3,4-Dichloropyridine-2-carboxamide → 3-chloro-4-(4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamido)-2,5-difluorophenoxy)picolinamide

HRID 520674Notes

Reaction equation

HRID 520674 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([OH:8])[C:5]([F:9])=[CH:4][C:3]=1[NH:10][C:11]([C:13]1[C:14](=[O:26])[N:15]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:16]([CH3:19])[C:17]=1[CH3:18])=[O:12].CC([O-])(C)C.[K+].[Cl:33][C:34]1[C:35]([C:41]([NH2:43])=[O:42])=[N:36][CH:37]=[CH:38][C:39]=1Cl>CN(C=O)C>[Cl:33][C:34]1[C:35]([C:41]([NH2:43])=[O:42])=[N:36][CH:37]=[CH:38][C:39]=1[O:8][C:6]1[CH:7]=[C:2]([F:1])[C:3]([NH:10][C:11]([C:13]2[C:14](=[O:26])[N:15]([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[N:16]([CH3:19])[C:17]=2[CH3:18])=[O:12])=[CH:4][C:5]=1[F:9]

Participants

5

Reactant 3

HCID 231651433,4-Dichloropyridine-2-carboxamideHCID 23665647Potassium tert-butoxideHCID 90033342N-(2,5-difluoro-4-hydroxyphenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide

Product 1

HCID 730509243-chloro-4-(4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamido)-2,5-difluorophenoxy)picolinamideYield 60.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of N-(2,5-difluoro-4-hydroxyphenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (395 mg, 1.1 mmol) in DMF (5.0 mL) was added t-BuOK (202 mg, 1.8 mmol) and the mixture was stirred at rt for 30 minutes. Then 3,4-dichloropicolinamide (190 mg, 1.0 mmol) was added and the mixture was microwaved at 120° C. for 2 hours, then cooled to rt, quenched with water (30 mL) and extracted with EtOAc (50 mL×3). The combined organic phases were washed with brine (50 mL×3), dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by a silica gel column chromatography (MeOH/DCM (v/v)=1/30) to give the title compound as a pale yellow solid (310 mg, 60%).

Workup

  1. customthe mixture was microwaved at 120° C. for 2 hours
  2. temperaturecooled to rt
  3. customquenched with water (30 mL)
  4. extractionextracted with EtOAc (50 mL×3)
  5. washThe combined organic phases were washed with brine (50 mL×3)
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by a silica gel column chromatography (MeOH/DCM (v/v)=1/30)

Sources & evidence

ORD record
ord-3e19e3ae62ce40f5987a88fde83edb8b
Source dataset
uspto-grants-2016_05
Patent number
US09326975B2

Reaction notes

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