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

HRID 870463Notes

Reaction equation

HRID 870463 reaction equation
[Cl:1][C:2]1[C:3](C(N)=O)=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]([C:18]2[C:19](=[O:31])[N:20]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[N:21]([CH3:24])[C:22]=2[CH3:23])=[O:17])=[C:11]([F:32])[CH:10]=1.C(OI(C1C=CC=CC=1)OC(=O)C)(=O)C.CC#[N:53]>CCOC(C)=O.O>[NH2:53][C:3]1[C:2]([Cl:1])=[C:7]([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:26]=[CH:27][CH:28]=[CH:29][CH:30]=4)[N:21]([CH3:24])[C:22]=3[CH3:23])=[O:17])=[C:11]([F:32])[CH:10]=2)[CH:6]=[CH:5][N:4]=1

Participants

6

Reactant 3

HCID 6342AcetonitrileHCID 76724Iodobenzene diacetateHCID 730510753-chloro-4-(4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamido)-3-fluorophenoxy)picolinamide

Product 1

HCID 73053651N-(4-((2-amino-3-chloropyridin-4-yl)oxy)-2-fluorophenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamideYield 47%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of 3-chloro-4-(4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamido)-3-fluorophenoxy)picolinamide (379 mg, 0.764 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, then PhI(OAc)2 (295 mg, 0.917 mmol) was added and the mixture was stirred for another 30 minutes at 0° C., then allowed to warmed up to rt and stirred for another 10 hours. 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 gel column chromatography (CH2Cl2/MeOH (v/v)=50/1) to give the title compound as a yellow solid (150 mg, 47.0%).

Workup

  1. temperaturewas cooled
  2. stirringthe mixture was stirred for another 30 minutes at 0° C.
  3. temperatureto warmed up to rt
  4. stirringstirred for another 10 hours
  5. filtrationFiltered
  6. washthe filter cake was washed with EtOAc (5 mL)
  7. concentrationThe filtrate was concentrated in vacuo
  8. customthe residue was purified by a silica gel column chromatography (CH2Cl2/MeOH (v/v)=50/1)

Sources & evidence

ORD record
ord-f5762c6ef80c45e78fbc2d436c77bf20
Source dataset
uspto-grants-2015_03
Patent number
US08969388B1

Reaction notes

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