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

HRID 870461Notes

Reaction equation

HRID 870461 reaction equation
[CH3:1][N:2]1[C:6]([CH3:7])=[C:5]([C:8]([NH:10][C:11]2[CH:26]=[CH:25][C:14]([O:15][C:16]3[CH:21]=[CH:20][N:19]=[C:18](C(N)=O)[CH:17]=3)=[CH:13][C:12]=2[F:27])=[O:9])[C:4](=[O:28])[N:3]1[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.CC#[N:37].O.C(OI(C1C=CC=CC=1)OC(=O)C)(=O)C>CCOC(C)=O>[NH2:37][C:18]1[CH:17]=[C:16]([O:15][C:14]2[CH:25]=[CH:26][C:11]([NH:10][C:8]([C:5]3[C:4](=[O:28])[N:3]([C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=4)[N:2]([CH3:1])[C:6]=3[CH3:7])=[O:9])=[C:12]([F:27])[CH:13]=2)[CH:21]=[CH:20][N:19]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6342AcetonitrileHCID 76724Iodobenzene diacetateHCID 730510744-(4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamido)-3-fluorophenoxy)picolinamide

Product 1

HCID 73053631N-(4-((2-aminopyridin-4-yl)oxy)-2-fluorophenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamideYield 17.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 4-(4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamido)-3-fluorophenoxy)picolinamide (370 mg (a little wet), 0.746 mmol) in EtOAc (4.5 mL), CH3CN (4.5 mL) and H2O (2.5 mL) was cooled and stirred at 0° C. for 30 minutes and then PhI(OAc)2 (288 mg, 0.895 mmol) was added. The resulted mixture was stirred at 0° C. for another 30 minutes, then warmed up to rt and stirred for 7 hours. The mixture was filtered and the filter cake was washed with EtOAc (5 mL). The filtrate was concentrated in vacuo and the residue was purified by a silica column gel chromatography (CH2Cl2/MeOH (v/v)=250/9), followed by purifying again by silica gel column chromatography (CH2Cl2/MeOH (v/v)=50/1) to give the title compound as a beige white solid (46 mg, 17.3%).

Workup

  1. stirringThe resulted mixture was stirred at 0° C. for another 30 minutes
  2. temperaturewarmed up to rt
  3. stirringstirred for 7 hours
  4. filtrationThe mixture was filtered
  5. washthe filter cake was washed with EtOAc (5 mL)
  6. concentrationThe filtrate was concentrated in vacuo
  7. customthe residue was purified by a silica column gel chromatography (CH2Cl2/MeOH (v/v)=250/9)
  8. customby purifying again by silica gel column chromatography (CH2Cl2/MeOH (v/v)=50/1)

Sources & evidence

ORD record
ord-d9c223a1e6b34f0c921583b9ddf3e90f
Source dataset
uspto-grants-2015_03
Patent number
US08969388B1

Reaction notes

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