ethyl(E)-3-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]acrylimidate dihydrochloride → tert-butyl 4-(2-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-a]pyridin-8-yl)piperidine-1-carboxylate

HRID 546710Notes

Reaction equation

HRID 546710 reaction equation
Cl[CH2:2][CH2:3][CH2:4][CH:5]([CH:10]1[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]1)[C:6]([NH:8][NH2:9])=O.Cl.Cl.[CH3:25][O:26][C:27]1[CH:28]=[C:29](/[CH:39]=[CH:40]/[C:41](=[NH:45])OCC)[CH:30]=[CH:31][C:32]=1[N:33]1[CH:37]=[C:36]([CH3:38])[N:35]=[CH:34]1>C(O)CC>[CH3:25][O:26][C:27]1[CH:28]=[C:29](/[CH:39]=[CH:40]/[C:41]2[N:45]=[C:6]3[CH:5]([CH:10]4[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]4)[CH2:4][CH2:3][CH2:2][N:8]3[N:9]=2)[CH:30]=[CH:31][C:32]=1[N:33]1[CH:37]=[C:36]([CH3:38])[N:35]=[CH:34]1

Participants

4

Reactant 2

HCID 66838954ethyl(E)-3-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]acrylimidate dihydrochlorideHCID 66839238Tert-butyl 4-[4-chloro-1-hydrazinocarbonyl-butan-1-yl]piperidine-1-carboxylate

Product 1

HCID 66839457tert-butyl 4-(2-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-a]pyridin-8-yl)piperidine-1-carboxylateYield 35%

Reagents, catalysts & solvents 1

HCID 10311-PropanolSolvent2×

Conditions

Temperature
90 °C

Procedure

A solution of tert-butyl 4-[4-chloro-1-hydrazinocarbonyl-butan-1-yl]piperidine-1-carboxylate (663 mg) in 1-propanol (4 mL) was added to a solution of ethyl (E)-3-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]acrylimidate dihydrochloride obtained in Example 1 (792 mg) and TEA (1.7 mL) in 1-propanol (16 mL), and the reaction solution was stirred at 90° C. overnight. The reaction solution was left to cool to room temperature and then concentrated under reduced pressure. Ethyl acetate, water and a saturated sodium bicarbonate solution were added to the concentration residue, and the organic layer was separated. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (carrier: Chromatorex™ NH; elution solvent: heptane-ethyl acetate system) to obtain 361 mg of the title compound. The property value of the compound is as follows.

Workup

  1. waitThe reaction solution was left
  2. temperatureto cool to room temperature
  3. concentrationconcentrated under reduced pressure
  4. additionEthyl acetate, water and a saturated sodium bicarbonate solution were added to the concentration residue
  5. customthe organic layer was separated
  6. washThe organic layer was washed with brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting residue was purified by silica gel column chromatography (carrier: Chromatorex™ NH; elution solvent: heptane-ethyl acetate system)

Sources & evidence

ORD record
ord-d8bbd2e3073041d5a1d69328cb008916
Source dataset
uspto-grants-2011_05
Patent number
US07935815B2

Reaction notes

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