4-chloro-N-methylisatoic anhydride → 7-Chloro-3-[3-(1H-imidazol-1-yl)-2-methylpropyl]-1-methyl-2,4(1H,3H)-quinazolinedione

HRID 1788688Notes

Reaction equation

HRID 1788688 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[N:10]([CH3:11])[C:9](=[O:12])[O:8][C:6](=O)[C:5]2=[CH:13][CH:14]=1.[N:15]1([CH2:20][CH:21]([CH3:24])[CH2:22][NH2:23])[CH:19]=[CH:18][N:17]=[CH:16]1>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:5]([C:6](=[O:8])[N:23]([CH2:22][CH:21]([CH3:24])[CH2:20][N:15]3[CH:19]=[CH:18][N:17]=[CH:16]3)[C:9](=[O:12])[N:10]2[CH3:11])=[CH:13][CH:14]=1

Participants

4

Reactant 2

HCID 110529544-chloro-N-methylisatoic anhydrideHCID 139528593-(1H-Imidazol-1-yl)-2-methylpropan-1-amine

Product 1

HCID 139567967-Chloro-3-[3-(1H-imidazol-1-yl)-2-methylpropyl]-1-methyl-2,4(1H,3H)-quinazolinedione

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 2.12 g of 4-chloro-N-methylisatoic anhydride, 1.39 g of 3-(1H-imidazol-1-yl)-2-methylpropanamine and 20 ml of ethanol was stirred at room temperature for 20 hours and concentrated. Ethyl chloroformate (10 ml) was added and the mixture was heated in an oil bath at 90°-105° C. for 2 hours, dissolved in ethanol and concentrated. Ethanol (25 ml) and 2.0 g of potassium hydroxide was added and the mixture was heated at reflux for 3 hours and concentrated. Water was added, and the pH was adjusted to 6-7 with acetic acid. The product was extracted into methylene chloride. Concentration and recrystallization from ethyl acetate resulted in the desired product, mp 206°-209° C.

Workup

  1. concentrationconcentrated
  2. additionEthyl chloroformate (10 ml) was added
  3. temperaturethe mixture was heated in an oil bath at 90°-105° C. for 2 hours
  4. dissolutiondissolved in ethanol
  5. concentrationconcentrated
  6. additionEthanol (25 ml) and 2.0 g of potassium hydroxide was added
  7. temperaturethe mixture was heated
  8. temperatureat reflux for 3 hours
  9. concentrationconcentrated
  10. additionWater was added
  11. extractionThe product was extracted into methylene chloride
  12. concentrationConcentration and recrystallization from ethyl acetate

Sources & evidence

ORD record
ord-4b7d77ef5dee44eeabed2fbed6085bf0
Source dataset
uspto-grants-1987_08
Patent number
US04684654

Reaction notes

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