Potassium Carbonate → 4-allyl-2-{4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl}-5-(3-pyridyl)-1,2,4-triazol-3(2H,4H)-one

HRID 1952760Notes

Reaction equation

HRID 1952760 reaction equation
[CH2:1]([N:4]1[C:8]([C:9]2[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=2)=[N:7][N:6]([CH2:15][CH2:16][CH2:17][CH2:18]Cl)[C:5]1=[O:20])[CH:2]=[CH2:3].Cl.[CH3:22][O:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[N:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1.C(=O)([O-])[O-].[K+].[K+]>[I-].[K+].C1(C)C=CC=CC=1>[CH2:1]([N:4]1[C:8]([C:9]2[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=2)=[N:7][N:6]([CH2:15][CH2:16][CH2:17][CH2:18][N:33]2[CH2:32][CH2:31][N:30]([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=3[O:23][CH3:22])[CH2:35][CH2:34]2)[C:5]1=[O:20])[CH:2]=[CH2:3]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 9899402N-(2-Methoxyphenyl)piperazine hydrochloride2×HCID 232999794-allyl-2-(4-chlorobutyl)-5-(3-pyridyl)-1,2,4-triazol-3(2H,4H)-one

Product 1

HCID 232999864-allyl-2-{4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl}-5-(3-pyridyl)-1,2,4-triazol-3(2H,4H)-oneYield 22.2%

Reagents, catalysts & solvents 2

HCID 4875Potassium IodideCatalystHCID 1140TolueneSolvent

Conditions

Temperature
92.5 °C

Procedure

A mixture of 4-allyl-2-(4-chlorobutyl)-5-(3-pyridyl)-1,2,4-triazol-3(2H,4H)-one (3 g), 1-(2-methoxyphenyl)piperazine monohydrochloride (2.3 g), potassium carbonate (2.76 g), potassium iodide (10 mg) and toluene (100 ml) was stirred at 90-95° C. under nitrogen for 85 hours. During this time, three further portions of 1-(2-methoxyphenyl)piperazine monohydrochloride (3×1.92 g) were added at 17 hourly intervals. The solvent was removed in vacuo, the residue was diluted with water (100 ml), and the product was extracted into ethyl acetate (3×50 ml). The extracts were dried (MgSO4) and the solvent removed in vacuo to leave an oil which was purified by flash chromatography over silica using a 1:1 mixture of ether and methanol as eluant. Appropriate fractions were combined and the solvents removed in vacuo. The residue was triturated with ether, undissolved solid was removed by filtration, and the solvent was removed in vacuo. The residue was triturated with petroleum ether (b.p. 40-60° C.) and the resulting solid was collected by filtration and dried in vacuo at ambient temperature to give 4-allyl-2-{4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl}-5-(3-pyridyl)-1,2,4-triazol-3(2H,4H)-one as an off-white solid (1 g), m.p. 71-75° C.

Workup

  1. customThe solvent was removed in vacuo
  2. additionthe residue was diluted with water (100 ml)
  3. extractionthe product was extracted into ethyl acetate (3×50 ml)
  4. dry with materialThe extracts were dried (MgSO4)
  5. customthe solvent removed in vacuo
  6. customto leave an oil which
  7. customwas purified by flash chromatography over silica using
  8. additiona 1:1 mixture of ether and methanol as eluant
  9. customthe solvents removed in vacuo
  10. customThe residue was triturated with ether, undissolved solid
  11. customwas removed by filtration
  12. customthe solvent was removed in vacuo
  13. customThe residue was triturated with petroleum ether (b.p. 40-60° C.)
  14. filtrationthe resulting solid was collected by filtration
  15. customdried in vacuo at ambient temperature

Sources & evidence

ORD record
ord-0d669ddc9bdb4e07a94070d15b7b944c
Source dataset
uspto-grants-2000_09
Patent number
US06114334

Reaction notes

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