Hydrochloric Acid → 2-pyrimidin-4-yl-7,8,9,10-tetrahydro-6H-pyrimido[1,2-a]azepin-4-one

HRID 1520418Notes

Reaction equation

HRID 1520418 reaction equation
[N:1]1[CH2:2][CH:3]=[CH:4][CH:5]=[CH:6][C:7]=1[NH2:8].Cl.C(=O)([O-])[O-].[K+].[K+].[N:16]1[CH:21]=[CH:20][C:19]([C:22](=O)[CH2:23][C:24](OCC)=[O:25])=[N:18][CH:17]=1>C(O)C>[N:16]1[CH:21]=[CH:20][C:19]([C:22]2[N:8]=[C:7]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][N:1]3[C:24](=[O:25])[CH:23]=2)=[N:18][CH:17]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 11961458Ethyl 3-oxo-3-(pyrimidin-4-yl)propanoateHCID 188006272H-azepin-7-amine

Product 1

HCID 671776292-pyrimidin-4-yl-7,8,9,10-tetrahydro-6H-pyrimido[1,2-a]azepin-4-oneYield 28.7%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a suspension of 77.9 g (524.1 mmol) of 2H-azepin-7-amine, 3,4,5,6-tetrahydro, monohydrochloride (synthesis as described in WO96/14844 or in Journal of Medicinal Chemistry (1998), 41(9), 1361-1366) in 390 mL of ethanol was added 72.4 g (524.1 mmol) of potassium carbonate. The reaction mixture was stirred at room temperature for 10 min, 101.7 g (524.1 mmol) of ethyl 3-(4-pyrimidinyl)-3-oxopropionate was added and the resulting mixture was stirred under reflux for 16 h. The cooled solution was evaporated to remove solvent. The mixture was dissolved in dichloromethane, washed with a saturated aqueous solution of sodium chloride, dried over sodium sulfate and evaporated to dryness. The residue was filtrate through a pad of silica, rinsing with dichloromethane and then ethyl acetate. After evaporation, the resulting solid was triturated in diethyl ether, filtrated to afford 36.4 g (28%) of the desired compound as a white-brown powder.

Workup

  1. customsynthesis
  2. stirringthe resulting mixture was stirred
  3. temperatureunder reflux for 16 h
  4. customThe cooled solution was evaporated
  5. customto remove solvent
  6. dissolutionThe mixture was dissolved in dichloromethane
  7. washwashed with a saturated aqueous solution of sodium chloride
  8. dry with materialdried over sodium sulfate
  9. customevaporated to dryness
  10. washrinsing with dichloromethane
  11. customAfter evaporation
  12. customthe resulting solid was triturated in diethyl ether
  13. filtrationfiltrated

Sources & evidence

ORD record
ord-8dc44d035d2c4047a886e25d4029f5d8
Source dataset
uspto-grants-2015_07
Patent number
US09073914B2

Reaction notes

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