Cesium carbonate → 1,1-Dimethyl-3-(4-((6-nitropyridin-3-yl)oxy)pyridin-2-yl)urea

HRID 626508

Reaction equation

Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[N:11][C:12]([N+:15]([O-:17])=[O:16])=[CH:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.[CH3:18][N:19]([CH3:23])[C:20]([NH2:22])=[O:21].C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].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]>[CH3:18][N:19]([CH3:23])[C:20]([NH:22][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[N:11][C:12]([N+:15]([O-:17])=[O:16])=[CH:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1)=[O:21]

Participants

Conditions

Temperature: 95 °C

Procedure

A mixture of Example A1 (1 g, 3.97 mmol) in dioxane (20 mL) was sparged with Ar, treated with N,N-dimethyl urea (0.700 g, 7.95 mmol) and Cs2CO3 (1.942 g, 5.96 mmol), sparged with Ar, treated with dppf [1,1′-bis(diphenylphosphino)ferrocene] (12.38 g, 22.33 mmol) and Pd2(dba)3 (0.182 g, 0.199 mmol), sparged once again with Ar and heated at 95° C. overnight. The mixture was cooled to RT, treated with EtOAc and the solids removed via filtration through silica gel. The filtrate was concentrated to dryness and purified twice via silica gel chromatography (MeOH/DCM) to afford 1,1-dimethyl-3-(4-((6-nitropyridin-3-yl)oxy)pyridin-2-yl)urea (616 mg, 51%). MS (ESI) m/z: 304.1 (M+H+).

Workup

customsparged with Ar
customsparged once again with Ar
temperatureThe mixture was cooled to RT
additiontreated with EtOAc
customthe solids removed via filtration through silica gel
concentrationThe filtrate was concentrated to dryness
custompurified twice via silica gel chromatography (MeOH/DCM)

Sources & evidence

ORD record: ord-3201dcc5150d41e88ce9e0c5933e6f3e
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09309224B2

Linked notes

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