Formamidine acetate → 5,6,7,8-Tetrahydro-7-(phenylmethyl)pyrido(3,4-d)pyrimidin-4(3H)-one

HRID 586706Notes

Reaction equation

HRID 586706 reaction equation
[Na].Cl.C([O:5][C:6]([CH:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:10][C:9]1=O)=O)C.C(O)(=O)C.[CH:26]([NH2:28])=[NH:27]>C(O)C>[CH2:14]([N:11]1[CH2:12][CH2:13][C:8]2[C:6](=[O:5])[NH:28][CH:26]=[N:27][C:9]=2[CH2:10]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

5

Reactant 3

HCID 160693Formamidine acetateHCID 2723880Ethyl 1-benzyl-3-oxopiperidine-4-carboxylate hydrochlorideHCID 5360545Sodium

Product 1

HCID 1357235075,6,7,8-Tetrahydro-7-(phenylmethyl)pyrido(3,4-d)pyrimidin-4(3H)-oneYield 70%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Sodium metal (10.1 g, 0.44 mol) was added to ethanol (520 mL) and stirred at room temperature under nitrogen gas until a clear solution had formed. Ethyl-3-oxo-N-benzylpiperidine-4-carboxylate hydrochloride (56.5 g, 0.19 mol) and formamidine acetate (22.9 g, 0.22 mol) were then added and the reaction mixture heated under reflux for 40 hours. The reaction mixture was concentrated under reduced pressure, and the residue partitioned between water (400 mL) and dichloromethane (400 mL). The aqueous phase was re-extracted with dichloromethane (2×100 mL). The combined organic extracts were dried (MgSO4) and concentrated under reduced pressure. The resulting solid was triturated with diethyl ether (100 mL) and the product collected by filtration to give the title compound as a light brown solid (32.0 g, 70%).

Workup

  1. customhad formed
  2. temperaturethe reaction mixture heated
  3. temperatureunder reflux for 40 hours
  4. concentrationThe reaction mixture was concentrated under reduced pressure
  5. customthe residue partitioned between water (400 mL) and dichloromethane (400 mL)
  6. extractionThe aqueous phase was re-extracted with dichloromethane (2×100 mL)
  7. dry with materialThe combined organic extracts were dried (MgSO4)
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting solid was triturated with diethyl ether (100 mL)
  10. filtrationthe product collected by filtration

Sources & evidence

ORD record
ord-e27e5c93189a4d98af6a085630d29e73
Source dataset
uspto-grants-2005_08
Patent number
US06936619B2

Reaction notes

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