4-Chloropyridine-2-carboxamide → 4-((6-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamido)pyridin-3-yl)oxy)picolinamide

HRID 520702

Reaction equation

HRID 520702 reaction equation
[OH:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9]([C:11]2[C:12](=[O:24])[N:13]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[N:14]([CH3:17])[C:15]=2[CH3:16])=[O:10])=[N:6][CH:7]=1.CC(C)([O-])C.[K+].Cl[C:32]1[CH:37]=[CH:36][N:35]=[C:34]([C:38]([NH2:40])=[O:39])[CH:33]=1>CN(C=O)C.O>[CH3:17][N:14]1[C:15]([CH3:16])=[C:11]([C:9]([NH:8][C:5]2[N:6]=[CH:7][C:2]([O:1][C:32]3[CH:37]=[CH:36][N:35]=[C:34]([C:38]([NH2:40])=[O:39])[CH:33]=3)=[CH:3][CH:4]=2)=[O:10])[C:12](=[O:24])[N:13]1[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

6

Reactant 3

HCID 3035434-Chloropyridine-2-carboxamideHCID 23665647Potassium tert-butoxideHCID 90033479HCID 90033479, compound

Product 1

HCID 730532664-((6-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamido)pyridin-3-yl)oxy)picolinamideYield 45.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of N-(5-hydroxypyridin-2-yl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (468 mg, 1.4 mmol) in DMF (30 mL) was added potassium tert-butoxide (486 mg, 4.33 mmol). The solution was stirred at rt for 20 minutes, followed by the addition of 4-chloropicolinamide (293 mg, 1.87 mmol). The reaction was heated at 120° C. for 2 hours, then cooled to rt, diluted with water (15 mL) and extracted with EtOAc (20 mL×3). The combined organic phases were washed with brine (20 mL) and concentrated in vacuo. The residue was purified by a silica column chromatography (DCM/MeOH (v/v)=50/1) to give the title compound as an off-white solid (285 mg, 44%).

Workup

  1. temperatureThe reaction was heated at 120° C. for 2 hours
  2. temperaturecooled to rt
  3. extractionextracted with EtOAc (20 mL×3)
  4. washThe combined organic phases were washed with brine (20 mL)
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by a silica column chromatography (DCM/MeOH (v/v)=50/1)

Sources & evidence

ORD record
ord-04c22a00f2ca4a76ab1dae17b8afcf67
Source dataset
uspto-grants-2016_05
Patent number
US09326975B2

Linked notes

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