Acetohydrazide → (E)-2-(4-((2-(4-fluoro-2-methylphenyl)-6-methoxybenzo[b]thiophen-3-yl)oxy)styryl)-5-methyl-1,3,4-oxadiazole

HRID 632632Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 632632
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]3[CH:13]=[C:14]([O:17][CH3:18])[CH:15]=[CH:16][C:10]=3[C:9]=2[O:19][C:20]2[CH:25]=[CH:24][C:23](/[CH:26]=[CH:27]/[C:28]([OH:30])=O)=[CH:22][CH:21]=2)=[C:4]([CH3:31])[CH:3]=1.[C:32]([NH:35][NH2:36])(=O)[CH3:33].O=P(Cl)(Cl)Cl>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]3[CH:13]=[C:14]([O:17][CH3:18])[CH:15]=[CH:16][C:10]=3[C:9]=2[O:19][C:20]2[CH:21]=[CH:22][C:23](/[CH:26]=[CH:27]/[C:28]3[O:30][C:32]([CH3:33])=[N:35][N:36]=3)=[CH:24][CH:25]=2)=[C:4]([CH3:31])[CH:3]=1

Komponenten

4

Edukt 3

HCID 14039AcetohydrazideHCID 24813Phosphorus oxychlorideHCID 86730646(E)-3-(4-((2-(4-fluoro-2-methylphenyl)-6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid

Produkt 1

HCID 86730645(E)-2-(4-((2-(4-fluoro-2-methylphenyl)-6-methoxybenzo[b]thiophen-3-yl)oxy)styryl)-5-methyl-1,3,4-oxadiazoleAusbeute 76,5 %

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a 30 mL vial, (E)-3-(4-((2-(4-fluoro-2-methylphenyl)-6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid (100 mg, 0.230 mmol) and acetohydrazide (85 mg, 1.151 mmol) were dissolved in POCl3 (2 mL, 21.46 mmol) and the mixture was heated to 100° C. for 18 h. The reaction mixture was cooled to room temperature poured into ice. The solution was quenched with sat. sodium bicarb and diluted with DCM. The organic layer was collected (phase separator) and concentrated to provide the crude material. The crude product was purified by reverse phase HPLC (acidic condition, 0.1% TFA in 30-100% CH3CN/H2O) to afford (E)-2-(4-((2-(4-fluoro-2-methylphenyl)-6-methoxybenzo[b]thiophen-3-yl)oxy)styryl)-5-methyl-1,3,4-oxadiazole (83 mg, 0.176 mmol, 76% yield) as a white solid. 1H NMR (400 MHz, CD3OD) δ ppm=2.38 (s, 3 H), 2.57 (s, 3 H), 3.90 (s, 3 H), 6.81-6.98 (m, 4 H), 6.98-7.08 (m, 2 H), 7.28-7.42 (m, 2 H), 7.44-7.58 (m, 4 H), LC/MS (m/z, MH+): 473.4.

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to room temperature
  2. additionpoured into ice
  3. customThe solution was quenched with sat. sodium bicarb
  4. additiondiluted with DCM
  5. customThe organic layer was collected (phase separator)
  6. concentrationconcentrated
  7. customto provide the crude material
  8. customThe crude product was purified by reverse phase HPLC (acidic condition, 0.1% TFA in 30-100% CH3CN/H2O)

Quellen und Nachweise

ORD-Eintrag
ord-bf980b5bb15f4870ba1d2362bc168b34
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09321746B2

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