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

HRID 718142Notes

Reaction equation

HRID 718142 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:10]([CH3:18])=[CH:11][C:12]([N+:15]([O-:17])=[O:16])=[N: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.CCOC(C)=O.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]>[CH3:18][C:10]1[CH:11]=[C:12]([N+:15]([O-:17])=[O:16])[N:13]=[CH:14][C:9]=1[O:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:22][C:19](=[O:21])[CH3:20])[CH:7]=1

Participants

8

Reactant 4

HCID 178AcetamideHCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 866416892-Chloro-4-(4-methyl-6-nitropyridin-3-yloxy)pyridine

Product 1

HCID 90409722N-(4-((4-methyl-6-nitropyridin-3-yl)oxy)pyridin-2-yl)acetamideYield 64%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
90 °C

Procedure

A solution of 5-((2-chloropyridin-4-yl)oxy)-4-methyl-2-nitropyridine (0.52 g, 1.957 mmol; See: Example A9) in dioxane (15 mL) was sparged with Ar, treated with acetamide (0.347 g, 5.87 mmol), Cs2CO3 (0.638 g, 1.957 mmol), X-Phos (0.093 g, 0.196 mmol) and Pd2(dba)3 (0.179 g, 0.196 mmol) and heated at 90° C. overnight. The mixture was cooled to RT, diluted with EtOAc, the solids removed via filtration through diatomaceous earth, washed with EtOAc and 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-((4-methyl-6-nitropyridin-3-yl)oxy)pyridin-2-yl)acetamide (360 mg, 64%). 1H NMR (400 MHz, DMSO-d6): δ 10.66 (s, 1H), 8.47 (s, 1H), 8.43 (s, 1H), 8.24 (d, J=5.7 Hz, 1H), 7.72 (d, J=2.4 Hz, 1H), 6.74 (dd, J=5.7, 2.4 Hz, 1H), 2.33 (s, 3H), 2.05 (s, 3H); 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. washwashed 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-d783d6b483874f98af5905a7abb99ab9
Source dataset
uspto-grants-2015_11
Patent number
US09193719B2

Reaction notes

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