Pyridine → N4-[4-(tert-Butyl)-1,3-thiazol-2-yl]-2-(acetylamino)isonicotinamide

HRID 1828440Notes

Reaction equation

HRID 1828440 reaction equation
[C:1]([NH:4][C:5]1[CH:6]=[C:7]([CH:11]=[CH:12][N:13]=1)[C:8]([OH:10])=O)(=[O:3])[CH3:2].S(Cl)(Cl)=O.N1C=CC=CC=1.[C:24]([C:28]1[N:29]=[C:30]([NH2:33])[S:31][CH:32]=1)([CH3:27])([CH3:26])[CH3:25]>O.ClCCl>[C:24]([C:28]1[N:29]=[C:30]([NH:33][C:8](=[O:10])[C:7]2[CH:11]=[CH:12][N:13]=[C:5]([NH:4][C:1](=[O:3])[CH3:2])[CH:6]=2)[S:31][CH:32]=1)([CH3:27])([CH3:26])[CH3:25]

Participants

7

Reactant 4

HCID 1049PyridineHCID 24386Thionyl ChlorideHCID 27342024-tert-Butyl-1,3-thiazol-2-amineHCID 37744662-Acetamidopyridine-4-carboxylic acid

Product 1

HCID 22063745N4-[4-(tert-Butyl)-1,3-thiazol-2-yl]-2-(acetylamino)isonicotinamideYield 61.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

2-(Acetylamino)isonicotinic acid (500 mg, 2.8 mmol) was added dropwise with thionyl chloride (15 ml, 68.5 mmol) at room temperature, warmed to 80° C. and stirred for 30 minutes. The reaction solution was returned to room temperature, concentrated under reduced pressure, and the residue was subjected to azeotropy with toluene to evaporate excessive thionyl chloride. The resulting yellow crystals was added to a mixed solution of pyridine (0.25 ml), dichloromethane (5 ml) and 4-(tert-butyl)-1,3-thiazol-2-amine (525 mg, 3.35 mmol) under ice cooling. The mixture was stirred at 0° C. for 30 minutes, then warmed to room temperature, and further stirred for 2 hours and 30 minutes. The reaction solution was added with water and extracted with chloroform. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform→chloroform:methanol=80:1→50:1) to obtain 545.8 mg (61%) of the title compound.

Workup

  1. customwas returned to room temperature
  2. concentrationconcentrated under reduced pressure
  3. customto evaporate excessive thionyl chloride
  4. stirringThe mixture was stirred at 0° C. for 30 minutes
  5. temperaturewarmed to room temperature
  6. stirringfurther stirred for 2 hours and 30 minutes
  7. extractionextracted with chloroform
  8. dry with materialThe organic layer was dried over magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe resulting residue was purified by silica gel column chromatography (chloroform→chloroform:methanol=80:1→50:1)

Sources & evidence

ORD record
ord-77d8ad8882fc4f6b9b7e4b2f658d85be
Source dataset
uspto-grants-2006_06
Patent number
US07056917B2

Reaction notes

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