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Propionamide → N-(4-((2-methyl-6-nitropyridin-3-yl)oxy)pyridin-2-yl)propionamide

HRID 626502
Notes
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Reaction equation

HRID 626502 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:10]([CH3:18])=[N:11][C:12]([N+:15]([O-:17])=[O:16])=[CH:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.[C:19]([NH2:23])(=[O:22])[CH2:20][CH3:21].C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>[CH3:18][C:10]1[C:9]([O:8][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:23][C:19](=[O:22])[CH2:20][CH3:21])[CH:7]=2)=[CH:14][CH:13]=[C:12]([N+:15]([O-:17])=[O:16])[N:11]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 3

HCID 6578PropionamideHCID 10796Cesium carbonateHCID 904036213-((2-Chloropyridin-4-yl)oxy)-2-methyl-6-nitropyridine

Product 1

HCID 90410285N-(4-((2-methyl-6-nitropyridin-3-yl)oxy)pyridin-2-yl)propionamideYield 74%

Reagents, catalysts & solvents 3

HCID 9811564
Bis(dibenzylideneacetone)palladium
Catalyst
HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalyst
HCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of Example A3 (0.50 g, 1.882 mmol), propionamide (0.550 g, 7.53 mmol), Cs2CO3 (0.920 g, 2.82 mmol), and X-phos (0.045 g, 0.094 mmol) in dioxane (10 mL) was sparged with Ar, treated with Pd2(dba)3 (0.086 g, 0.094 mmol), sparged again with Ar and heated at 90° C. for 20 h. The mixture was cooled to RT, treated with EtOAc and the solids removed via filtration. The filtrate was washed with brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (EtOAc/DCM) to afford N-(4-((2-methyl-6-nitropyridin-3-yl)oxy)pyridin-2-yl)propionamide (420 mg, 74%). MS (ESI) m/z: 303.1 (M+H+).

Workup

  1. customsparged again with Ar
  2. temperatureThe mixture was cooled to RT
  3. additiontreated with EtOAc
  4. customthe solids removed via filtration
  5. washThe filtrate was washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated to dryness
  8. custompurified via silica gel chromatography (EtOAc/DCM)

Sources & evidence

ORD record
ord-0ff586d31f0a4a8195adc8d348eaf4a4
Source dataset
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09309224B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes