Pyridine → N-[4-(3-cyano-1-ethyl-6-methoxy-1H-indol-2-ylethynyl)-phenyl]-dimethylphosphinic amide

HRID 252535Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 252535
N[C:2]1[CH:3]=[C:4]([C:8]#[C:9][C:10]2[N:11]([CH2:23][CH3:24])[C:12]3[C:17]([C:18]=2[C:19]#[N:20])=[CH:16][CH:15]=[C:14]([O:21][CH3:22])[CH:13]=3)[CH:5]=[CH:6][CH:7]=1.[CH3:25][P:26](Cl)([CH3:28])=[O:27].[N:30]1C=CC=CC=1>C1COCC1.CCOC(C)=O>[C:19]([C:18]1[C:17]2[C:12](=[CH:13][C:14]([O:21][CH3:22])=[CH:15][CH:16]=2)[N:11]([CH2:23][CH3:24])[C:10]=1[C:9]#[C:8][C:4]1[CH:5]=[CH:6][C:7]([NH:30][P:26]([CH3:28])([CH3:25])=[O:27])=[CH:2][CH:3]=1)#[N:20]

Komponenten

6

Edukt 3

HCID 1049PyridineHCID 517954Dimethylphosphinic chlorideHCID 59425363HCID 59425363, Verbindung

Produkt 1

HCID 66866278N-[4-(3-cyano-1-ethyl-6-methoxy-1H-indol-2-ylethynyl)-phenyl]-dimethylphosphinic amideAusbeute 52 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

2-(3-Aminophenylethynyl)-1-ethyl-6-methoxy-1H-indole-3-carbonitrile (100 mg, 0.32 mmol), prepared as described in Example 1H, is dissolved in pyridine (300 μL) at 0° C. Dimethylphosphinic chloride (60 mg, 0.53 mmol) in THF (300 μL) is added. The reaction is stirred at room temperature for 2 hours. The reaction mixture is diluted in EtOAc, and is washed with aqueous HCl followed by brine. The organic layer is dried and concentrated. Purification by silica chromatography (acetone) yields N-[4-(3-cyano-1-ethyl-6-methoxy-1H-indol-2-ylethynyl)-phenyl]-dimethylphosphinic amide (65 mg, 52%), compound 227, as a pure white solid. The silica column is then flushed with 9/1 CH2Cl2/MeOH to yield 9 mg of N-[4-(3-cyano-1-ethyl-6-methoxy-1H-indol-2-ylethynyl)-phenyl]-bis-(dimethylphosphinic)amide as a by-product.

Aufarbeitung

  1. washis washed with aqueous HCl
  2. customThe organic layer is dried
  3. concentrationconcentrated
  4. customPurification by silica chromatography (acetone)

Quellen und Nachweise

ORD-Eintrag
ord-297be9d137414704b06e2cf119d53dca
Quelldatensatz
uspto-grants-2011_01
Patentnummer
US07868037B2

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