Water → 3-(2-(4-(5,7-Dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)-1-isopropylimidazolidine-2,4-dione

HRID 591735Notes

Reaction equation

HRID 591735 reaction equation
[CH:1]([N:4]1[CH2:8][C:7](=[O:9])[NH:6][C:5]1=[O:10])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:14][CH2:15][O:16][C:17]1[C:22]([CH3:23])=[CH:21][C:20]([C:24]2[NH:33][C:32](=[O:34])[C:31]3[C:26](=[CH:27][C:28]([O:37][CH3:38])=[CH:29][C:30]=3[O:35][CH3:36])[N:25]=2)=[CH:19][C:18]=1[CH3:39].O>CN(C)C=O>[CH3:36][O:35][C:30]1[CH:29]=[C:28]([O:37][CH3:38])[CH:27]=[C:26]2[C:31]=1[C:32](=[O:34])[NH:33][C:24]([C:20]1[CH:21]=[C:22]([CH3:23])[C:17]([O:16][CH2:15][CH2:14][N:6]3[C:7](=[O:9])[CH2:8][N:4]([CH:1]([CH3:3])[CH3:2])[C:5]3=[O:10])=[C:18]([CH3:39])[CH:19]=1)=[N:25]2

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 102194852,4-Imidazolidinedione, 1-(1-methylethyl)-HCID 1364005142-[4-(2-bromoethoxy)-3,5-dimethylphenyl]-5,7-dimethoxy-3H-quinazolin-4-one

Product 1

HCID 1363480383-(2-(4-(5,7-Dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)-1-isopropylimidazolidine-2,4-dione

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-isopropyl-imidazolidine-2,4-dione (0.10 g, 0.70 mmol) in N,N-dimethylformamide (5 mL) was added sodium hydride (60% in mineral oil, 31 mg, 0.77 mmol) and the reaction mixture was stirred for 10 minutes. Then, 2-[4-(2-bromo-ethoxy)-3,5-dimethyl-phenyl]-5,7-dimethoxy-3H-quinazolin-4-one (0.32 g, 0.73 mmol) was added. The reaction mixture was stirred at 55° C. for 16 hours, then poured into water (100 mL). The solid was filtered and dried. The crude compound was purified by column chromatography (silica gel 230-400 mesh; eluting with 2:1 ethyl acetate and dichloromethane) to give the title compound as a white solid. Yield: 0.09 g (26.0%). MP 219-221° C. 1H NMR (400 MHz, DMSO): δ 9.64 (s, 1H), 7.69 (s, 2H), 6.82 (d, J=2.4 Hz, 1H), 6.45 (d, J=2.4 Hz, 1H), 4.42 (m, 1H), 4.02 (m, 2H), 3.98 (m, 2H), 3.96 (s, 3H), 3.92 (s, 3H), 3.85 (s, 2H), 2.32 (s, 6H) 1.22 (d, J=6.4 Hz, 6H). MS (ES+) m/z: 495.16 (M+1).

Workup

  1. stirringThe reaction mixture was stirred at 55° C. for 16 hours
  2. filtrationThe solid was filtered
  3. customdried
  4. customThe crude compound was purified by column chromatography (silica gel 230-400 mesh; eluting with 2:1 ethyl acetate and dichloromethane)

Sources & evidence

ORD record
ord-efed34372ffe43c4a0c3be0550a6cc55
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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