Sodium Iodide → (R)-8-chloro-3-(2-(3-fluoropyrrolidin-1-yl)ethoxy)-1,5-naphthyridine

HRID 219243Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 219243
Cl.[F:2][C@@H:3]1[CH2:7][CH2:6][NH:5][CH2:4]1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:15][CH2:16][O:17][C:18]1[CH:19]=[N:20][C:21]2[C:26]([CH:27]=1)=[N:25][CH:24]=[CH:23][C:22]=2[Cl:28].[I-].[Na+]>CN(C=O)C>[Cl:28][C:22]1[CH:23]=[CH:24][N:25]=[C:26]2[C:21]=1[N:20]=[CH:19][C:18]([O:17][CH2:16][CH2:15][N:5]1[CH2:6][CH2:7][C@@H:3]([F:2])[CH2:4]1)=[CH:27]2

Komponenten

6

Edukt 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 2759162(3R)-3-fluoropyrrolidine hydrochlorideHCID 576909903-(2-Bromoethoxy)-8-chloro-1,5-naphthyridine

Produkt 1

HCID 57690911(R)-8-chloro-3-(2-(3-fluoropyrrolidin-1-yl)ethoxy)-1,5-naphthyridineAusbeute 54 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A 25 mL round bottom flask at rt was charged with (R)-3-fluoropyrrolidine hydrochloride (124 mg, 0.99 mmol). To this was added potassium carbonate (365 mg, 2.64 mmol), 3-(2-bromoethoxy)-8-chloro-1,5-naphthyridine (190 mg, 0.66 mmol), sodium iodide (149 mg, 0.99 mmol) and DMF (2 mL). Reaction mixture placed in oil bath preheated to 60° C. and allowed to stir for 16 hrs. Reaction mixture passed through celite cake, rinsed with 10% MeOH/DCM and filtrate concentrated to afford yellow oil. This was purified by ISCO silica gel chromatography (20-40% EtOAC/Hexanes) to afford (R)-8-chloro-3-(2-(3-fluoropyrrolidin-1-yl)ethoxy)-1,5-naphthyridine (105 mg, 54% yield). MS [M+H]=296.2. Calc'd for C14H5ClFN3O=295.7. The following compounds were prepared in a similar fashion as 8-chloro-3-(2-(3-fluoropyrrolidin-1-yl)ethoxy)-1,5-naphthyridine:

Aufarbeitung

  1. customReaction mixture
  2. customplaced in oil bath
  3. custompreheated to 60° C.
  4. customReaction mixture
  5. washrinsed with 10% MeOH/DCM and filtrate
  6. concentrationconcentrated
  7. customto afford yellow oil
  8. customThis was purified by ISCO silica gel chromatography (20-40% EtOAC/Hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-d58b8b1611a54b79ace0ba71d6fa298a
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08198448B2

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