Acetonitrile → HCID 71150699, Verbindung

HRID 407258

Reaktionsgleichung

Reaktionsgleichung von HRID 407258
[NH2:1][C:2]1[C:7]([F:8])=[C:6](Cl)[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[C:3]=1[O:14][CH3:15].[CH3:16][O:17][C:18]1[N:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1.[F-].[Cs+].C(#N)C>O1CCOCC1.O.[Cl-].[Na+].O.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]>[NH2:1][C:2]1[C:3]([O:14][CH3:15])=[C:4]([C:10]([O:12][CH3:13])=[O:11])[N:5]=[C:6]([C:21]2[CH:22]=[N:23][C:18]([O:17][CH3:16])=[CH:19][CH:20]=2)[C:7]=1[F:8]

Komponenten

9

Edukt 4

HCID 6342AcetonitrileHCID 25953Cesium fluorideHCID 2734368(6-Methoxypyridin-3-yl)boronic acidHCID 86675409Methyl 4-amino-6-chloro-5-fluoro-3-methoxypicolinate

Produkt 1

HCID 71150699HCID 71150699, VerbindungAusbeute 28,4 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 962WaterLösungsmittel2×HCID 312751,4-DioxaneLösungsmittelHCID 57417360Sodium chloride; waterLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

To a tube, methyl 4-amino-6-chloro-5-fluoro-3-methoxypicolinate (500 mg, 2.131 mmol), (6-methoxypyridin-3-yl)boronic acid (391 mg, 2.56 mmol), [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (78 mg, 0.107 mmol) and Cesium Fluoride (647 mg, 4.26 mmol) were charged as solids. The tube was sealed and charged with inert atmosphere. The solids were then diluted with Dioxane (5700 μl) and Water (1400 μl). The resulting suspension was heated to 85° C. for 18 hrs. The reaction solution was poured in to a brine solution. The aqueous phase was extracted with EtOAc (3×25 mL). The combined organic layers were dried over MgSO4, filtered and concentrated under vacuum. The product was purified (flash chromatography: silica, 5-50% EtOAc in Hex 16 CV; C18 5-100% ACN in H2O 16 CV) to yield methyl 4-amino-3-fluoro-5,6′-dimethoxy-[2,3′-bipyridine]-6-carboxylate (186 mg, 0.605 mmol, 28.4% yield). ESIMS for m/z 308 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 3.77 (s, 3H), 3.86 (s, 3H), 3.92 (s, 3H), 6.53 (s, 2H), 6.95 (dd, J=8.6, 0.8 Hz, 1H), 8.10 (ddd, J=8.6, 2.4, 1.1 Hz, 1H), 8.58 (t, J=2.0 Hz, 1H). 19F NMR (376 MHz, DMSO-d6) δ −141.20.

Aufarbeitung

  1. customThe tube was sealed
  2. additioncharged with inert atmosphere
  3. extractionThe aqueous phase was extracted with EtOAc (3×25 mL)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe product was purified (flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-133516b77e0e46818f6bc5a227386ebe
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08754229B2

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