N-methyl-2-pyrrolidone → 1-[(3-Fluoro-4-pyridinyl)amino]-3-methyl-5-(phenylmethoxy)-1H-indole

HRID 1029736Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1029736
[CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([O:11][CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH:9]=2)[N:4]([NH2:19])[CH:3]=1.CN1CCCC1=O.Cl.Cl[C:29]1[CH:34]=[CH:33][N:32]=[CH:31][C:30]=1[F:35].C(=O)(O)[O-].[Na+]>C(OCC)(=O)C>[F:35][C:30]1[CH:31]=[N:32][CH:33]=[CH:34][C:29]=1[NH:19][N:4]1[C:5]2[C:10](=[CH:9][C:8]([O:11][CH2:12][C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)=[CH:7][CH:6]=2)[C:2]([CH3:1])=[CH:3]1

Komponenten

6

Edukt 4

HCID 13387N-methyl-2-pyrrolidoneHCID 516892Sodium BicarbonateHCID 193602344-Chloro-3-fluoropyridine hydrochlorideHCID 199004803-methyl-5-(phenylmethoxy)-1H-indol-1-amine

Produkt 1

HCID 199004651-[(3-Fluoro-4-pyridinyl)amino]-3-methyl-5-(phenylmethoxy)-1H-indoleAusbeute 60,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a solution consisting of 3-methyl-5-(phenylmethoxy)-1H-indol-1-amine (4.81 g) and 1-methyl-2-pyrrolidinone (83 ml) was added 4-chloro-3-fluoro pyridine hydrochloride (3.20 g). The resulting mixture was heated at 80° C. for 2 hours. Upon cooling to room temperature, dilute aqueous sodium bicarbonate and ethyl acetate were added to the reaction mixture. The layers were separated and the aqueous phase was extracted with EtOAc (3x). The combined organic layers were washed successively with water (2x) and brine (1x), and thereafter dried (MgSO4). Filtration and concentration gave the crude product. Purification via flash column chromatography (silica gel, 50% ethyl acetate/dichloromethane) afforded 4.0 g of the desired product as a solid, m.p. 210°-213° C.

Aufarbeitung

  1. temperatureUpon cooling to room temperature
  2. customThe layers were separated
  3. extractionthe aqueous phase was extracted with EtOAc (3x)
  4. washThe combined organic layers were washed successively with water (2x) and brine (1x)
  5. dry with materialdried (MgSO4)
  6. filtrationFiltration and concentration
  7. customgave the crude product
  8. customPurification via flash column chromatography (silica gel, 50% ethyl acetate/dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-955271f5865940cca5a7f76918920b6f
Quelldatensatz
uspto-grants-1992_04
Patentnummer
US05102891

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