Sodium hydride → HCID 13210503, compound

HRID 1462236Notes

Reaction equation

HRID 1462236 reaction equation
[H-].[Na+].[CH2:3]([N:10]1[CH2:15][CH2:14][N:13]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([NH:23][C:24]3[N:29]=[CH:28][CH:27]=[CH:26][N:25]=3)=[CH:19][CH:18]=2)[C:12](=[O:30])[C:11]1=[O:31])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[C:32]([O:38][CH2:39]Cl)(=[O:37])[C:33]([CH3:36])([CH3:35])[CH3:34]>CN(C)C=O>[CH2:3]([N:10]1[CH2:15][CH2:14][N:13]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([N:23]([CH2:39][O:38][C:32](=[O:37])[C:33]([CH3:36])([CH3:35])[CH3:34])[C:24]3[N:25]=[CH:26][CH:27]=[CH:28][N:29]=3)=[CH:19][CH:18]=2)[C:12](=[O:30])[C:11]1=[O:31])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 87885Chloromethyl pivalateHCID 30602472,3-Piperazinedione, 1-(phenylmethyl)-4-((4-(2-pyrimidinylamino)phenyl)methyl)-

Product 1

HCID 13210503HCID 13210503, compoundYield 64.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a mixture of 372 mg of sodium hydride (purity 50%) and 30 ml of N,N-dimethylformamide was added dropwise a solution of 3 g of 1-benzyl-4-[4-(2-pyrimidinylamino)benzyl]-2,3-dioxopiperazine in 20 ml of N,N-dimethylformamide with stirring over 30 min., after which the resulting mixture was subjected to reaction at 60° to 70° C. for one hour. After the completion of the reaction, 1.3 g of pivaloyloxymethyl chloride was dropped thereinto over 10 min. at the same temperature. After the completion of the dropwise addition, the resulting mixture was subjected to reaction at 70° to 80° C. for 30 min. After the completion of the reaction, the solvent was removed by distillation under reduced pressure, and the residue thus obtained was extracted with 100 ml of chloroform. The chloroform layer was washed with 30 ml of water and 40 ml of saturated aqueous sodium chloride solution in this order, and dried over anhydrous magnesium sulfate, after which the solvent was removed by distillation under reduced pressure. The residue thus obtained was purified by column chromatography (Wakogel C-200, eluted with chloroform), and then recrystallized from ethyl acetate-diisopropyl ether, to obtain 2.5 g (64.3% yield) of 1-benzyl-4-{4-[N-pivaloyloxymethyl-N-(2-pyrimidinyl)amino]benzyl}-2,3-dioxopiperazine having a melting point of 144° to 146° C.

Workup

  1. customafter which the resulting mixture was subjected to reaction at 60° to 70° C. for one hour
  2. additionwas dropped
  3. waitover 10 min. at the same temperature
  4. additionAfter the completion of the dropwise addition
  5. customthe resulting mixture was subjected to reaction at 70° to 80° C. for 30 min
  6. customAfter the completion of the reaction
  7. customthe solvent was removed by distillation under reduced pressure
  8. customthe residue thus obtained
  9. extractionwas extracted with 100 ml of chloroform
  10. washThe chloroform layer was washed with 30 ml of water and 40 ml of saturated aqueous sodium chloride solution in this order
  11. dry with materialdried over anhydrous magnesium sulfate
  12. customafter which the solvent was removed by distillation under reduced pressure
  13. customThe residue thus obtained
  14. customwas purified by column chromatography (Wakogel C-200, eluted with chloroform)
  15. customrecrystallized from ethyl acetate-diisopropyl ether

Sources & evidence

ORD record
ord-c92f8ae6bc064a59bde1fe992f23a11c
Source dataset
uspto-grants-1984_07
Patent number
US04459407

Reaction notes

Loading…