Hydrochloric Acid → 4-(1,3-dioxolan-2-ylmethyl)-6-(1H-1,2,4-triazol-1-yl)pyrido(2,3-b)pyrazin-3(4H)-one

HRID 385521Notes

Reaction equation

HRID 385521 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:10]=[CH:9][C:8](=[O:11])[N:7]([CH2:12][CH:13]3[O:17][CH2:16][CH2:15][O:14]3)[C:6]=2[N:18]=1.[NH:19]1[CH:23]=[N:22][CH:21]=[N:20]1.[H-].[Na+].Cl>CN(C)C=O.O.C(OCC)(=O)C>[O:14]1[CH2:15][CH2:16][O:17][CH:13]1[CH2:12][N:7]1[C:8](=[O:11])[CH:9]=[N:10][C:5]2[CH:4]=[CH:3][C:2]([N:19]3[CH:23]=[N:22][CH:21]=[N:20]3)=[N:18][C:6]1=2

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 92571H-1,2,4-Triazole2×HCID 24758Sodium hydride2×HCID 578153306-Chloro-4-(1,3-dioxolan-2-ylmethyl)pyrido[2,3-b]pyrazin-3(4h)-one

Product 1

HCID 578152554-(1,3-dioxolan-2-ylmethyl)-6-(1H-1,2,4-triazol-1-yl)pyrido(2,3-b)pyrazin-3(4H)-oneYield 22.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of 0.30 g of 6-chloro-4-(1,3-dioxolan-2-ylmethyl)pyrido(2,3-b)pyrazin-3(4H)-one and 78 mg of 1,2,4-triazole in 9 mL of N,N-dimethylformamide, 48 mg of 60% sodium hydride was added, and the mixture was stirred at 40 to 50° C. for 1 hour 30 minutes. Thereto was further added 78 mg of 1,2,4-triazole and 48 mg of 60% sodium hydride, and the mixture was stirred at 40 to 50° C. for 1 hour 30 minutes, and stirred at 60 to 70° C. for 20 minutes. The reaction mixture was charged with a mixed solution of ethyl acetate and water and neutralized with 2.0 mol/L hydrochloric acid, and the insoluble substance was filtered off. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, the resultant solution was washed sequentially with water and a saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The resultant residue was purified by flash silica gel column chromatography using gradient elution with hexane:ethyl acetate=80:20 to 30:70 and washed with diisopropyl ether to obtain 77 mg of 4-(1,3-dioxolan-2-ylmethyl)-6-(1H-1,2,4-triazole-1-yl)pyrido(2,3-b)pyrazin-3(4H)-one as a light red solid.

Workup

  1. stirringthe mixture was stirred at 40 to 50° C. for 1 hour 30 minutes
  2. stirringstirred at 60 to 70° C. for 20 minutes
  3. filtrationthe insoluble substance was filtered off
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with ethyl acetate
  6. washthe resultant solution was washed sequentially with water
  7. dry with materiala saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate
  8. distillationthe solvent was distilled off under reduced pressure
  9. customThe resultant residue was purified by flash silica gel column chromatography
  10. washelution with hexane
  11. washethyl acetate=80:20 to 30:70 and washed with diisopropyl ether

Sources & evidence

ORD record
ord-bc03d07571074717bf2390b7299283bf
Source dataset
uspto-grants-2013_02
Patent number
US08367831B2

Reaction notes

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