Chlorotrimethylsilane → 1-((4-Bromo-2-methoxyphenyl)(2-hydroxy-6-oxocyclohex-1-enyl)methyl)-3-(3-(trifluoromethyl)phenyl)urea

HRID 517216Notes

Reaction equation

HRID 517216 reaction equation
[C:1]1(=[O:8])[CH2:6][CH2:5][CH2:4][C:3](=[O:7])[CH2:2]1.[Br:9][C:10]1[CH:17]=[CH:16][C:13]([CH:14]=O)=[C:12]([O:18][CH3:19])[CH:11]=1.[F:20][C:21]([F:33])([F:32])[C:22]1[CH:23]=[C:24]([NH:28][C:29]([NH2:31])=[O:30])[CH:25]=[CH:26][CH:27]=1.C[Si](Cl)(C)C>CN(C)C=O.C(#N)C>[Br:9][C:10]1[CH:17]=[CH:16][C:13]([CH:14]([C:2]2[C:3](=[O:7])[CH2:4][CH2:5][CH2:6][C:1]=2[OH:8])[NH:31][C:29]([NH:28][C:24]2[CH:25]=[CH:26][CH:27]=[C:22]([C:21]([F:20])([F:32])[F:33])[CH:23]=2)=[O:30])=[C:12]([O:18][CH3:19])[CH:11]=1

Participants

7

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 104341,3-CyclohexanedioneHCID 25712(3-Trifluoromethylphenyl)ureaHCID 110530414-Bromo-2-methoxybenzaldehyde

Product 1

HCID 867323351-((4-Bromo-2-methoxyphenyl)(2-hydroxy-6-oxocyclohex-1-enyl)methyl)-3-(3-(trifluoromethyl)phenyl)urea

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture of cyclohexane-1,3-dione (700 mg, 6.24 mmol), 4-bromo-2-methoxybenz-aldehyde (1.35 g, 6.28 mmol) and 1-(3-(trifluoromethyl)phenyl)urea (1.27 g, 6.24 mmol) in N,N-dimethylformamide (2.0 mL) and acetonitrile (3.0 mL) is stirred at room temperature for 20 min Trimethylsilyl chloride (1 M in dichloromethane, 9.0 mL, 9.0 mmol) is added, and the mixture is stirred at room temperature for 30 min and poured into ice water. The mixture is stirred for 3 h and concentrated under reduced pressure. The residue is purified by reversed phase HPLC (Waters Xbridge™-C18, gradient of acetonitrile in water, 0.1% NH3). Yield: 900 mg; ESI mass spectrum [(79Br)-M+H]+=513, [(81Br)-M+H]+=515; Retention time HPLC: 0.68 min (Z011_S03).

Workup

  1. additionis added
  2. stirringThe mixture is stirred for 3 h
  3. concentrationconcentrated under reduced pressure
  4. customThe residue is purified by reversed phase HPLC (Waters Xbridge™-C18, gradient of acetonitrile in water, 0.1% NH3)
  5. custom0.68 min (Z011_S03)

Sources & evidence

ORD record
ord-3b3cadaa18144ec88586712e3de4a678
Source dataset
uspto-grants-2015_08
Patent number
US09115093B2

Reaction notes

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