1,1'-Carbonyldiimidazole → 6-[2-[4-(Diphenylmethyl)piperazino-carbonyloxyl]ethoxy][1,2,4]triazolo[1,5-b]pyridazine

HRID 1067504Notes

Reaction equation

HRID 1067504 reaction equation
[OH:1][CH2:2][CH2:3][O:4][C:5]1[CH:6]=[CH:7][C:8]2[N:9]([N:11]=[CH:12][N:13]=2)[N:10]=1.[C:14](N1C=CN=C1)(N1C=CN=C1)=[O:15].[C:26]1([CH:32]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[N:33]2[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]2)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C(N(C(C)C)C(C)C)C>O1CCCC1>[C:39]1([CH:32]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[N:33]2[CH2:34][CH2:35][NH:36][CH:37]([C:14]([O:1][CH2:2][CH2:3][O:4][C:5]3[CH:6]=[CH:7][C:8]4[N:9]([N:11]=[CH:12][N:13]=4)[N:10]=3)=[O:15])[CH2:38]2)[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 70048BenzhydrylpiperazineHCID 81531DiisopropylethylamineHCID 229892366-(2-Hydroxyethoxy)[1,2,4]triazolo[1,5-b]pyridazine

Product 1

HCID 702352096-[2-[4-(Diphenylmethyl)piperazino-carbonyloxyl]ethoxy][1,2,4]triazolo[1,5-b]pyridazineYield 40.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

6-(2-Hydroxyethoxy)[1,2,4]triazolo[1,5-b]pyridazine (450 mg) was dissolved in tetrahydrofuran (20 ml), followed by addition of carbonyldiimidazole (649 mg). The mixture was stirred at room temperature for 3 hours, followed by addition of 1-(diphenylmethyl)piperazine (1.07 g) and N-ethyldiisopropylamine (0.73 ml). The mixture was stirred at 60° C. for 17 hours and concentrated under reduced pressure. Ice-water was added to the residue, followed by extraction with ethyl acetate. The extract was washed with an aqueous sodium chloride saturated solution, dried over magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica-gel column chromatography and eluted with a mixture of ethyl acetate and hexane (1:1). Fractions containing the objective compound were collected and concentrated. The resulting crystals were recrystalized from ethyl acetate to yield the title compound (464 mg).

Workup

  1. stirringThe mixture was stirred at 60° C. for 17 hours
  2. concentrationconcentrated under reduced pressure
  3. additionIce-water was added to the residue
  4. extractionfollowed by extraction with ethyl acetate
  5. washThe extract was washed with an aqueous sodium chloride saturated solution
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. washeluted with a mixture of ethyl acetate and hexane (1:1)
  9. additionFractions containing the objective compound
  10. customwere collected
  11. concentrationconcentrated
  12. customThe resulting crystals were recrystalized from ethyl acetate

Sources & evidence

ORD record
ord-507fcf75b79f4f489f185d7b1fe55e7b
Source dataset
uspto-grants-2001_06
Patent number
US06248740B1

Reaction notes

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