Phosphorus oxychloride → HCID 71534484, Verbindung

HRID 1523734Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1523734
[CH:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([C:13]([NH:15][NH2:16])=[O:14])=[N:5]1)([CH3:3])[CH3:2].Cl.[CH:18]1([N:22]2[CH2:27][CH2:26][CH:25]([CH2:28][C:29](O)=O)[CH2:24][CH2:23]2)[CH2:21][CH2:20][CH2:19]1.P(Cl)(Cl)(Cl)=O>>[CH:18]1([N:22]2[CH2:23][CH2:24][CH:25]([CH2:28][C:29]3[O:14][C:13]([C:6]4[C:7]5[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=5)[N:4]([CH:1]([CH3:3])[CH3:2])[N:5]=4)=[N:15][N:16]=3)[CH2:26][CH2:27]2)[CH2:19][CH2:20][CH2:21]1

Komponenten

4

Edukt 3

HCID 24813Phosphorus oxychlorideHCID 86724908HCID 86724908, VerbindungHCID 86724919HCID 86724919, Verbindung

Produkt 1

HCID 71534484HCID 71534484, VerbindungAusbeute 30 %

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To the mixture of 1-isopropyl-1H-indazole-3-carboxylic acid hydrazide (120 mg, 0.55 mmol) and (1-cyclobutyl piperidin-4-yl) acetic acid hydrochloride (147 mg, 0.74 mmol, obtained in preparation 6) cooled at 0° C., was added phosphoryl chloride (1.5 mL). The reaction temperature was gradually raised to 100° C. and stirred was 2 hours. Upon completion of the reaction, it was cooled to 0° C. and triturated with hexanes (3×25 mL). The crude product was cooled to 0° C., basified with aqueous sodium hydroxide solution and extracted with 5% methanol in dichloromethane. The combined organic layer was dried over anhydrous sodium sulphate and the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography to obtain 3-[5-(1-cyclobutyl piperidin-4-yl methyl)-[1,3,4]oxadiazol-2-yl]-1-isopropyl-1H-indazole (62 mg)

Aufarbeitung

  1. temperatureThe reaction temperature was gradually raised to 100° C.
  2. customUpon completion of the reaction, it
  3. temperaturewas cooled to 0° C.
  4. customtriturated with hexanes (3×25 mL)
  5. temperatureThe crude product was cooled to 0° C.
  6. extractionextracted with 5% methanol in dichloromethane
  7. dry with materialThe combined organic layer was dried over anhydrous sodium sulphate
  8. customthe solvent was removed under reduced pressure
  9. customThe crude product was purified by silica gel column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-8a8c841d850245b3a9871b4159ef359a
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09079894B2

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