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

HRID 626499Notes

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

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of Example A3 (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

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

Sources & evidence

ORD record: ord-b53558f2d76d4cf68df19e77f6d1ce44
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09309224B2

Reaction notes

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