Dimethylacetamide → (S)-2-sec-Butylamino-6-cyano-isonicotinic acid methyl ester

HRID 732412Notes

Reaction equation

HRID 732412 reaction equation
[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8](Cl)[N:7]=[C:6]([NH:11][C@H:12]([CH2:14][CH3:15])[CH3:13])[CH:5]=1.[CH3:17][N:18](C)C(=O)C>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].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].[Zn].[Zn+2]>[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8]([C:17]#[N:18])[N:7]=[C:6]([NH:11][C@H:12]([CH2:14][CH3:15])[CH3:13])[CH:5]=1

Participants

7

Reactant 2

HCID 31374DimethylacetamideHCID 86614996HCID 86614996, compound

Product 1

HCID 68814564(S)-2-sec-Butylamino-6-cyano-isonicotinic acid methyl ester

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 32051Zinc(2+)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
130 °C

Procedure

Dissolve (S)-2-sec-butylamino-6-chloro-isonicotinic acid methyl ester (800 mg, 0.34 mmol), tris(dibenzylideneacetone)dipalladium (0) (120 mg, 0.13 mmol), 1,1′-bis(diphenylphosphino)ferrocene (146 mg, 0.26 mmol), zinc dust (52 mg) and zinc (II) cyamide (387 mg, 3.3 mmol) in N,N-dimethylacetamide (6.6 mL)) in a previously nitrogen-filled sealed vessel. Flush the reactants with nitrogen before sealing and heat for 6 h at 130° C. Cool to room temperature, dilute with ethyl acetate and wash with 2 N ammonium hydroxide. Wash the organic layer with saturated aqueous sodium chloride, dry (magnesium sulfate), concentrate and purify (silica gel chromatography, eluting with 0:100 to 05:95 ethyl acetate:hexanes) to give the title compound.

Workup

  1. additionfilled
  2. customsealed vessel
  3. customFlush the reactants with nitrogen
  4. temperatureCool to room temperature
  5. additiondilute with ethyl acetate
  6. washwash with 2 N ammonium hydroxide
  7. washWash the organic layer with saturated aqueous sodium chloride
  8. dry with materialdry (magnesium sulfate)
  9. concentrationconcentrate
  10. custompurify
  11. wash(silica gel chromatography, eluting with 0:100 to 05:95 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-9051a647cf194c9eb07fae7a57bc0fb2
Source dataset
uspto-grants-2009_09
Patent number
US07585885B2

Reaction notes

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