Propionamide → N-(4-((2-methyl-6-nitropyridin-3-yl)oxy)pyridin-2-yl)propionamide

HRID 626502Notes

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]([NH2:23])(=[O:22])[CH2:20][CH3:21].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>[CH3:18][C:10]1[C:9]([O:8][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:23][C:19](=[O:22])[CH2:20][CH3:21])[CH:7]=2)=[CH:14][CH:13]=[C:12]([N+:15]([O-:17])=[O:16])[N:11]=1

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of Example A3 (0.50 g, 1.882 mmol), propionamide (0.550 g, 7.53 mmol), Cs2CO3 (0.920 g, 2.82 mmol), and X-phos (0.045 g, 0.094 mmol) in dioxane (10 mL) was sparged with Ar, treated with Pd2(dba)3 (0.086 g, 0.094 mmol), sparged again with Ar and heated at 90° C. for 20 h. The mixture was cooled to RT, treated with EtOAc and the solids removed via filtration. The filtrate was washed with 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)propionamide (420 mg, 74%). MS (ESI) m/z: 303.1 (M+H+).

Workup

customsparged again with Ar
temperatureThe mixture was cooled to RT
additiontreated with EtOAc
customthe solids removed via filtration
washThe filtrate was washed with brine
dry with materialdried over Na2SO4
concentrationconcentrated to dryness
custompurified via silica gel chromatography (EtOAc/DCM)

Sources & evidence

ORD record: ord-0ff586d31f0a4a8195adc8d348eaf4a4
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09309224B2

Reaction notes

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