Hydrochloric Acid → 9-(2-Oxo-2-phenyl-ethyl)-8-phenyl-2-(4-pyridinyl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one hydrochloride

HRID 1296429Notes

Reaction equation

HRID 1296429 reaction equation
[C:1]1([CH:7]2[CH2:23][CH2:22][N:10]3[C:11](=[O:21])[CH:12]=[C:13]([C:15]4[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=4)[N:14]=[C:9]3[NH:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].Br[CH2:27][C:28]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:29].[ClH:36]>CN(C)C=O.C(O)C.C(O)(C)C.O>[ClH:36].[O:29]=[C:28]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH2:27][N:8]1[C:9]2=[N:14][C:13]([C:15]3[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=3)=[CH:12][C:11](=[O:21])[N:10]2[CH2:22][CH2:23][CH:7]1[C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 6259Phenacyl bromideHCID 24758Sodium hydrideHCID 1357802668-Phenyl-2-(4-pyridinyl)-6,7,8,9-tetrahydro-4H-pyrimido[1.2-a]pyrimidin-4-one

Product 1

HCID 230261619-(2-Oxo-2-phenyl-ethyl)-8-phenyl-2-(4-pyridinyl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one hydrochlorideYield 39%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 3776IsopropanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 0.3 g (98 mmoles) of 8-phenyl-2-(4-pyridinyl)-6,7,8,9-tetrahydro-4H-pyrimido[1.2-a]pyrimidin-4-one in 8 ml of anhydrous dimethylformamide was treated with 51 mg (1.28 mmoles) of sodium hydride (60% in mineral oil). The resulting suspension was stirred at 0° C. for 30 mins and then treated with 0.255 g (1.28 mmoles) of 2-bromoacetophenone. After stirring for 18 h at room temperature, water was added and the reaction mixture was extracted with ethyl acetate. The organic phase was washed with a saturated solution of aqueous sodium chloride and was evaporated under reduced pressure to give crude product. Purification using silica gel chromatography eluting with a gradient comprising dichloromethane/methanol in the proportions 99/1 to 95/5 gave pure product which was dissolved in ethanol and treated with 1 equivalent of a solution of hydrochloric acid in isopropanol. The resulting salt was recrystallized from a mixture of isopropanol/diisopropylether to give 0.16 g (39%) of pure product. Mp: 134-137° C.

Workup

  1. stirringAfter stirring for 18 h at room temperature
  2. extractionthe reaction mixture was extracted with ethyl acetate
  3. washThe organic phase was washed with a saturated solution of aqueous sodium chloride
  4. customwas evaporated under reduced pressure
  5. customto give crude product
  6. customPurification
  7. washeluting with a gradient comprising dichloromethane/methanol in the proportions 99/1 to 95/5
  8. customgave pure product which
  9. customThe resulting salt was recrystallized from a mixture of isopropanol/diisopropylether

Sources & evidence

ORD record
ord-6aa86dfe852448f4b7390782d6e9520f
Source dataset
uspto-grants-2007_07
Patent number
US07247638B2

Reaction notes

Loading…