Water → racemic 8-cyclohexyl-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]pyridine

HRID 546700Notes

Reaction equation

HRID 546700 reaction equation
Cl.Cl[CH2:3][CH2:4][CH2:5][CH:6]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)[C:7]([NH:9][NH2:10])=O.Cl.Cl.[CH3:19][O:20][C:21]1[CH:22]=[C:23](/[CH:33]=[CH:34]/[C:35](=[NH:39])OCC)[CH:24]=[CH:25][C:26]=1[N:27]1[CH:31]=[C:30]([CH3:32])[N:29]=[CH:28]1.C(OCC)(=O)C.O>C(O)C>[CH:11]1([CH:6]2[CH2:5][CH2:4][CH2:3][N:9]3[N:10]=[C:35](/[CH:34]=[CH:33]/[C:23]4[CH:24]=[CH:25][C:26]([N:27]5[CH:31]=[C:30]([CH3:32])[N:29]=[CH:28]5)=[C:21]([O:20][CH3:19])[CH:22]=4)[N:39]=[C:7]23)[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1

Participants

6

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 66838954ethyl(E)-3-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]acrylimidate dihydrochlorideHCID 668394535-Chloro-2-cyclohexyl-valeric acid hydrazide hydrochloride

Product 1

HCID 66839113racemic 8-cyclohexyl-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]pyridineYield 13.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
70 °C

Procedure

A solution of 5-chloro-2-cyclohexyl-valeric acid hydrazide hydrochloride (144 mg) and TEA (0.32 ml) in ethanol (1 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 (167 mg) and TEA (0.32 ml) in ethanol (1.6 ml), and the reaction solution was stirred at 70° C. for two days. The reaction solution was left to cool to room temperature. Then, ethyl acetate and water were added to the reaction solution, 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) and again purified by silica gel column chromatography (elution solvent: ethyl acetate-methanol system) to obtain 27 mg of racemic 8-cyclohexyl-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]pyridine. Then, the racemate was separated by CHIRALPAK™ IB manufactured by Daicel Chemical Industries, Ltd. (2 cm×25 cm; mobile phase: 20% ethanol-hexane) to obtain the title optically active compound with a retention time of 16 minutes and positive optical rotation (11.0 mg; 100% ee) and the title optically active compound with a retention time of 39 minutes and negative optical rotation (10.2 mg; 100% ee).

Workup

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

Sources & evidence

ORD record
ord-0af3498b14aa48e1b4f4815ab64fb83e
Source dataset
uspto-grants-2011_05
Patent number
US07935815B2

Reaction notes

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