Reaction #305074

Reaction equation

ε-caprolactam

potassium carbonate

2H-azepin-7-amine

monohydrochloride

ethyl 3-(4-pyrimidinyl)-3-oxopropionate

→

pure product

Yield 28.7%

2-Pyrimidin-4-yl-7,8,9,10-tetrahydro-6H-pyrimido[1,2-a]azepin-4-one

Yield 28.7%

Solvents

ethanol

Conditions

Workup

1. 1
   Othersynthesis
2. 2
   workup.STIRRINGthe resulting mixture was stirred
3. 3
   Temperatureunder reflux for 16 h
4. 4
   OtherThe cooled solution was evaporated
5. 5
   Otherto remove solvent
6. 6
   workup.DISSOLUTIONThe mixture was dissolved in dichloromethane
7. 7
   Washwashed with a saturated aqueous solution of sodium chloride
8. 8
   Dryingdried over sodium sulfate
9. 9
   Otherevaporated to dryness
10. 10
    Washrinsing with dichloromethane
11. 11
    OtherAfter evaporation
12. 12
    Otherthe resulting solid was triturated with diethyl ether

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 Journal of Medicinal Chemistry (1998), 41(9), 1361-1366 or by analogy with the method described in example 1, step 1.1. and 1.2 using ε-caprolactam instead of (+/−)-3-phthalimidopiperidin-2-one) 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 with diethyl ether to afford 36.4 g (28%) of pure product as a white-brown powder.

Source