Water → HCID 118691682, compound

HRID 927004Notes

Reaction equation

HRID 927004 reaction equation
CI.[CH2:3]([O:5][C:6]([C:8]1[CH:9]([C:26]2[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[CH:28][C:27]=2[Br:34])[NH:10][C:11](=[O:25])[N:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=2)[C:13]=1[CH3:14])=[O:7])[CH3:4].[C:35](=O)([O-])[O-].[Cs+].[Cs+].O>CN(C)C=O.C(OCC)(=O)C>[CH2:3]([O:5][C:6]([C:8]1[CH:9]([C:26]2[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[CH:28][C:27]=2[Br:34])[N:10]([CH3:35])[C:11](=[O:25])[N:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:22])[F:23])[CH:16]=2)[C:13]=1[CH3:14])=[O:7])[CH3:4]

Participants

7

Reactant 4

HCID 962WaterHCID 6328Methyl iodide2×HCID 10796Cesium carbonate2×HCID 1186916704-(2-Bromo-4-cyano-phenyl)-6-methyl-2-oxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester2×

Product 1

HCID 118691682HCID 118691682, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Methyliodide (c=2 mol/L, 1.1 mL, 17.7 mmol) is added to a solution 4-(2-Bromo-4-cyano-phenyl)-6-methyl-2-oxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester (intermediate 7. 47 g, 14.7 mmol) and cesium carbonate (7.9 g, 24.3 mmol) in N,N-dimethylformamide (80 mL). The mixture is stirred at room temperature overnight. Additional methyliodide (c=2 mol/L, 1.1 mL, 17.7 mmol) and cesium carbonate (5.0 g, 15.4 mmol) are added and the reaction is continued for 5 h. Water and ethyl acetate are added and the phases are separated. The aqueous phase is extracted twice with ethyl acetate and the combined organic phases are washed with saturated sodium chloride solution, dried over MgSO4 and concentrated. The residue is purified by reversed phase HPLC. Yield: 7.61 g. ESI mass spectrum: [M+H]+=522; Retention time HPLC: 1.20 min (HPLC method Z018_S04).

Workup

  1. waitthe reaction is continued for 5 h
  2. customthe phases are separated
  3. extractionThe aqueous phase is extracted twice with ethyl acetate
  4. washthe combined organic phases are washed with saturated sodium chloride solution
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe residue is purified by reversed phase HPLC
  8. custom1.20 min (HPLC method Z018_S04)

Sources & evidence

ORD record
ord-74431344ed8f46cd92bf3e8be8bfbddb
Source dataset
uspto-grants-2016_03
Patent number
US09290457B2

Reaction notes

Loading…