Sodium Carbonate → 5'-Chloro-2'-fluoro-6-(3-fluorobenzylamino)-2,4'-bipyridine-5-carbonitrile

HRID 1963881

Reaktionsgleichung

Reaktionsgleichung von HRID 1963881
Cl[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=2)[N:3]=1.[Cl:19][C:20]1[C:21](B(O)O)=[CH:22][C:23]([F:26])=[N:24][CH:25]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[Cl:19][C:20]1[C:21]([C:2]2[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([NH:10][CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=3)[N:3]=2)=[CH:22][C:23]([F:26])=[N:24][CH:25]=1

Komponenten

6

Edukt 3

HCID 10340Sodium CarbonateHCID 44754822(5-Chloro-2-fluoropyridin-4-yl)boronic acidHCID 86650611HCID 86650611, Verbindung

Produkt 1

HCID 669371535'-Chloro-2'-fluoro-6-(3-fluorobenzylamino)-2,4'-bipyridine-5-carbonitrileAusbeute 33 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418807HCID 178418807, VerbindungKatalysatorHCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

6-chloro-2-(3-fluorobenzylamino)nicotinonitrile (0.602 g, 2.30 mmol), 5-chloro-2-fluoropyridin-4-ylboronic acid (1.21 g, 6.91 mmol), and sodium carbonate (2.99 mL, 5.99 mmol, 2M in H2O) were dissolved in DME (10.5 mL). The resulting solution was then degassed by sparging with argon for 5 min. It was then treated with PdCl2(dppf) CH2Cl2 adduct (0.376 g, 0.460 mmol). The resulting reaction mixture was heated in the microwave at 120° C. for 10 min. It was then filtered through a pad of Celite. The filtrate was concentrated in vacuo. The resulting residue was subjected to silica gel column chromatography. Elution using 5 EtOAc/95 hexanes to 50 EtOAc/50 hexanes yielded 0.2689 g (33%) of 5′-chloro-2′-fluoro-6-(3-fluorobenzylamino)-2,4′-bipyridine-5-carbonitrile. LCMS (m/z): 357.2 (MH+), retention time=1.02 min.

Aufarbeitung

  1. customThe resulting solution was then degassed
  2. customby sparging with argon for 5 min
  3. customThe resulting reaction mixture
  4. filtrationIt was then filtered through a pad of Celite
  5. concentrationThe filtrate was concentrated in vacuo
  6. washElution

Quellen und Nachweise

ORD-Eintrag
ord-cc9f1fe7b1e342d399118193725b94cb
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08415381B2

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