tert-Butyl N-(3-oxopropyl)carbamate → 1-(4-Benzylpiperazin-1-yl)tetrahydropyrimidin-2(1H)-one

HRID 20228Notes

Reaction equation

HRID 20228 reaction equation
O=[CH:2][CH2:3][CH2:4][NH:5][C:6](=[O:12])OC(C)(C)C.[CH2:13]([N:20]1[CH2:25][CH2:24][N:23]([NH2:26])[CH2:22][CH2:21]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.Cl.C(OCC)(=O)C>CO.C(OCC)(=O)C>[CH2:13]([N:20]1[CH2:21][CH2:22][N:23]([N:26]2[CH2:2][CH2:3][CH2:4][NH:5][C:6]2=[O:12])[CH2:24][CH2:25]1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

6

Reactant 3

HCID 10910051tert-Butyl N-(3-oxopropyl)carbamateHCID 121984534-Benzylpiperazin-1-amineHCID 21866389Hydrogen chloride-ethyl acetate

Product 1

HCID 672325181-(4-Benzylpiperazin-1-yl)tetrahydropyrimidin-2(1H)-oneYield 47%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of tert-butyl (3-oxopropyl)carbamate (4.2 g) and 4-benzylpiperazin-1-amine (4.6 g) in methanol (60 mL) was heated under reflux for 3 hours, and the solvent was distilled off under reduced pressure. After the residue was dissolved in methanol (60 mL), acetic acid (4.1 mL) and sodium triacetoxyborohydride (3.2 g) were added thereto, and the mixture was stirred at room temperature for 15 hours. The reaction mixture was concentrated under reduced pressure, made alkaline with 1N sodium hydroxide and potassium carbonate, and extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue obtained was dissolved in ethyl acetate (10 mL). and then a 4N hydrochloric acid-ethyl acetate solution (100 ml) was slowly added at 0° C., followed by stirring at room temperature for 5 hours. The precipitate was collected by filtration, dried, and then suspended in acetonitrile (200 mL). DBU (14.6 g) and CDI (7.8 g) were added thereto, and the mixture was heated under reflux for 15 hours. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with an aqueous sodium bicarbonate solution and extracted with dichloromethane. The extract was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by basic silica gel column chromatography (ethyl acetate), and recrystallized from diethyl ether to obtain the title compound (3.1 g, 46%) as white crystals.

Workup

  1. temperatureunder reflux for 3 hours
  2. distillationthe solvent was distilled off under reduced pressure
  3. dissolutionAfter the residue was dissolved in methanol (60 mL)
  4. additionacetic acid (4.1 mL) and sodium triacetoxyborohydride (3.2 g) were added
  5. concentrationThe reaction mixture was concentrated under reduced pressure
  6. extractionextracted with dichloromethane
  7. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  8. distillationthe solvent was distilled off under reduced pressure
  9. customThe residue obtained
  10. stirringby stirring at room temperature for 5 hours
  11. filtrationThe precipitate was collected by filtration
  12. customdried
  13. additionDBU (14.6 g) and CDI (7.8 g) were added
  14. temperaturethe mixture was heated
  15. temperatureunder reflux for 15 hours
  16. concentrationThe reaction mixture was concentrated under reduced pressure
  17. additionthe residue was diluted with an aqueous sodium bicarbonate solution
  18. extractionextracted with dichloromethane
  19. dry with materialThe extract was dried over anhydrous sodium sulfate
  20. distillationthe solvent was distilled off under reduced pressure
  21. customThe residue was purified by basic silica gel column chromatography (ethyl acetate)
  22. customrecrystallized from diethyl ether

Sources & evidence

ORD record
ord-db1e706350124ba68794ffef400c9061
Source dataset
uspto-grants-2010_06
Patent number
US07745623B2

Reaction notes

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