N-methyl-2-pyrrolidone → HCID 22609243, compound

HRID 2306576Notes

Reaction equation

HRID 2306576 reaction equation
[CH2:1]([N:8]1[C:17](=[O:18])[C:16]2[C:11](=[CH:12][CH:13]=[C:14](Br)[CH:15]=2)[N:10]2[C:20]([N:23]3[CH2:27]CC[CH2:24]3)=[N:21][N:22]=[C:9]12)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:28][N:29]1CCCC1=O>>[CH2:1]([N:8]1[C:17](=[O:18])[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:28]#[N:29])[CH:15]=2)[N:10]2[C:20]([N:23]([CH3:27])[CH3:24])=[N:21][N:22]=[C:9]12)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

3

Reactant 2

HCID 13387N-methyl-2-pyrrolidoneHCID 22609285HCID 22609285, compound

Product 1

HCID 22609243HCID 22609243, compoundYield 90%

Procedure

In a 500 ml balloon flask, equipped with a shaker, refrigeration and nitrogen feeding, we add 10.8 g (27.1 mmol) of 4-benzyl-7-bromo-1-(pyrrolidin-1-yl)-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-one (example 164) in 100ml of N-methylpyrrolidinone (NMP). We add 4.4 g (49 mmol) of cuprous cyanide then heat the mixture, under shaking and under nitrogen for 12 hours. The solvent is eliminated by evaporation under vacuum; the residue is stirred in mixture of methylene chloride and 2N ammonia solution, the insoluble residue is eliminated by filtration, then the phases are separated by decantation. The organic phase is washed in a NaCl-saturated solution, dried on Na2SO4 and evaporated to give 24.0 g of crude product. This is purified by chromatography on silica column by elution using mixture of ethyl acetate 65/cyclohexane 35. The fractions pure in CCM are joined and evaporated under vacuum: we obtain 8.4 g of compound from example 237.

Workup

  1. customIn a 500 ml balloon flask, equipped with a shaker, refrigeration and nitrogen feeding, we
  2. temperaturethen heat the mixture
  3. customThe solvent is eliminated by evaporation under vacuum
  4. stirringthe residue is stirred in mixture of methylene chloride and 2N ammonia solution
  5. filtrationthe insoluble residue is eliminated by filtration
  6. customthe phases are separated by decantation
  7. washThe organic phase is washed in a NaCl-saturated solution
  8. customdried on Na2SO4
  9. customevaporated
  10. customto give 24.0 g of crude product
  11. customThis is purified by chromatography on silica column by elution
  12. additionmixture of ethyl acetate 65/cyclohexane 35
  13. customevaporated under vacuum

Sources & evidence

ORD record
ord-a4b1b484ae3545b491cfd16985a770dc
Source dataset
uspto-grants-2004_12
Patent number
US06828315B1

Reaction notes

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