5-Phenyl-3-{[3-(trifluoromethyl)phenyl]amino}cyclohex-2-en-1-one → 4-(4-Bromophenyl)-7-phenyl-1-(3-(trifluoromethyl)phenyl)-3,4,7,8-tetrahydroquinazoline-2,5(1H,6H)-dione

HRID 517184Notes

Reaction equation

HRID 517184 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8](Cl)[N:9]=[C:10]=[O:11])=[CH:4][CH:3]=1.[C:13]1([CH:19]2[CH2:24][C:23](=[O:25])[CH:22]=[C:21]([NH:26][C:27]3[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:36])([F:35])[F:34])[CH:28]=3)[CH2:20]2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>ClCCl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:22]3[C:23](=[O:25])[CH2:24][CH:19]([C:13]4[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=4)[CH2:20][C:21]=3[N:26]([C:27]3[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:34])([F:35])[F:36])[CH:28]=3)[C:10](=[O:11])[NH:9]2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 51584005-Phenyl-3-{[3-(trifluoromethyl)phenyl]amino}cyclohex-2-en-1-one2×HCID 116874181-Bromo-4-(chloro(isocyanato)methyl)benzene

Product 1

HCID 867323034-(4-Bromophenyl)-7-phenyl-1-(3-(trifluoromethyl)phenyl)-3,4,7,8-tetrahydroquinazoline-2,5(1H,6H)-dione

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 1-bromo-4-(chloro(isocyanato)methyl)benzene (201 mg, 0.815 mmol) in dichloromethane (3 mL) is added to a solution of 5-phenyl-3-(3-(trifluoromethyl)phenyl-amino)cyclohex-2-enone (intermediate 14, 270 mg, 0.815 mmol) in dichloromethane (7 mL), and the mixture is heated at reflux for 4 h and cooled to room temperature. After 2 d the mixture is concentrated under reduced pressure and the residue is purified by flash chromatography on silica (gradient cyclohexane/ethyl acetate 90:10 to 60:40). Yield: 195 mg; ESI mass spectrum: [(79Br)-M+H]+=541, [(81Br)-M+H]+=543; Retention time HPLC: 1.42 min, 1.44 min (1:1 mixture of diastereomers) (Z002—002).

Workup

  1. temperaturethe mixture is heated
  2. temperatureat reflux for 4 h
  3. concentrationAfter 2 d the mixture is concentrated under reduced pressure
  4. customthe residue is purified by flash chromatography on silica (gradient cyclohexane/ethyl acetate 90:10 to 60:40)
  5. additionRetention time HPLC: 1.42 min, 1.44 min (1:1 mixture of diastereomers) (Z002—002)

Sources & evidence

ORD record
ord-70c9e7cae6614b08b23f83e1df5f1357
Source dataset
uspto-grants-2015_08
Patent number
US09115093B2

Reaction notes

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