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

HRID 732444Notes

Reaction equation

HRID 732444 reaction equation
[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8](Cl)[N:7]=[C:6]([NH:11][CH: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]>[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

6

Reactant 2

HCID 31374DimethylacetamideHCID 866150062-Sec-butylamino-6-chloro-isonicotinic acid methyl ester

Product 1

HCID 68814564(S)-2-sec-Butylamino-6-cyano-isonicotinic acid methyl esterYield 59%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalyst2×HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
120 °C

Procedure

Add 2-sec-butylamino-6-chloro-isonicotinic acid methyl ester (1.22 g, 5.0 mmol), tris(dibenzylideneacetone)dipalladium (183 mg, 0.2 mmol), 1,1′-bis(diphenylphosphino)ferrocene (222 mg, 0.4 mmol), zinc cyamide (587 mg, 5.0 mmol), and zinc dust (78 mg, 1.2 mmol) in N,N-dimethylacetamide (10 mL) and heat in a sealed tube at 120° C. overnight. Cool to room temperature, filter through a filtering agent, concentrate and purify (silica gel chromatography, eluting with 10:90 to 15:85 ethyl acetate:hexanes) to give the title compound (703 mg, 59%).

Workup

  1. temperatureCool to room temperature
  2. filtrationfilter through a filtering agent
  3. concentrationconcentrate
  4. custompurify
  5. wash(silica gel chromatography, eluting with 10:90 to 15:85 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-0440af9361934182a14386a1ef841615
Source dataset
uspto-grants-2009_09
Patent number
US07585885B2

Reaction notes

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