Benzaldehyde → racemic 8-(1-benzylpiperidin-4-yl)-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 546713Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 546713
[CH:1](=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:9][O:10][C:11]1[CH:12]=[C:13](/[CH:23]=[CH:24]/[C:25]2[N:39]=[C:28]3[CH:29]([CH:33]4[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]4)[CH2:30][CH2:31][CH2:32][N:27]3[N:26]=2)[CH:14]=[CH:15][C:16]=1[N:17]1[CH:21]=[C:20]([CH3:22])[N:19]=[CH:18]1.[Na].C(=O)(O)[O-].[Na+]>C1COCC1.C(OCC)(=O)C.C(O)(=O)C>[CH2:1]([N:36]1[CH2:37][CH2:38][CH:33]([CH:29]2[CH2:30][CH2:31][CH2:32][N:27]3[N:26]=[C:25](/[CH:24]=[CH:23]/[C:13]4[CH:14]=[CH:15][C:16]([N:17]5[CH:21]=[C:20]([CH3:22])[N:19]=[CH:18]5)=[C:11]([O:10][CH3:9])[CH:12]=4)[N:39]=[C:28]23)[CH2:34][CH2:35]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Komponenten

8

Edukt 4

HCID 240BenzaldehydeHCID 516892Sodium BicarbonateHCID 5360545SodiumHCID 668394842-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-8-(piperidin-4-yl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-a]pyridine

Produkt 1

HCID 66839015racemic 8-(1-benzylpiperidin-4-yl)-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

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 176Acetic AcidLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

Benzaldehyde (15 μl) and glacial acetic acid (16 μl) were added to a solution of racemic 2-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-8-(piperidin-4-yl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-a]pyridine obtained in Examples 118 and 119 (30 mg) in THF (2 ml), and the reaction solution was stirred at room temperature for 30 minutes. Sodium triacetoxyhydroborate (46 mg) was added to the reaction solution, and the reaction solution was stirred at room temperature for four hours. A saturated sodium bicarbonate solution and ethyl acetate 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 concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (carrier: Chromatorex™ NH; elution solvent: ethyl acetate) to obtain 27 mg of racemic 8-(1-benzylpiperidin-4-yl)-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: 50% ethanol-hexane) to obtain the title optically active compound with a retention time of 14 minutes and positive optical rotation (9.4 mg; >99% ee) and the title optically active compound with a retention time of 20 minutes and negative optical rotation (8.9 mg; 99% ee).

Aufarbeitung

  1. stirringthe reaction solution was stirred at room temperature for four hours
  2. customthe organic layer was separated
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography (carrier: Chromatorex™ NH; elution solvent: ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-c095053b9bb34696a08b5dc17f7e087d
Quelldatensatz
uspto-grants-2011_05
Patentnummer
US07935815B2

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