Water → 4-(4-Bromophenyl)-2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4,5,6,7,8-octahydroquinazoline-7-carboxylic acid

HRID 517192Notes

Reaction equation

HRID 517192 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.[O:13]=[C:14]1[CH2:19][CH:18]([C:20]([OH:22])=[O:21])[CH2:17][C:16]([NH:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=2)=[CH:15]1.O.[OH-].[Na+]>ClCCl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:15]3[C:14](=[O:13])[CH2:19][CH:18]([C:20]([OH:22])=[O:21])[CH2:17][C:16]=3[N:23]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:31])([F:32])[F:33])[CH:25]=3)[C:10](=[O:11])[NH:9]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 116874181-Bromo-4-(chloro(isocyanato)methyl)benzeneHCID 867323105-Oxo-3-(3-(trifluoromethyl)phenylamino)cyclohex-3-enecarboxylic acid2×

Product 1

HCID 867323114-(4-Bromophenyl)-2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4,5,6,7,8-octahydroquinazoline-7-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 1-bromo-4-(chloro(isocyanato)methyl)benzene (1.07 g, 4.34 mmol) in dichloromethane (5 mL) is added to a solution of 5-oxo-3-(3-(trifluoromethyl)phenyl-amino)cyclohex-3-enecarboxylic acid (intermediate 22, 1.30 g, 4.34 mmol) in dichloromethane (15 mL) and the mixture is heated at reflux for 3 h. Water and aqueous sodium hydroxide solution are added and the mixture is washed with diethyl ether. The organic layer is discarded and the aqueous layer is acidified with aqueous hydrogen chloride and extracted twice with diethyl ether. The organic layers are combined, dried over Na2SO4 and concentrated under reduced pressure. Yield: 770 mg; ESI mass spectrum: [(79Br)-M+H]+=509, [(81Br)-M+H]+=511; Retention time HPLC: 1.25 min, 1.35 min (1:1 mixture of diastereomers) (V001—006).

Workup

  1. temperaturethe mixture is heated
  2. temperatureat reflux for 3 h
  3. washthe mixture is washed with diethyl ether
  4. extractionextracted twice with diethyl ether
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. additionRetention time HPLC: 1.25 min, 1.35 min (1:1 mixture of diastereomers) (V001—006)

Sources & evidence

ORD record
ord-de780da103414dbcb0a14908f9f79e0c
Source dataset
uspto-grants-2015_08
Patent number
US09115093B2

Reaction notes

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