine (67 mg; 0.46 mmol), K2CO3 (685 mg; 4.86 mmol), and CuI (22 mg; 0.11 mmol) in anh. toluene (8 ml) was heated at reflux for 16 h. After cooling to rt, water was added, and the mixture was extracted with AcOEt. The mixed organic layers were dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (DCM/MeOH=20/1) afforded methyl 2-(1H-pyrazol-1-yl)isonicotinate as an off-white solid. LC-MS (conditions A): tR=0.67 min.; [M+H]+: 204.04 g/mol.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 16 h
  3. extractionthe mixture was extracted with AcOEt
  4. dry with materialThe mixed organic layers were dried over anh. MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to dryness under reduced pressure
  7. customPurification by FC (DCM/MeOH=20/1)

Sources & evidence

ORD record
ord-fe7b9d883a184bb49983791d1120547f
Source dataset
uspto-grants-2016_01
Patent number
US09242970B2

Reaction notes

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