Hydrochloric Acid → 4,9-Dihydro-4-methyl-9-oxo-pyrazolo[5,1-b]quinazoline-2-carboxylic acid, ethyl ester

HRID 443847Notes

Reaction equation

HRID 443847 reaction equation
[H-].[Na+].O=[C:4]1[NH:8][N:7]=[C:6]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:5]1.[H][H].[CH3:16][N:17]1C(=O)O[C:20](=[O:21])[C:19]2=[CH:25][CH:26]=[CH:27][CH:28]=[C:18]12.Cl>CN(C)C=O>[CH3:16][N:17]1[C:18]2[CH:28]=[CH:27][CH:26]=[CH:25][C:19]=2[C:20](=[O:21])[N:8]2[N:7]=[C:6]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH:5]=[C:4]12

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 25160N-Methylisatoic anhydrideHCID 225371Ethyl 5-Oxo-4,5-dihydro-1H-pyrazole-3-carboxylateHCID 178418361HCID 178418361, compound

Product 1

HCID 125525054,9-Dihydro-4-methyl-9-oxo-pyrazolo[5,1-b]quinazoline-2-carboxylic acid, ethyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
90 °C

Procedure

A stirred suspension of 5.3 g of a 50% mineral oil dispersion of sodium hydride in 30 ml of dimethylformamide is treated dropwise at -10° C., under a nitrogen atmosphere, with a solution of 15.6 g of 5-oxo-2-pyrazoline-3-carboxylic acid, ethyl ester, in 65 ml of dimethylformamide. After the evolution of hydrogen ceases, the mixture is stirred for 2 hours while allowing the temperature to rise to +10° C. The mixture is recooled to -10° C. and treated dropwise, with stirring, with a solution of 21.6 g of 90% N-methylisatoic anhydride in 150 ml of dimethylformamide, then stirred for 18 hours while allowing the temperature to rise to 20°-25° C. The mixture is heated at 90° C. for 1 hour, cooled and poured into 3 liters of ice water containing 10 ml of concentrated hydrochloric acid (final pH about 5). The resulting precipitate is collected by filtration and the filtrate is extracted several times with 600 ml portions of dichloromethane. The precipitate is dissolved in 1 liter of dichloromethane and the solution is combined with the above dichloromethane extracts. The combined dichloromethane solution is washed with water, dried and evaporated. The residual oil is triturated with methanol and the resulting solid is collected, dissolved in tetrahydrofuran and the solution is decolorized by passage through an activated magnesium silicate column (Florisil R). The filtrate is concentrated to a small volume, diluted with ethanol and chilled. The resulting crystalline precipitate of 4,9-dihydro-4-methyl-9-oxo-pyrazolo[5,1-b]quinazoline-2-carboxylic acid, ethyl ester is collected by filtration; mp 239°-241° C., after recrystallization from dichloromethane/ethanol.

Workup

  1. customto rise to +10° C
  2. customis recooled to -10° C.
  3. additiontreated dropwise
  4. customto rise to 20°-25° C
  5. temperaturecooled
  6. filtrationThe resulting precipitate is collected by filtration
  7. extractionthe filtrate is extracted several times with 600 ml portions of dichloromethane
  8. dissolutionThe precipitate is dissolved in 1 liter of dichloromethane
  9. washThe combined dichloromethane solution is washed with water
  10. customdried
  11. customevaporated
  12. customThe residual oil is triturated with methanol
  13. customthe resulting solid is collected
  14. dissolutiondissolved in tetrahydrofuran
  15. concentrationThe filtrate is concentrated to a small volume
  16. additiondiluted with ethanol
  17. temperaturechilled
  18. filtrationThe resulting crystalline precipitate of 4,9-dihydro-4-methyl-9-oxo-pyrazolo[5,1-b]quinazoline-2-carboxylic acid, ethyl ester is collected by filtration
  19. custommp 239°-241° C., after recrystallization from dichloromethane/ethanol

Sources & evidence

ORD record
ord-18888e1813894e75a4b08a51bafe65cd
Source dataset
uspto-grants-1981_04
Patent number
US04261997

Reaction notes

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