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

HRID 626510Notes

Reaction equation

HRID 626510 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+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>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]>[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

7

Reactant 4

HCID 10796Cesium carbonateHCID 11737N,N-DimethylureaHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 593227792-Chloro-4-((6-nitropyridin-3-yl)oxy)pyridine

Product 1

HCID 904108451,1-Dimethyl-3-(4-((6-nitropyridin-3-yl)oxy)pyridin-2-yl)ureaYield 86.2%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of Example A1 (6 g, 23.8 mmol) in dioxane (100 mL) was sparged with Ar under sonication for 20 min, then treated with N,N-dimethyl urea (10.50 g, 119 mmol), Cs2CO3 (1.942 g, 5.96 mmol), and XANTPHOS (2.76 g, 4.77 mmol), and again sparged with Ar under sonication for 15 min. Pd2(dba)3 (2.18 g, 2.38 mmol) was added and the mixture was again sparged with Ar for 15 min under sonication. The reaction was then heated to 100° C. for 3 h. The mixture was cooled to RT, diluted with EtOAc and the solids removed via filtration through diatomaceous earth. The filtrate was concentrated to dryness and purified by silica gel chromatography (MeOH/DCM) to afford 1,1-dimethyl-3-(4-((6-nitropyridin-3-yl)oxy)pyridin-2-yl)urea (6.22 g, 81%). MS (ESI) m/z: 304.1 (M+H+).

Workup

  1. customagain sparged with Ar under sonication for 15 min
  2. customthe mixture was again sparged with Ar for 15 min under sonication
  3. temperatureThe mixture was cooled to RT
  4. additiondiluted with EtOAc
  5. customthe solids removed via filtration through diatomaceous earth
  6. concentrationThe filtrate was concentrated to dryness
  7. custompurified by silica gel chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-514a175f3c754f9c80a7ea72e5e2c717
Source dataset
uspto-grants-2016_04
Patent number
US09309224B2

Reaction notes

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