2-amino-n-(4-bromophenyl)benzamide → 3-(4-bromophenyl)-2-(4-(2-hydroxyethoxy)-3-methylphenyl)quinazolin-4(3H)-one

HRID 1846311Notes

Reaction equation

HRID 1846311 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[O:10][CH2:11][CH2:12][OH:13])[CH:5]=O.[NH2:14][C:15]1[CH:30]=[CH:29][CH:28]=[CH:27][C:16]=1[C:17]([NH:19][C:20]1[CH:25]=[CH:24][C:23]([Br:26])=[CH:22][CH:21]=1)=[O:18]>C(O)C>[Br:26][C:23]1[CH:24]=[CH:25][C:20]([N:19]2[C:17](=[O:18])[C:16]3[C:15](=[CH:30][CH:29]=[CH:28][CH:27]=3)[N:14]=[C:5]2[C:4]2[CH:7]=[CH:8][C:9]([O:10][CH2:11][CH2:12][OH:13])=[C:2]([CH3:1])[CH:3]=2)=[CH:21][CH:22]=1

Participants

4

Reactant 2

HCID 4788192-amino-n-(4-bromophenyl)benzamideHCID 791110334-(2-Hydroxyethoxy)-3-methylbenzaldehyde

Product 1

HCID 468410103-(4-bromophenyl)-2-(4-(2-hydroxyethoxy)-3-methylphenyl)quinazolin-4(3H)-one

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 3-methyl-4-hydroxyethoxy-benzaldehyde (0.38 g, 2.10 mmol) and 2-amino-N-(4-bromophenyl)benzamide (0.60 g, 2.10 mmol) in anhydrous ethanol (15 mL) was added anhydrous CuCl2 (0.85 g, 6.30 mmol). The reaction mixture was heated at reflux for 18 hours and then cooled to room temperature. Organic solvents were removed under reduced pressure, and the resulting residue was diluted with dichloromethane, washed with water, then brine, and dried over anhydrous magnesium sulfate. The solvent was removed under vacuum and the residual solid was purified by column chromatography (silica gel 230-400 mesh; 25-50% ethyl acetate in hexanes as eluent) to afford the title compound as a white solid. Yield: 0.21 g (22%). MP 92.0-93.0° C. 1H-NMR (400 MHz, CDCl3): δ 8.32 (d, J=8.4 Hz, 1H), 7.81 (dd, J=4.8 and 1.2 Hz, 2H), 7.45-7.54 (m, 3H), 7.23 (m, 1H), 7.00 (m, 3H), 6.63 (d, J=8.4 Hz and 1H), 4.05 (t, J=4.4 Hz, 2H), 3.97 (t, J=4.4 Hz, 2H), 2.15 (s, 3H). MS (ES+) m/z: 453.39, 451.37.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 18 hours
  3. customOrganic solvents were removed under reduced pressure
  4. additionthe resulting residue was diluted with dichloromethane
  5. washwashed with water
  6. dry with materialbrine, and dried over anhydrous magnesium sulfate
  7. customThe solvent was removed under vacuum
  8. customthe residual solid was purified by column chromatography (silica gel 230-400 mesh; 25-50% ethyl acetate in hexanes as eluent)

Sources & evidence

ORD record
ord-eb74b89b6ff64b94a912a6508b691d86
Source dataset
uspto-grants-2015_02
Patent number
US08952021B2

Reaction notes

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