5-Chloro-3-ethynylpyridin-2-amine → 5-chloro-3-(5,6-dimethoxy-1-methyl-1H-indol-3-ylethynyl)pyridin-2-ylamine

HRID 490447

Reaktionsgleichung

Reaktionsgleichung von HRID 490447
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]#[CH:10])[C:5]([NH2:8])=[N:6][CH:7]=1.I[C:12]1[C:20]2[C:15](=[CH:16][C:17]([O:23][CH3:24])=[C:18]([O:21][CH3:22])[CH:19]=2)[N:14]([CH3:25])[CH:13]=1>C(N(CC)CC)C.CN(C)C=O.[Cu](I)I>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]#[C:10][C:12]2[C:20]3[C:15](=[CH:16][C:17]([O:23][CH3:24])=[C:18]([O:21][CH3:22])[CH:19]=3)[N:14]([CH3:25])[CH:13]=2)[C:5]([NH2:8])=[N:6][CH:7]=1

Komponenten

6

Edukt 2

HCID 259186675-Chloro-3-ethynylpyridin-2-amineHCID 671474473-iodo-5,6-dimethoxy-1-methyl-1H-indole

Produkt 1

HCID 671476445-chloro-3-(5,6-dimethoxy-1-methyl-1H-indol-3-ylethynyl)pyridin-2-ylamineAusbeute 68 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 83717Copper iodideKatalysatorHCID 6228DimethylformamideLösungsmittelHCID 8471TriethylamineLösungsmittel

Reaktionsbedingungen

Temperatur
20 °C

Versuchsvorschrift

A suspension of 0.43 g of 5-chloro-3-ethynylpyridin-2-ylamine, 0.6 g of 3-iodo-5,6-dimethoxy-1-methyl-1H-indole (example 103-f), and 0.072 g of copper iodide, in a mixture of 60 ml of triethylamine and 30 ml of dimethylformamide, is degassed with argon for 15 minutes. 0.066 g of bis(triphenylphosphine) palladium(II) chloride is added to the above suspension. The mixture is agitated at around 20° C. for approximately 6 hours; 0.075 g of 5-chloro-3-ethynylpyridin-2-ylamine is added and the mixture is agitated at this same temperature for 2 days. The mixture is concentrated to dryness under reduced pressure (13 kPa). The residue is taken up with 100 ml of water and extracted with three times 100 ml of dichloromethane. The organic phases are combined, dried over magnesium sulfate, filtered, and concentrated under reduced pressure (13 kPa). The residue is purified by flash chromatography on a silica column [eluent: cyclohexane/ethyl acetate (50/50 by volume)]. 0.44 g of 5-chloro-3-(5,6-dimethoxy-1-methyl-1H-indol-3-ylethynyl)pyridin-2-ylamine is thus obtained in the form of a solid, the characteristics of which are as follows:

Aufarbeitung

  1. customis degassed with argon for 15 minutes
  2. addition0.066 g of bis(triphenylphosphine) palladium(II) chloride is added to the above suspension
  3. addition0.075 g of 5-chloro-3-ethynylpyridin-2-ylamine is added
  4. stirringthe mixture is agitated at this same temperature for 2 days
  5. concentrationThe mixture is concentrated to dryness under reduced pressure (13 kPa)
  6. extractionextracted with three times 100 ml of dichloromethane
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure (13 kPa)
  10. customThe residue is purified by flash chromatography on a silica column [eluent: cyclohexane/ethyl acetate (50/50 by volume)]

Quellen und Nachweise

ORD-Eintrag
ord-4ef30a08ad3a4012b8f4af8df67b6b20
Quelldatensatz
uspto-grants-2009_05
Patentnummer
US07528147B2

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