Ammonia → (E)-3-[6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]acrylamide

HRID 546755Notes

Reaction equation

HRID 546755 reaction equation
ClC(OC(C)C)=O.[CH3:8][O:9][C:10]1[N:15]=[C:14](/[CH:16]=[CH:17]/[C:18](O)=[O:19])[CH:13]=[CH:12][C:11]=1[N:21]1[CH:25]=[C:24]([CH3:26])[N:23]=[CH:22]1.C([N:30](CC)C(C)C)(C)C.ClC(OCC)=O.N>CN(C=O)C.O.C(Cl)(Cl)Cl>[CH3:8][O:9][C:10]1[N:15]=[C:14](/[CH:16]=[CH:17]/[C:18]([NH2:30])=[O:19])[CH:13]=[CH:12][C:11]=1[N:21]1[CH:25]=[C:24]([CH3:26])[N:23]=[CH:22]1

Participants

9

Reactant 5

HCID 222AmmoniaHCID 7917Isopropyl chloroformateHCID 10928Ethyl chloroformateHCID 81531Diisopropylethylamine2×HCID 66633906(E)-3-[6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]acrylic acid2×

Product 1

HCID 66839442(E)-3-[6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]acrylamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent2×

Procedure

Isopropyl chloroformate (3.99 mL) was added dropwise to a solution of (E)-3-[6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]acrylic acid (5.2 g) and N,N-diisopropylethylamine (7.44 mL) in DMF (52 mL) under ice-cooling, and the reaction solution was stirred for 20 minutes. Aqueous ammonic (5.2 mL) was added to the reaction solution, and the reaction solution was stirred at room temperature for 30 minutes. Similarly, ethyl chloroformate (3.76 mL) was added dropwise to a solution of (E)-3-[6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]acrylic acid (4.8 g) and N,N-diisopropylethylamine (6.87 mL) in DMF (48 mL) under ice-cooling, and the reaction solution was stirred for 10 minutes. Then, aqueous ammonia (5.2 mL) was added to the reaction solution, and the reaction solution was stirred at room temperature for 30 minutes. The reaction solutions were mixed and diluted with water and chloroform, and then the organic layer was separated. The aqueous layer was extracted with chloroform five times. The organic layers were combined, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform-2-propanol system) to obtain 3.54 g of the title compound. The property value of the compound is as follows.

Workup

  1. temperaturecooling
  2. additionAqueous ammonic (5.2 mL) was added to the reaction solution
  3. stirringthe reaction solution was stirred at room temperature for 30 minutes
  4. temperaturecooling
  5. stirringthe reaction solution was stirred for 10 minutes
  6. stirringthe reaction solution was stirred at room temperature for 30 minutes
  7. additionThe reaction solutions were mixed
  8. customthe organic layer was separated
  9. extractionThe aqueous layer was extracted with chloroform five times
  10. dry with materialdried over anhydrous magnesium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by silica gel column chromatography (chloroform-2-propanol system)

Sources & evidence

ORD record
ord-f6431c0d6c76467789babd2b3122fc03
Source dataset
uspto-grants-2011_05
Patent number
US07935815B2

Reaction notes

Loading…