Ammonia → 5-chloro-3-(2,6-difluoro-pyridin-3-ylmethyl)-1H-pyrrolo[2,3-b]pyridine

HRID 1024245Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1024245
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[N:3]=1.C([Li])CCC.C([Cu])#N.C(OC([N:24]1[C:28]2=[N:29][CH:30]=[C:31]([Cl:33])[CH:32]=[C:27]2[C:26]([CH2:34]Cl)=[CH:25]1)=O)(C)(C)C.N>O1CCCC1.CCCCCC.O>[Cl:33][C:31]1[CH:32]=[C:27]2[C:26]([CH2:34][C:7]3[C:2]([F:1])=[N:3][C:4]([F:8])=[CH:5][CH:6]=3)=[CH:25][NH:24][C:28]2=[N:29][CH:30]=1

Komponenten

9

Edukt 5

HCID 222AmmoniaHCID 739342,6-DifluoropyridineHCID 576192411-Boc-5-chloro-3-(chloromethyl)-7-azaindoleHCID 178418339ButyllithiumHCID 178418546HCID 178418546, Verbindung

Produkt 1

HCID 576193535-chloro-3-(2,6-difluoro-pyridin-3-ylmethyl)-1H-pyrrolo[2,3-b]pyridine

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel3×HCID 8058HexaneLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To 2,6-Difluoropyridine (58, 3.40 g, 0.0295 mol) in tetrahydrofuran (200.0 mL), under an atmosphere of nitrogen at −78° C., 2.50M of n-butyllithium in hexane (12.0 mL) was added slowly. After 60 minutes, CuCN.2LiCl (0.75M in tetrahydrofuran, 40.0 mL) was added to the reaction mixture. After 5 minutes, 5-chloro-3-chloromethyl-pyrrolo[2,3-b]pyridine-1-carboxylic acid tert-butyl ester (535, 4.20 g, 0.0139 mol, prepared as described in Example 49, Scheme 164) in tetrahydrofuran (20 mL) was added to the reaction. The reaction was stirred at −78° C. overnight, then poured into water and ammonia (10 mL), and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 15% ethyl acetate in hexane to give a white solid (P-0155, 300 mg, 7.7%). MS (ESI) [M−H+]−=278.1.

Aufarbeitung

  1. waitAfter 5 minutes
  2. extractionextracted with ethyl acetate
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated
  6. custompurified by silica gel column chromatography
  7. washeluting with 15% ethyl acetate in hexane
  8. customto give a white solid (P-0155, 300 mg, 7.7%)

Quellen und Nachweise

ORD-Eintrag
ord-802938af14254143ae292d683b8811a4
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08722702B2

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