N-methyl-2-pyrrolidone → HCID 69003486, compound

HRID 2102421Notes

Reaction equation

HRID 2102421 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:10]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[F:18])=[C:9]([F:19])[C:8]([Cl:20])=[C:7](Cl)[N:6]=1)=[O:4].[CH3:22][N:23]1C(=O)CCC1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[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].[C-]#N.[C-]#N.[Zn+2]>[CH3:1][O:2][C:3]([C:5]1[C:10]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[F:18])=[C:9]([F:19])[C:8]([Cl:20])=[C:7]([C:22]#[N:23])[N:6]=1)=[O:4]

Participants

6

Reactant 2

HCID 13387N-methyl-2-pyrrolidoneHCID 86599611HCID 86599611, compound

Product 1

HCID 69003486HCID 69003486, compound

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
120 °C

Procedure

A mixture of 5,6-dichloro-4-fluoro-3-(2-fluorophenylamino)-pyridine-2-carboxylic acid methyl ester (1.00 equivalent) (prepared in Example 8), dppf (0.02 equivalents), Pd2dba3 (0.01 equivalents), and Zn(CN)2 (0.60 equivalents) in NMP is stirred at 120° C. in a sealed tube. After stirring for 20 hours, the reaction mixture is cooled to room temperature and quenched with a 4:1:4 (volume) mixture solution of saturated aqueous NH4Cl-conc NH4OH-water. The mixture is extracted with EtOAc. The organic layer is washed with saturated aqueous NH4Cl/conc. NH4OH/water, and brine. The organic layer is dried over MgSO4, filtered, and concentrated in vacuo to give the crude material that is purified by flash column chromatography to afford the desired product.

Workup

  1. stirringAfter stirring for 20 hours
  2. temperaturethe reaction mixture is cooled to room temperature
  3. customquenched with a 4:1:4 (volume) mixture solution of saturated aqueous NH4Cl-conc NH4OH-water
  4. extractionThe mixture is extracted with EtOAc
  5. washThe organic layer is washed with saturated aqueous NH4Cl/conc
  6. dry with materialThe organic layer is dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give the crude material that
  10. customis purified by flash column chromatography

Sources & evidence

ORD record
ord-d246b5925f8e412ab0a6b599f7ca623c
Source dataset
uspto-grants-2009_08
Patent number
US07576072B2

Reaction notes

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