Acetamide → HCID 90425939, compound

HRID 2278906Notes

Reaction equation

HRID 2278906 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:10]([CH3:17])=[N:11][C:12](I)=[CH:13][C:14]=2[CH3:15])[CH:5]=[CH:4][N:3]=1.[C:18]([NH2:21])(=[O:20])[CH3:19].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>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:14]([CH3:15])=[CH:13][C:12]([NH:21][C:18](=[O:20])[CH3:19])=[N:11][C:10]=2[CH3:17])[CH:5]=[CH:4][N:3]=1

Participants

7

Reactant 3

HCID 178AcetamideHCID 10796Cesium carbonateHCID 90425921HCID 90425921, compound

Product 1

HCID 90425939HCID 90425939, compoundYield 51%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 3-((2-chloropyridin-4-yl)oxy)-6-iodo-2,4-dimethylpyridine (1.45 g, 4.02 mmol), acetamide (950 mg, 16.09 mmol), Cs2CO3 (1.965 g, 6.03 mmol) and X-phos (96 mg, 0.201 mmol) in dioxane (25 mL) was sparged with Ar, treated with Pd2(dba)3 (184 mg, 0.201 mmol), sparged again with Ar and heated at 85° C. overnight. The mixture was cooled to RT, diluted with EtOAc and the solids removed via filtration through diatomaceous earth. The filtrate was washed with water, then brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (EtOAc/Hex) to afford N-(5-((2-chloropyridin-4-yl)oxy)-4,6-dimethylpyridin-2-yl)acetamide (598 mg, 51%). 1H NMR (400 MHz, DMSO-d6): δ 10.53 (s, 1 H), 8.26 (d, J=5.8 Hz, 1 H), 7.94 (s, 1 H), 6.99 (d, J=2.3 Hz, 1 H), 6.85 (dd, J=5.8, 2.3 Hz, 1 H), 2.17 (s, 3 H), 2.06 (d, J=1.7 Hz, 6 H); MS (ESI) m/z: 292.1 (M+H+).

Workup

  1. customwas sparged with Ar
  2. customsparged again with Ar
  3. temperatureThe mixture was cooled to RT
  4. additiondiluted with EtOAc
  5. customthe solids removed via filtration through diatomaceous earth
  6. washThe filtrate was washed with water
  7. dry with materialbrine, dried over Na2SO4
  8. concentrationconcentrated to dryness
  9. custompurified via silica gel chromatography (EtOAc/Hex)

Sources & evidence

ORD record
ord-501fcc32e2804cd0bf57ac406c694ec2
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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