4-Chlorophenyl Isocyanate → 3-(4-Chlorophenyl)-5,6-dimethoxyquinazolin-2,4(1H, 3H)-dione

HRID 980891Notes

Reaction equation

HRID 980891 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]=[C:9]=[O:10])=[CH:4][CH:3]=1.C([O:13][C:14](=O)[C:15]1[C:20]([O:21][CH3:22])=[C:19]([O:23][CH3:24])[CH:18]=[CH:17][C:16]=1[NH2:25])C>N1C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:14](=[O:13])[C:15]3[C:16](=[CH:17][CH:18]=[C:19]([O:23][CH3:24])[C:20]=3[O:21][CH3:22])[NH:25][C:9]2=[O:10])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 76934-Chlorophenyl IsocyanateHCID 13749914Ethyl 2,3-dimethoxy-6-aminobenzoate

Product 1

HCID 137720283-(4-Chlorophenyl)-5,6-dimethoxyquinazolin-2,4(1H, 3H)-dione

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent3×

Procedure

To p-chlorophenyl isocyanate (2.7 ml, 3.22 g, 20.97 mM) in pyridine (4.7 ml) at 0° C. was added a cold solution of 2-amino-5,6-dimethoxybenzoic acid ethyl ester (3.0 g, 13.32 mM) in pyridine (7.1 ml). The reaction mixture solidified shortly after the addition of the ester. The reaction mixture was allowed to go to room temperature but remained a solid. More pyridine (15 ml) was added and the pink slurry stirred at room temperature for three hours. The solvent was removed in vacuo to give a pink solid. The solid was triturated with 300 ml of 1N NaOH (4:1, MeOH:H2O) was added and the solution was heated at reflux for 2 hours. The solvent was removed in vacuo and the reddish solid partially dissolved in H2O (25 ml). The pH was adjusted to 5 with acetic acid and the resulting solid filtered, washed with H2O (~75 ml) and dried to give crude product as a pink solid. The crude product was triturated with MeOH. The insoluble solid was filtered to afford the title compound as a white solid; 2.66 g; mp 269°-273° C., CF3COOH(TMS), 7.10-7.77 (m, 6H, 7-H, 8-H, 9-H, 10-H, 12-H 13-H), 4.12 (s, 3H, 5 or 6-OCH3), 4.07 (s, 3H, 5 or 6-OCH3); M+ 332.

Workup

  1. customto go to room temperature
  2. customThe solvent was removed in vacuo
  3. customto give a pink solid
  4. customThe solid was triturated with 300 ml of 1N NaOH (4:1, MeOH:H2O)
  5. additionwas added
  6. temperaturethe solution was heated
  7. temperatureat reflux for 2 hours
  8. customThe solvent was removed in vacuo
  9. dissolutionthe reddish solid partially dissolved in H2O (25 ml)
  10. filtrationthe resulting solid filtered
  11. washwashed with H2O (~75 ml)
  12. customdried
  13. customto give crude product as a pink solid
  14. customThe crude product was triturated with MeOH
  15. filtrationThe insoluble solid was filtered

Sources & evidence

ORD record
ord-65b0a1b2afac4d12a69a44ffedf0ecc4
Source dataset
uspto-grants-1987_01
Patent number
US04639518

Reaction notes

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