Cesium carbonate → Methyl 2-(6-methoxy-3-pyridinyl)aminonicotinate

HRID 2194535Notes

Reaction equation

HRID 2194535 reaction equation
Cl[C:2]1[N:11]=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[CH3:12][O:13][C:14]1[N:19]=[CH:18][C:17]([NH2:20])=[CH:16][CH:15]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:12][O:13][C:14]1[N:19]=[CH:18][C:17]([NH:20][C:2]2[N:11]=[CH:10][CH:9]=[CH:8][C:3]=2[C:4]([O:6][CH3:7])=[O:5])=[CH:16][CH:15]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 811216-Methoxy-3-pyridinylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 819931Methyl 2-chloronicotinate

Product 1

HCID 67009514Methyl 2-(6-methoxy-3-pyridinyl)aminonicotinateYield 90.4%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

5.0 g (29 mmol) of methyl 2-chloronicotinate and 4.3 g (35 mmol) of 6-methoxypyridine-3-amine were dissolved in toluene (80 mL), and 16.1 g (50 mmol) of cesium carbonate, 1.3 g (1.5 mmol) of tris(dibenzylideneacetone)dipalladium(0), and 1.8 g (3.1 mmol) of 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene were added to the solution. The resulting mixture was heated and stirred for 72 hours at 90° C. The solvent was distilled off from the reaction mixture, water and ethyl acetate were added to the residue, and the mixture was filtered. The filtrate was extracted with ethyl acetate, and the organic phase was dried and concentrated. The residue was purified by column chromatography (ethyl acetate:n-hexane=1:4 to 1:1), and thus 6.8 g of the title compound was obtained as a pale yellow viscous product (yield: 96%).

Workup

  1. temperatureThe resulting mixture was heated
  2. distillationThe solvent was distilled off from the reaction mixture, water and ethyl acetate
  3. additionwere added to the residue
  4. filtrationthe mixture was filtered
  5. extractionThe filtrate was extracted with ethyl acetate
  6. customthe organic phase was dried
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography (ethyl acetate:n-hexane=1:4 to 1:1)

Sources & evidence

ORD record
ord-87a163921ec44ad6839b1ad684b19153
Source dataset
uspto-grants-2012_12
Patent number
US08334236B2

Reaction notes

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