2-amino-n-(4-bromophenyl)benzamide → 3-(4-bromophenyl)-2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)quinazolin-4(3H)-one

HRID 1846264Notes

Reaction equation

HRID 1846264 reaction equation
[NH2:1][C:2]1[CH:17]=[CH:16][CH:15]=[CH:14][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([Br:13])=[CH:9][CH:8]=1)=[O:5].[OH:18][CH2:19][CH2:20][O:21][C:22]1[C:29]([CH3:30])=[CH:28][C:25]([CH:26]=O)=[CH:24][C:23]=1[CH3:31]>C(O)C.[Cu](Cl)Cl>[Br:13][C:10]1[CH:11]=[CH:12][C:7]([N:6]2[C:4](=[O:5])[C:3]3[C:2](=[CH:17][CH:16]=[CH:15][CH:14]=3)[N:1]=[C:26]2[C:25]2[CH:28]=[C:29]([CH3:30])[C:22]([O:21][CH2:20][CH2:19][OH:18])=[C:23]([CH3:31])[CH:24]=2)=[CH:8][CH:9]=1

Participants

5

Reactant 2

HCID 4788192-amino-n-(4-bromophenyl)benzamideHCID 289325784-(2-Hydroxyethoxy)-3,5-dimethylbenzaldehyde

Product 1

HCID 468407393-(4-bromophenyl)-2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)quinazolin-4(3H)-one

Reagents, catalysts & solvents 2

HCID 24014Cupric ChlorideCatalystHCID 702EthanolSolvent

Procedure

To a solution of 2-amino-N-(4-bromo-phenyl)-benzamide (3.75 g, 12.9 mmol) and 4-(2-hydroxy-ethoxy)-3,5-dimethyl-benzaldehyde (D) (2.50 g, 12.9 mmol) in anhydrous ethanol (75 mL) was added anhydrous copper (II) chloride (5.19 g, 38.6 mmol). The reaction mixture was stirred under reflux for 16 hours under nitrogen, then cooled to room temperature. The ethanol was evaporated under reduced pressure. The residue was taken in dichloromethane (300 mL) and the organic phase was washed with water (200 mL). The aqueous phase was then extracted with CH2Cl2 (2×200 mL). The combined organic phase was washed with brine (200 mL) and dried over anhydrous Na2SO4. The solvent was evaporated. The crude compound was purified by column chromatography (silica gel 230-400 mesh; 30-50% ethyl acetate in hexanes as eluent) to give the title compound (K) as white solid. Yield: 3.84 g (64%). MP 164-165° C. 1H-NMR (400 MHz, DMSO-d6): δ 8.33 (d, J=7.80 Hz, 1H), 7.82-7.80 (m, 2H), 7.55-7.45 (m, 3H), 7.04 (d, J=8.58 Hz, 2H), 6.98 (s, 2H), 3.94-3.90 (m, 2H), 3.82 (t, J=4.68 Hz, 2H), 2.17 (s, 6H), 2.13 (t, J=3.51 Hz, 1H). MS (ES+) m/z: 465.42 (97%) (M+1), 467.43 (100%) (M+3).

Workup

  1. temperatureunder reflux for 16 hours under nitrogen
  2. customThe ethanol was evaporated under reduced pressure
  3. washthe organic phase was washed with water (200 mL)
  4. extractionThe aqueous phase was then extracted with CH2Cl2 (2×200 mL)
  5. washThe combined organic phase was washed with brine (200 mL)
  6. dry with materialdried over anhydrous Na2SO4
  7. customThe solvent was evaporated
  8. customThe crude compound was purified by column chromatography (silica gel 230-400 mesh; 30-50% ethyl acetate in hexanes as eluent)

Sources & evidence

ORD record
ord-1ab456d8390f440f8056f3dd0a5cc412
Source dataset
uspto-grants-2015_02
Patent number
US08952021B2

Reaction notes

Loading…