Water → racemic 8-cyclopropyl-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 546695ノート

反応式

HRID 546695 の反応式
Cl[CH2:2][CH2:3][CH2:4][CH:5]([CH:10]1[CH2:12][CH2:11]1)[C:6]([NH:8][NH2:9])=O.Cl.Cl.[CH3:15][O:16][C:17]1[CH:18]=[C:19](/[CH:29]=[CH:30]/[C:31](=[NH:35])OCC)[CH:20]=[CH:21][C:22]=1[N:23]1[CH:27]=[C:26]([CH3:28])[N:25]=[CH:24]1.C(OCC)(=O)C.O>C(O)C>[CH:10]1([CH:5]2[CH2:4][CH2:3][CH2:2][N:8]3[N:9]=[C:31](/[CH:30]=[CH:29]/[C:19]4[CH:20]=[CH:21][C:22]([N:23]5[CH:27]=[C:26]([CH3:28])[N:25]=[CH:24]5)=[C:17]([O:16][CH3:15])[CH:18]=4)[N:35]=[C:6]23)[CH2:12][CH2:11]1

参加物

6

反応物 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 66838954ethyl(E)-3-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]acrylimidate dihydrochlorideHCID 668394715-Chloro-2-cyclopropyl-valeric acid hydrazide

生成物 1

HCID 66839147racemic 8-cyclopropyl-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収率 17.5%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒2 回

反応条件

温度
70 °C

実験手順

A solution of 5-chloro-2-cyclopropyl-valeric acid hydrazide (125 mg) in ethanol (1.5 mL) was added to a solution of ethyl (E)-3-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]acrylimidate dihydrochloride (259 mg) and TEA (0.46 ml) in ethanol (3 ml), and the reaction solution was stirred at 70° C. for 22 hours. 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 43 mg of racemic 8-cyclopropyl-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 28 minutes and negative optical rotation (16.4 mg; 100% ee) and the title optically active compound with a retention time of 49 minutes and positive optical rotation (16.3 mg; 99% ee).

後処理

  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)

出典と根拠

ORDレコード
ord-38d82186bd7048638e889af43a52d9c0
出典データセット
uspto-grants-2011_05
特許番号
US07935815B2

反応ノート

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