p-Toluenesulfonic acid monohydrate → 3-(4-(5,7-Dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)benzyl)imidazolidine-2,4-dione

HRID 591755Notes

Reaction equation

HRID 591755 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[C:7]([O:13][CH3:14])[C:3]=1[C:4]([NH2:6])=[O:5].[O:15]=[C:16]1[NH:20][CH2:19][C:18](=[O:21])[N:17]1[CH2:22][C:23]1[CH:30]=[CH:29][C:26]([CH:27]=O)=[CH:25][CH:24]=1.S([O-])(O)=O.[Na+].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CN(C)C(=O)C>[CH3:14][O:13][C:7]1[CH:8]=[C:9]([O:11][CH3:12])[CH:10]=[C:2]2[C:3]=1[C:4](=[O:5])[NH:6][C:27]([C:26]1[CH:25]=[CH:24][C:23]([CH2:22][N:17]3[C:18](=[O:21])[CH2:19][NH:20][C:16]3=[O:15])=[CH:30][CH:29]=1)=[N:1]2

Participants

6

Reactant 4

HCID 521998p-Toluenesulfonic acid monohydrateHCID 187585643-(4-Formylbenzyl)hydantoinHCID 203490162-Amino-4,6-dimethoxybenzamideHCID 23665763Sodium Bisulfite

Product 1

HCID 1363480223-(4-(5,7-Dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)benzyl)imidazolidine-2,4-dione

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
115 °C

Procedure

To a solution of 2-amino-4,6-dimethoxy-benzamide (0.19 g, 0.98 mmol) in N,N-dimethylacetamide (4 mL) were added 4-(2,5-dioxo-imidazolidin-1-ylmethyl)-benzaldehyde (0.19 g, 0.89 mmol), sodium hydrogen sulfite (58.5 wt %, 0.24 g, 1.30 mmol) and p-toluenesulfonic acid monohydrate (34 mg, 0.18 mmol) and the reaction mixture was stirred at 115° C. for 17 hours under nitrogen, then cooled to room temperature. The precipitate was filtered, washed with methanol, water, then methanol, and dried in air. The solid was suspended in hot DMSO (approximately 3 mL); saturated aqueous NaHCO3 (approximately 3 mL) and water were added. The solid was filtered, washed with water, then methanol, and air dried to give the title compound as a light yellow solid. Yield: 0.16 g (46%). MP 317-318° C. 1H NMR (400 MHz, DMSO-d6): δ 12.05 (s, 1H), 8.17 (s, 1H), 8.12 (d, J=8.4 Hz, 2H), 7.40 (d, J=8.4 Hz, 2H), 6.74 (d, J=2.0 Hz, 1H), 6.54 (d, J=2.0 Hz, 1H), 4.61 (s, 2H), 4.02 (s, 2H), 3.89 (s, 3H), 3.85 (s, 3H). MS (ES+) m/z: 395.09 (M+1).

Workup

  1. temperaturecooled to room temperature
  2. filtrationThe precipitate was filtered
  3. washwashed with methanol, water
  4. dry with materialmethanol, and dried in air
  5. additionsaturated aqueous NaHCO3 (approximately 3 mL) and water were added
  6. filtrationThe solid was filtered
  7. washwashed with water
  8. dry with materialmethanol, and air dried

Sources & evidence

ORD record
ord-57c286a506b047f180b30d2d68b757df
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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