Glyoxal → tert-Butyl 7H-pyrrolo[3',4':3,4]pyrazolo[1,5-b][1,2,4]triazine-8(9H)-carboxylate

HRID 2264310Notes

Reaction equation

HRID 2264310 reaction equation
[NH2:1][C:2]1[NH:6][N:5]=[C:4]2[CH2:7][N:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:9][C:3]=12.[OH-].[K+].NOS(O)(=O)=O.[CH:25]([CH:27]=O)=O.[Cl-].[NH4+:30].[Cl-].[Na+].O>CN(C)C=O.O.C(O)C>[N:1]1[C:2]2[N:6]([N:5]=[C:4]3[CH2:7][N:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:9][C:3]=23)[N:30]=[CH:25][CH:27]=1

Participants

9

Reactant 5

HCID 7860GlyoxalHCID 14797Potassium HydroxideHCID 76284hydroxylamine-O-sulfonic acidHCID 131728592Ammonium chloride brineHCID 178451527HCID 178451527, compound

Product 1

HCID 86639710tert-Butyl 7H-pyrrolo[3',4':3,4]pyrazolo[1,5-b][1,2,4]triazine-8(9H)-carboxylate

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 0.2 g (0.89 mmol) of tert-butyl 3-amino-2,6-dihydropyrrolo[3,4-c]pyrazole-5(4H)-carboxylate in N,N-dimethylformamide (4 mL) at −10° C. was added 0.37 g (5.6 mmol) of powdered potassium hydroxide. The reaction mixture was stirred between 0° C. and −10° C. for 20 min. To this mixture was added 0.2 g (1.78 mmol) of hydroxylamine-O-sulfonic acid in eight portions over 20 min while maintaining the temperature between 0° C. and −10° C. Stirring was continued for 45 min while keeping the temperature below 5° C. Ethanol (4 mL) was added slowly to maintain the temperature below 5° C. and 0.2 mL (1.78 mmol) of 40% glyoxal in water was added. The reaction mixture was stirred below 5° C. for 15 min, warmed to ambient temperature over 15 min and stirred at ambient temperature for 45 min. The reaction mixture was cooled to below 5° C. and a 1:1 mixture of half saturated aqueous ammonium chloride/brine (15 mL) was added. The reaction mixture was extracted with ethyl acetate (4×15 mL), and the combined organic phases washed with saturated aqueous brine (15 mL), dried over anhydrous magnesium sulfate, filtered and the solvent evaporated in vacuo. The residue was purified by flash chromatography on a Biotage Horizon® system (silica gel, 0 to 40% hexanes/ethyl acetate gradient) to yield the title compound as a yellow solid. LC/MS 262.2 (M+1).

Workup

  1. temperaturewhile maintaining the temperature between 0° C. and −10° C
  2. stirringStirring
  3. waitwas continued for 45 min
  4. customthe temperature below 5° C
  5. additionwas added
  6. stirringThe reaction mixture was stirred below 5° C. for 15 min
  7. stirringstirred at ambient temperature for 45 min
  8. temperatureThe reaction mixture was cooled to below 5° C.
  9. additionwas added
  10. extractionThe reaction mixture was extracted with ethyl acetate (4×15 mL)
  11. washthe combined organic phases washed with saturated aqueous brine (15 mL)
  12. dry with materialdried over anhydrous magnesium sulfate
  13. filtrationfiltered
  14. customthe solvent evaporated in vacuo
  15. customThe residue was purified by flash chromatography on a Biotage Horizon® system (silica gel, 0 to 40% hexanes/ethyl acetate gradient)

Sources & evidence

ORD record
ord-1ba9dd0d47674106b9b9da396928b0d6
Source dataset
uspto-grants-2010_12
Patent number
US07855206B2

Reaction notes

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