4-(2-Hydroxyethoxy)-3,5-dimethylbenzaldehyde → 3-(4-sec-butylphenyl)-2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-8-methoxyquinazolin-4(3H)-one

HRID 1846296Notes

Reaction equation

HRID 1846296 reaction equation
[NH2:1][C:2]1[C:20]([O:21][CH3:22])=[CH:19][CH:18]=[CH:17][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([CH:13]([CH2:15][CH3:16])[CH3:14])=[CH:9][CH:8]=1)=[O:5].[OH:23][CH2:24][CH2:25][O:26][C:27]1[C:34]([CH3:35])=[CH:33][C:30]([CH:31]=O)=[CH:29][C:28]=1[CH3:36]>[Cu](Cl)Cl.C(O)C>[CH:13]([C:10]1[CH:9]=[CH:8][C:7]([N:6]2[C:4](=[O:5])[C:3]3[C:2](=[C:20]([O:21][CH3:22])[CH:19]=[CH:18][CH:17]=3)[N:1]=[C:31]2[C:30]2[CH:33]=[C:34]([CH3:35])[C:27]([O:26][CH2:25][CH2:24][OH:23])=[C:28]([CH3:36])[CH:29]=2)=[CH:12][CH:11]=1)([CH2:15][CH3:16])[CH3:14]

Participants

5

Reactant 2

HCID 289325784-(2-Hydroxyethoxy)-3,5-dimethylbenzaldehydeHCID 866598052-amino-N-(4-sec-butyl-phenyl)-3-methoxy-benzamide

Product 1

HCID 468408743-(4-sec-butylphenyl)-2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-8-methoxyquinazolin-4(3H)-one

Reagents, catalysts & solvents 2

HCID 24014Cupric ChlorideCatalystHCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

To a 100-mL round bottom flask were added 2-amino-N-(4-sec-butyl-phenyl)-3-methoxy-benzamide (0.533 g, 1.79 mmol), 4-(2-hydroxy-ethoxy)-3,5-dimethyl-benzaldehyde (0.382 g, 1.96 mmol), anhydrous copper (II) chloride (0.722 g, 5.37 mmol), and anhydrous ethanol (40 mL). The mixture was refluxed at 100° C. under N2 for 5 hours. The mixture was concentrated to dryness. Water (approximately 20 mL) was added and extracted with EtOAc (3×50 mL). The EtOAc solutions were combined and dried over Na2SO4. The crude product was purified by column chromatography on silica gel using hexane/EtOAc (1:1 to 1:2) as eluent. The product fractions were concentrated to dryness then re-crystallized in ether to afford the title compound as white solid. Yield: 0.460 g (54%). MP 158-159° C. 1H-NMR (400 MHz, CDCl3): δ 7.93 (d, 1H), 7.46 (t, 1H), 7.24 (d, 1H), 7.12 (d, 2H), 7.05 (d, 2H), 7.00 (s, 2H), 4.03 (s, 3H), 3.89 (m, 2H), 3.75 (m, 2H), 2.56 (m, 1H), 2.11 (s, 6H), 1.52 (m, 2H), 1.19 (d, 3H), 0.72 (t, 3H). MS (ES+) m/z: 473.27 (M+1).

Workup

  1. concentrationThe mixture was concentrated to dryness
  2. additionWater (approximately 20 mL) was added
  3. extractionextracted with EtOAc (3×50 mL)
  4. dry with materialdried over Na2SO4
  5. customThe crude product was purified by column chromatography on silica gel
  6. concentrationThe product fractions were concentrated to dryness
  7. customthen re-crystallized in ether

Sources & evidence

ORD record
ord-058ebdeae73445c480e6265eb0eaeb14
Source dataset
uspto-grants-2015_02
Patent number
US08952021B2

Reaction notes

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