6-Chloro-2-methyl-[1,2,4]triazolo[1,5-b]pyridazine → 6-[3-[4-(Diphenylmethoxy)piperidino]propoxy]-2-methyl[1,2,4]triazolo[1,5-b]pyridazine

HRID 1169031Notes

Reaction equation

HRID 1169031 reaction equation
[C:1]1([CH:7]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[O:8][CH:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][OH:18])[CH2:11][CH2:10]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC(C)([O-])C.[Na+].Cl[C:32]1[CH:33]=[CH:34][C:35]2[N:36]([N:38]=[C:39]([CH3:41])[N:40]=2)[N:37]=1>O1CCCC1>[C:19]1([CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[O:8][CH:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][O:18][C:32]3[CH:33]=[CH:34][C:35]4[N:36]([N:38]=[C:39]([CH3:41])[N:40]=4)[N:37]=3)[CH2:11][CH2:10]2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 122125266-Chloro-2-methyl-[1,2,4]triazolo[1,5-b]pyridazineHCID 229892644-(Diphenylmethoxy)piperidinepropanolHCID 23676156Sodium t-butoxide

Product 1

HCID 108634356-[3-[4-(Diphenylmethoxy)piperidino]propoxy]-2-methyl[1,2,4]triazolo[1,5-b]pyridazineYield 67.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

4-(Diphenylmethoxy)-1-piperidinepropanol (743 mg) was dissolved in dried tetrahydrofuran (17 ml), followed by addition of sodium t-butoxide (241 mg). The mixture was heated to 60° C. and stirred for 30 minutes. After the mixture was cooled, 6-chloro-2-methyl[1,2,4]triazolo[1,5-b]pyridazine (384 mg) was added thereto, followed by reflux under heating for 21 hours. After the mixture was cooled, ice-water was added thereto, 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, methanol and triethylamine (50:5:1). Fractions containing the objective compound were collected. The resulting crystals were washed with ethyl ether and dried to yield the title compound (700 mg).

Workup

  1. temperatureAfter the mixture was cooled
  2. temperatureby reflux
  3. temperatureunder heating for 21 hours
  4. temperatureAfter the mixture was cooled
  5. extractionfollowed by extraction with ethyl acetate
  6. washThe extract was washed with an aqueous sodium chloride saturated solution
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. washeluted with a mixture of ethyl acetate, methanol and triethylamine (50:5:1)
  10. additionFractions containing the objective compound
  11. customwere collected
  12. washThe resulting crystals were washed with ethyl ether
  13. customdried

Sources & evidence

ORD record
ord-f0251a140b2346088aa2ea9776ffb0f2
Source dataset
uspto-grants-2003_09
Patent number
US06627630B1

Reaction notes

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