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Acetamide → N-(4-((2-methyl-6-nitropyridin-3-yl)oxy)pyridin-2-yl)acetamide

HRID 2278927
Notes
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Reaction equation

HRID 2278927 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]([NH2:22])(=[O:21])[CH3:20].C([O-])([O-])=O.[Cs+].[Cs+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>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].CCOC(C)=O>[CH3:18][C:10]1[C:9]([O:8][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:22][C:19](=[O:21])[CH3:20])[CH:7]=2)=[CH:14][CH:13]=[C:12]([N+:15]([O-:17])=[O:16])[N:11]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 178AcetamideHCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 904036213-((2-Chloropyridin-4-yl)oxy)-2-methyl-6-nitropyridine

Product 1

HCID 90410470N-(4-((2-methyl-6-nitropyridin-3-yl)oxy)pyridin-2-yl)acetamideYield 24.4%

Reagents, catalysts & solvents

3
HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of Example A6 (1.7 g, 6.40 mmol) in dioxane (30 mL) was sparged with Ar, treated with acetamide (1.512 g, 25.6 mmol), Cs2CO3 (2.085 g, 6.40 mmol), X-Phos (0.153 g, 0.320 mmol) and Pd2(dba)3 (0.293 g, 0.320 mmol) and heated at 80° C. for 20 h. The mixture was cooled to RT, treated with EtOAc, the solids removed via filtration through diatomaceous earth and rinsed well with EtOAc. The filtrate was washed with water, then 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)acetamide (450 mg, 24%) as a light yellow solid. MS (ESI) m/z: 289.1 (M+H+).

Workup

  1. temperatureThe mixture was cooled to RT
  2. customthe solids removed via filtration through diatomaceous earth
  3. washrinsed well with EtOAc
  4. washThe filtrate was washed with water
  5. dry with materialbrine, dried over Na2SO4
  6. concentrationconcentrated to dryness
  7. custompurified via silica gel chromatography (EtOAc/DCM)

Sources & evidence

ORD record
ord-5398f9bdbe75478fb41ca4f8ac080acd
Source dataset
uspto-grants-2015_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09133183B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes