Sodium Iodide → 3-(4-Chlorobenzyl)-6-[4-(4-fluorophenyl)piperazin-1-yl]-1,3,5-triazine-2,4(1H,3H)-dione

HRID 1477577Notes

Reaction equation

HRID 1477577 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]3[NH:19][C:18](=[O:20])[NH:17][C:16](=[O:21])[N:15]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[H-].[Li+].[Cl:24][C:25]1[CH:32]=[CH:31][C:28]([CH2:29]Cl)=[CH:27][CH:26]=1.[I-].[Na+]>O.CN(C)C=O>[Cl:24][C:25]1[CH:32]=[CH:31][C:28]([CH2:29][N:17]2[C:18](=[O:20])[N:19]=[C:14]([N:11]3[CH2:12][CH2:13][N:8]([C:5]4[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=4)[CH2:9][CH2:10]3)[NH:15][C:16]2=[O:21])=[CH:27][CH:26]=1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 77231-Chloro-4-(chloromethyl)benzeneHCID 62714Lithium hydrideHCID 1178393346-[4-(4-Fluorphenyl)piperazin-1-yl]-1,3,5-triazine-2,4(1H,3H)-dione

Product 1

HCID 1178393463-(4-Chlorobenzyl)-6-[4-(4-fluorophenyl)piperazin-1-yl]-1,3,5-triazine-2,4(1H,3H)-dioneYield 16.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To an N,N-dimethylformamide solution of 6-[4-(4-fluorophenyl)piperazin-1-yl]-1,3,5-triazine-2,4(1H,3H)-dione (1.20 g, 4.12 mmol) synthesized in Reference Synthesis Example 18, lithium hydride (75 mg, 4.94 mmol), 4-chlorobenzyl chloride (0.70 g, 4.12 mmol), and sodium iodide (catalytic amount) were added at room temperature and the resultant solution was stirred at 50° C. for 8 hours. After completion of the reaction, the reaction solution was poured into water and the resultant mixture was washed with ethyl acetate. Diluted hydrochloric acid was added to the water phase to adjust pH to 3 and the obtained solid was collected by filtration. Extraction with a mixed solution of ethyl acetate and tetrahydrofuran from the filtrate was performed and the organic layer was concentrated under reduced pressure. The residue and the solid collected by filtration were combined to obtain the title compound (280 mg, yield 15%).

Workup

  1. additionwere added at room temperature
  2. customAfter completion of the reaction
  3. washthe resultant mixture was washed with ethyl acetate
  4. additionDiluted hydrochloric acid was added to the water phase
  5. filtrationthe obtained solid was collected by filtration
  6. extractionExtraction with a mixed solution of ethyl acetate and tetrahydrofuran from the filtrate
  7. concentrationthe organic layer was concentrated under reduced pressure
  8. filtrationThe residue and the solid collected by filtration

Sources & evidence

ORD record
ord-65e621a028094e45bb7d8aa12bdbaf79
Source dataset
uspto-grants-2016_08
Patent number
US09403798B2

Reaction notes

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