Water → 4-(4-Bromophenyl)-1-(3-(difluoromethyl)phenyl)-3,4,6,7-tetrahydro-1H-cyclopenta[d]-pyrimidine-2,5-dione

HRID 927193Notes

Reaction equation

HRID 927193 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.[F:13][CH:14]([F:28])[C:15]1[CH:16]=[C:17]([NH:21][C:22]2[CH2:26][CH2:25][C:24](=[O:27])[CH:23]=2)[CH:18]=[CH:19][CH:20]=1.O>ClCCl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[NH:9][C:10](=[O:11])[N:21]([C:17]3[CH:18]=[CH:19][CH:20]=[C:15]([CH:14]([F:13])[F:28])[CH:16]=3)[C:22]3[CH2:26][CH2:25][C:24](=[O:27])[C:23]2=3)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 962WaterHCID 116874181-Bromo-4-(chloro(isocyanato)methyl)benzeneHCID 903109643-(3-(Difluoromethyl)phenylamino)cyclopent-2-enone2×

Product 1

HCID 903110614-(4-Bromophenyl)-1-(3-(difluoromethyl)phenyl)-3,4,6,7-tetrahydro-1H-cyclopenta[d]-pyrimidine-2,5-dione

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 1-bromo-4-(chloro(isocyanato)methyl)benzene (240 mg, 0.974 mmol) in dichloromethane (2 mL) is added dropwise to a solution of 3-(3-(difluoromethyl)phenyl-amino)cyclopent-2-enone (intermediate 5, 217 mg, 0.974 mmol) in dichloromethane (2 mL) and the reaction mixture is heated at reflux for 2 h. Water is added, and the phases are extracted twice with dichloromethane. The combined organic layers are concentrated and the residue is purified by flash chromatography on silica (gradient cyclohexane/ethyl acetate 4:1 to ethyl acetate). Yield: 159 mg; ESI mass spectrum: [(79Br)-M+H]+=433, [(81Br)-M+H]+=435; Retention time HPLC: 0.56 min (X012_S01).

Workup

  1. temperaturethe reaction mixture is heated
  2. temperatureat reflux for 2 h
  3. extractionthe phases are extracted twice with dichloromethane
  4. concentrationThe combined organic layers are concentrated
  5. customthe residue is purified by flash chromatography on silica (gradient cyclohexane/ethyl acetate 4:1 to ethyl acetate)
  6. custom0.56 min (X012_S01)

Sources & evidence

ORD record
ord-f87c092bff3b4f0e9819029150100ea2
Source dataset
uspto-grants-2016_03
Patent number
US09290459B1

Reaction notes

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