Acetamide → N-(5-((2-chloropyridin-4-yl)oxy)-6-methylpyridin-2-yl)acetamide

HRID 2278888Notes

Reaction equation

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

Participants

Conditions

Temperature: 83 °C

Procedure

A solution of 3-((2-chloropyridin-4-yl)oxy)-6-iodo-2-methylpyridine (8.5 g, 24.53 mmol) in dioxane (100 mL) was sparged with argon, treated with acetamide (5.07 g, 86 mmol), Cs2CO3 (11.99 g, 36.8 mmol), X-Phos (0.585 g, 1.226 mmol) and Pd2(dba)3 (1.123 g, 1.226 mmol) and heated at 83° C. for 16 h. The mixture was cooled to RT, treated with EtOAc, solids 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)-6-methylpyridin-2-yl)acetamide (3.8 g, 56%) as an off-white solid. MS (ESI) m/z: 278.0 (M+H+).

Workup

temperatureThe mixture was cooled to RT
customremoved 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-fe0fb6680e254d14bc63c8b7d15a922d
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09133183B2

Reaction notes

Loading…