Triethylamine → N-(4-((2-(cyclobutanecarboxamido)pyridin-4-yl)oxy)phenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide

HRID 520723Notes

Reaction equation

HRID 520723 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]([C:18]3[C:19](=[O:31])[N:20]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[N:21]([CH3:24])[C:22]=3[CH3:23])=[O:17])=[CH:11][CH:10]=2)[CH:5]=[CH:4][N:3]=1.CCN(CC)CC.[CH:39]1([C:43](Cl)=[O:44])[CH2:42][CH2:41][CH2:40]1>C1COCC1.CN(C=O)C.C1COCC1.CCOC(C)=O>[CH:39]1([C:43]([NH:1][C:2]2[CH:7]=[C:6]([O:8][C:9]3[CH:10]=[CH:11][C:12]([NH:15][C:16]([C:18]4[C:19](=[O:31])[N:20]([C:25]5[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=5)[N:21]([CH3:24])[C:22]=4[CH3:23])=[O:17])=[CH:13][CH:14]=3)[CH:5]=[CH:4][N:3]=2)=[O:44])[CH2:42][CH2:41][CH2:40]1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 78705Cyclobutanecarbonyl chlorideHCID 73053608N-(4-((2-aminopyridin-4-yl)oxy)phenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide

Product 1

HCID 73051230N-(4-((2-(cyclobutanecarboxamido)pyridin-4-yl)oxy)phenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamideYield 25%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of N-(4-((2-aminopyridin-4-yl)oxy)phenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (100 mg, 0.241 mmol) in THF/DMF (15 mL/1 mL) was added Et3N (0.06 mL, 0.482 mmol). The suspension was cooled to 0° C., then a solution of cyclobutanecarbonyl chloride (31.0 mg, 0.265 mmol) in THF (5 mL) was added to the reaction system drop wise over 1 hour. The reaction was stirred at rt for 5 hours, and then diluted with EtOAc (20 mL). The resulted mixture was washed with water (25 mL×3), followed by washing with brine (25 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by a silica gel column chromatography (DCM/EtOAc/MeOH (v/v)=100/25/1) to give the title compound as a white solid (30 mg, 25%).

Workup

  1. washThe resulted mixture was washed with water (25 mL×3)
  2. washby washing with brine (25 mL)
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by a silica gel column chromatography (DCM/EtOAc/MeOH (v/v)=100/25/1)

Sources & evidence

ORD record
ord-08d7f965156c49d8aed2112bbb05452e
Source dataset
uspto-grants-2016_05
Patent number
US09326975B2

Reaction notes

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