Ethyl isocyanate → 3-Ethyl-5,6-dimethoxyquinazolin-2,4(1H, 3H)-dione

HRID 980890Notes

Reaction equation

HRID 980890 reaction equation
[CH2:1]([N:3]=[C:4]=[O:5])[CH3:2].C([O:8][C:9](=O)[C:10]1[C:15]([O:16][CH3:17])=[C:14]([O:18][CH3:19])[CH:13]=[CH:12][C:11]=1[NH2:20])C>N1C=CC=CC=1.[OH-].[Na+]>[CH2:1]([N:3]1[C:9](=[O:8])[C:10]2[C:11](=[CH:12][CH:13]=[C:14]([O:18][CH3:19])[C:15]=2[O:16][CH3:17])[NH:20][C:4]1=[O:5])[CH3:2]

Participants

5

Reactant 2

HCID 8022Ethyl isocyanateHCID 13749914Ethyl 2,3-dimethoxy-6-aminobenzoate

Product 1

HCID 542515083-Ethyl-5,6-dimethoxyquinazolin-2,4(1H, 3H)-dioneYield 80.5%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolvent2×HCID 14798Sodium HydroxideSolvent

Conditions

Temperature
0 °C

Procedure

To ethyl isocyanate (1.65 ml, 1.48 g, 20.8 mM) in pyridine (9.2 ml) at 0° C. was added a cold solution of 2-amino-5,6-dimethoxybenzoic acid ethyl ester (3.0 g, 20.8 mM) in pyridine (16.7 ml). The solution was stirred at 0° C. for thirty minutes, then kept at room temperature for one hour. During this time, a precipitate formed. The mixture was concentrated to dryness to give an off-white solid. This was dissolved in 69.9 ml of 1N NaOH (4:1 MeOH-H2O) and heated at reflux for two hours. The solvent was removed in vacuo and the residue dissolved in H2O (150 ml). The mixture was taken to pH 6 with acetic acid and the resulting white solid filtered, washed with H2O (50 ml), and dried to give crude product as a white solid; 3.12 g; mp 208°-211° C. Recrystallization from isopropanol (100 ml) and drying afforded the title compound as a white solid; 2.09 g; mp 212°-214° C., total yield 80.5%, CF3COOH(TMS), 7.60 (d, 1H, J7,8 =9.0 Hz, 7-H), 7.13 (d, 1H, J8,7 =9.0 Hz, 8-H), 4.20 (9, 2H, J=6.0 Hz, 9-H), 4.19 (s, 3H, 5 or 6-OCH3), 4.05 (s, 3H, 5 or 6-OCH3), 1.40 (t, 3H, J=6.0 Hz, 10-H). M+ 250.

Workup

  1. customDuring this time, a precipitate formed
  2. concentrationThe mixture was concentrated to dryness
  3. customto give an off-white solid
  4. temperatureheated
  5. temperatureat reflux for two hours
  6. customThe solvent was removed in vacuo
  7. dissolutionthe residue dissolved in H2O (150 ml)
  8. filtrationthe resulting white solid filtered
  9. washwashed with H2O (50 ml)
  10. customdried
  11. customto give crude product as a white solid
  12. customRecrystallization from isopropanol (100 ml)
  13. customdrying

Sources & evidence

ORD record
ord-2cc5331e6cd74d5b840e9813827467e7
Source dataset
uspto-grants-1987_01
Patent number
US04639518

Reaction notes

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