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

HRID 520685Notes

Reaction equation

HRID 520685 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][C:10]=2[F:32])[CH:5]=[CH:4][N:3]=1.CCN(CC)CC.[CH:40]1([C:43](Cl)=[O:44])[CH2:42][CH2:41]1.C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl.O>[CH:40]1([C:43]([NH:1][C:2]2[CH:7]=[C:6]([O:8][C:9]3[CH:14]=[CH:13][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:11][C:10]=3[F:32])[CH:5]=[CH:4][N:3]=2)=[O:44])[CH2:42][CH2:41]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 77637Cyclopropanecarbonyl chlorideHCID 73053650N-(4-((2-aminopyridin-4-yl)oxy)-3-fluorophenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-c arboxamide

Product 1

HCID 72734375N-(4-((2-(cyclopropanecarboxamido)pyridin-4-yl)oxy)-3-fluorophenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamideYield 63.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of N-(4-((2-aminopyridin-4-yl)oxy)-3-fluorophenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (217 mg, 0.5 mmol) in DCM (5 mL) was added Et3N (253 mg, 2.5 mmol) and cyclopropanecarbonyl chloride (125 mg, 1.2 mmol) at 0° C. The reaction mixture was stirred at rt for 4 hours, quenched with H2O (10 mL) and extracted with DCM (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 dissolved in CH3OH (20 mL), and a solution of Na2CO3 (106 mg, 1.0 mmol) in H2O (1 mL). The resulted mixture was stirred at rt for 1 hour and concentrated in vacuo. The residue was purified by a silica gel column chromatography (pure DCM) to give the title compound as a beige solid (158 mg, 63.2%).

Workup

  1. customquenched with H2O (10 mL)
  2. extractionextracted with DCM (50 mL×3)
  3. washThe combined organic phases were washed with brine (50 mL×3)
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in CH3OH (20 mL)
  7. stirringThe resulted mixture was stirred at rt for 1 hour
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by a silica gel column chromatography (pure DCM)

Sources & evidence

ORD record
ord-510d386ac3484868810a544a5163974a
Source dataset
uspto-grants-2016_05
Patent number
US09326975B2

Reaction notes

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