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

HRID 520680Notes

Reaction equation

HRID 520680 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[CH:11][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])=[N:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.[CH:32]1([C:35](Cl)=[O:36])[CH2:34][CH2:33]1>C(Cl)Cl.C(N(CC)CC)C.O>[CH:32]1([C:35]([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])=[N:13][CH:14]=3)[CH:5]=[CH:4][N:3]=2)=[O:36])[CH2:34][CH2:33]1

Participants

6

Reactant 2

HCID 77637Cyclopropanecarbonyl chlorideHCID 73053627N-(5-((2-aminopyridin-4-yl)oxy)pyridin-2-yl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide

Product 1

HCID 91825555N-(5-((2-(cyclopropanecarboxamido)pyridin-4-yl)oxy)pyridin-2-yl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamideYield 60.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

To a suspension of N-(5-((2-aminopyridin-4-yl)oxy)pyridin-2-yl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (500 mg, 1.2 mmol) in DCM (5 mL) and triethylamine (1 mL) was added cyclopropanecarbonyl chloride (377 mg, 3.6 mmol) at 0° C. slowly. The mixture was warmed up to rt and stirred for 4.5 hours, then diluted with DCM (10 mL) and water (10 mL). The organic phase was separated and concentrated in vacuo. The residue was dissolved in MeOH (30 mL), and saturated solution of Na2CO3 (30 mL). The resulted mixture was stirred at rt for 2 hours, then filtered and the filtrate was concentrated in vacuo. The residue was purified by a silica gel column chromatography (DCM/MeOH (v/v)=50/1) to give the title compound as an off-white solid (350 mg, 60%).

Workup

  1. customThe organic phase was separated
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was dissolved in MeOH (30 mL)
  4. stirringThe resulted mixture was stirred at rt for 2 hours
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated in vacuo
  7. customThe residue was purified by a silica gel column chromatography (DCM/MeOH (v/v)=50/1)

Sources & evidence

ORD record
ord-797e97b8d24140189ecb917ff1b164c4
Source dataset
uspto-grants-2016_05
Patent number
US09326975B2

Reaction notes

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