Acetamide → N-(5-((2-chloropyridin-4-yl)oxy)pyrazin-2-yl)acetamide

HRID 1049275Notes

Reaction equation

Br[C:2]1[CH:7]=[N:6][C:5]([O:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]([Cl:15])[CH:10]=2)=[CH:4][N:3]=1.[C:16]([NH2:19])(=[O:18])[CH3:17].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]>[Cl:15][C:11]1[CH:10]=[C:9]([O:8][C:5]2[N:6]=[CH:7][C:2]([NH:19][C:16](=[O:18])[CH3:17])=[N:3][CH:4]=2)[CH:14]=[CH:13][N:12]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of 2-bromo-5-((2-chloropyridin-4-yl)oxy)pyrazine (1.2 g, 4.19 mmol) in dioxane (20 mL) was degassed, treated with acetamide (0.495 g, 8.38 mmol), Cs2CO3 (2.05 g, 6.28 mmol), X-Phos (0.200 g, 0.419 mmol) and Pd2(dba)3 (0.192 g, 0.209 mmol) and heated at 80° C. for 3 h. The mixture was cooled to RT and diluted with EtOAc. The solids were removed via filtration through diatomaceous earth, rinsed well with EtOAc, and the filtrate washed with H2O, 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)pyrazin-2-yl)acetamide (0.35 g, 31%). MS (ESI) m/z: 265.0 (M+H+).

Workup

temperatureThe mixture was cooled to RT
customThe solids were removed via filtration through diatomaceous earth
washrinsed well with EtOAc
washthe filtrate washed with H2O
dry with materialbrine, dried over Na2SO4
concentrationconcentrated to dryness
custompurified via silica gel chromatography (EtOAc/Hex)

Sources & evidence

ORD record: ord-22f928b61019412b88df179c57b29d2b
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09382228B2

Reaction notes

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