Ethyl isocyanate → Ethyl 8-{[(ethylamino)carbonyl]amino}-1-methyl-1H-pyrazolo[4,3-h]quinazoline-3-carboxylate

HRID 44603Notes

Reaction equation

HRID 44603 reaction equation
[H-].[Na+].[NH2:3][C:4]1[N:13]=[CH:12][C:11]2[CH:10]=[CH:9][C:8]3[C:14]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[N:15][N:16]([CH3:17])[C:7]=3[C:6]=2[N:5]=1.[CH2:23]([N:25]=[C:26]=[O:27])[CH3:24]>CN(C)C=O>[CH2:23]([NH:25][C:26]([NH:3][C:4]1[N:13]=[CH:12][C:11]2[CH:10]=[CH:9][C:8]3[C:14]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[N:15][N:16]([CH3:17])[C:7]=3[C:6]=2[N:5]=1)=[O:27])[CH3:24]

Participants

5

Reactant 3

HCID 8022Ethyl isocyanateHCID 24758Sodium hydrideHCID 57444093Ethyl 8-amino-1-methyl-1H-pyrazolo[4,3-h]quinazoline-3-carboxylate

Product 1

HCID 68938645Ethyl 8-{[(ethylamino)carbonyl]amino}-1-methyl-1H-pyrazolo[4,3-h]quinazoline-3-carboxylateYield 50.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of 18 mg (0.44 mmol) of sodium hydride 60% in mineral oil (0.37 mmol) in dry dimethylformamide, a solution of 100 mg of ethyl 8-amino-1-methyl-1H-pyrazolo[4,3-h]quinazoline-3-carboxylate (0.37 mmol) in 5 mL of the same solvent was added dropwise at 0° C. under stirring. After 5 minutes, 0.070 mL (0.88 mmol) of ethylisocyanate were added to the mixture and the reaction allowed to come to room temperature. After 8 hours the solvent was evaporated under reduced pressure, the residue redissolved with dichloromethane and washed with water. After drying over Na2SO4 the solvent was removed and the product purified by chromatography on a silica gel column (eluant dichloromethane/acetone) leading 64 mg (50% yield) of the title compound.

Workup

  1. customto come to room temperature
  2. customAfter 8 hours the solvent was evaporated under reduced pressure
  3. dissolutionthe residue redissolved with dichloromethane
  4. washwashed with water
  5. dry with materialAfter drying over Na2SO4 the solvent
  6. customwas removed
  7. customthe product purified by chromatography on a silica gel column (eluant dichloromethane/acetone)

Sources & evidence

ORD record
ord-e827da60c73241fba5b1d43526bd142c
Source dataset
uspto-grants-2013_09
Patent number
US08541429B2

Reaction notes

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