Butyl isocyanate → 3-n-Butyl-5,6-dimethoxyquinazolin-2,4-(1H, 3H)-dione Hemihydrate

HRID 980892Notes

Reaction equation

HRID 980892 reaction equation
[CH2:1]([N:5]=[C:6]=[O:7])[CH2:2][CH2:3][CH3:4].C([O:10][C:11](=[O:23])[C:12]1[C:17]([O:18][CH3:19])=[C:16]([O:20][CH3:21])[CH:15]=[CH:14][C:13]=1[NH2:22])C>N1C=CC=CC=1.[OH-].[Na+]>[OH2:7].[CH2:1]([N:5]1[C:11](=[O:10])[C:12]2[C:13](=[CH:14][CH:15]=[C:16]([O:20][CH3:21])[C:17]=2[O:18][CH3:19])[NH:22][C:6]1=[O:7])[CH2:2][CH2:3][CH3:4].[CH2:1]([N:5]1[C:11](=[O:23])[C:12]2[C:13](=[CH:14][CH:15]=[C:16]([O:20][CH3:21])[C:17]=2[O:18][CH3:19])[NH:22][C:6]1=[O:7])[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 2

HCID 8110Butyl isocyanateHCID 13749914Ethyl 2,3-dimethoxy-6-aminobenzoate

Product 1

HCID 1317150493-n-Butyl-5,6-dimethoxyquinazolin-2,4-(1H, 3H)-dione Hemihydrate

Reagents, catalysts & solvents 2

HCID 1049PyridineSolvent2×HCID 14798Sodium HydroxideSolvent

Conditions

Temperature
0 °C

Procedure

To n-butyl isocyanate (2.06 g, 2.34 ml, 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, 13.3 mM) in pyridine (16.7 ml). The solution was stirred at 0° C. for thirty minutes, then kept at room temperature for one hour. 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 2 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 afford the title compound as a white solid; 2.38 g (64.3%); mp 159°-161° C.; CDCl3 (TMS) 7.21 (d, 1H, J7,8 =9.0 Hz, 7-H), 6.82 (d, 1H, J8,7 =9.0 Hz, 8-H), 4.10 (t, 2H, J9,10 =7.0 Hz, 9-H), 3.95 (s, 3H, 5 or 6-OCH3), 3.85 (s, 3H, 5 or 6-OCH3), 0.80-2.10 (m, 7H, 10-H, 11-H, 12-H), M+ 278.

Workup

  1. concentrationThe mixture was concentrated to dryness
  2. customto give an off-white solid
  3. temperatureheated
  4. temperatureat reflux for 2 hours
  5. customThe solvent was removed in vacuo
  6. dissolutionthe residue dissolved in H2O (150 ml)
  7. filtrationthe resulting white solid filtered
  8. washwashed with H2O (50 ml)
  9. customdried

Sources & evidence

ORD record
ord-60c51dc23ab6456e9a43eccd9a16f137
Source dataset
uspto-grants-1987_01
Patent number
US04639518

Reaction notes

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