Hydrochloric Acid → HCID 178480544, compound

HRID 1464313Notes

Reaction equation

HRID 1464313 reaction equation
[OH-:1].[K+].[CH2:3]([N:10]1[CH2:15][CH2:14][N:13]([C:16]2[N:21]=[C:20]([C:22](OCC)=[O:23])[C:19]([C:27]([O:29]CC)=O)=[CH:18]N=2)[CH2:12][CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl.C([N:35](CC)CC)C.S(Cl)(Cl)=O.[CH3:44][NH2:45].C([O-])(=O)C.[Na+].C(OC(=O)C)(=O)C>CO.O.C(O)C>[CH3:44][N:45]1[CH:18]=[C:19]([C:27]([OH:29])=[O:1])[C:20]([C:22](=[NH:35])[OH:23])=[N:21][CH:16]1[N:13]1[CH2:14][CH2:15][N:10]([CH2:3][C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH2:11][CH2:12]1

Participants

12

Reactant 8

HCID 313Hydrochloric AcidHCID 6329MethylamineHCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 14797Potassium HydroxideHCID 24386Thionyl ChlorideHCID 517045Sodium AcetateHCID 13769871HCID 13769871, compound

Product 1

HCID 178480544HCID 178480544, compoundYield 56%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Potassium hydroxide (8.4 g; 150 mmoles), 50 ml of ethanol and 10 ml of water were added to 19.9 g (50 mmoles) of diethyl 2-(4-benzylpiperazino)-4,5-pyrimidinedicarboxylate, and the mixture was stirred for 1 hour at room temperature and then for 2 hours at 40 ° C. Hydrochloric acid was added to the solution to adjust its pH to 3. The resulting crystals were separated by filtration, and washed with ethyl acetate. The crystals (18.1 g) were dissolved in 527 ml of methylene chloride, and 21.3 g (211 mmoles) of triethylamine and 12.5 g (105 mmoles) of thionyl chloride were added. The mixture was stirred at room temperature for 1 hour, and then cooled to -78 ° C. 8.17 g (105 mmoles) of a 40% methanol solution of methylamine was added, and the temperature was raised to room temperature. The mixture was stirred at this temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and the resulting solid was washed with water. To 14.4 g of the solid were added 3.32 g (40.4 mmoles) of sodium acetate and 41.3 g (404 mmoles) of acetic anhydride were added. The mixture was heated under reflux for 2 hours. The reaction mixture was concentrated under reduced pressure, and after adding water, the mixture was stirred for 30 minutes. The resulting solid was purified by silica gel column chromatography to give 9.72 g (yield 56%) of the desired compound.

Workup

  1. waitfor 2 hours at 40 ° C
  2. customThe resulting crystals were separated by filtration
  3. washwashed with ethyl acetate
  4. dissolutionThe crystals (18.1 g) were dissolved in 527 ml of methylene chloride
  5. stirringThe mixture was stirred at room temperature for 1 hour
  6. temperaturecooled to -78 ° C
  7. temperaturethe temperature was raised to room temperature
  8. stirringThe mixture was stirred at this temperature for 1 hour
  9. concentrationThe reaction mixture was concentrated under reduced pressure
  10. washthe resulting solid was washed with water
  11. additionwere added
  12. temperatureThe mixture was heated
  13. temperatureunder reflux for 2 hours
  14. concentrationThe reaction mixture was concentrated under reduced pressure
  15. additionafter adding water
  16. stirringthe mixture was stirred for 30 minutes
  17. customThe resulting solid was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-0f159b2e7d0b4448a9e2ca092797a5d9
Source dataset
uspto-grants-1994_04
Patent number
US05304555

Reaction notes

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