Potassium Carbonate → 4'-Fluoro-7'-(2-fluoropyridin-3-yl)-2'-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-5-amine

HRID 455640Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 455640
Br[C:2]1[CH:15]=[C:14]2[C:5]([O:6][C:7]3[C:8]([F:24])=[CH:9][C:10]([O:22][CH3:23])=[CH:11][C:12]=3[C:13]32[N:20]=[C:19]([NH2:21])[CH2:18][O:17][CH2:16]3)=[CH:4][CH:3]=1.[F:25][C:26]1[C:31](B(O)O)=[CH:30][CH:29]=[CH:28][N:27]=1.C(=O)([O-])[O-].[K+].[K+]>CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl.O1CCOCC1>[F:24][C:8]1[C:7]2[O:6][C:5]3[C:14](=[CH:15][C:2]([C:31]4[C:26]([F:25])=[N:27][CH:28]=[CH:29][CH:30]=4)=[CH:3][CH:4]=3)[C:13]3([N:20]=[C:19]([NH2:21])[CH2:18][O:17][CH2:16]3)[C:12]=2[CH:11]=[C:10]([O:22][CH3:23])[CH:9]=1

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 27832702-Fluoropyridine-3-boronic acidHCID 584659217'-Bromo-4'-fluoro-2'-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-5-amine

Produkt 1

HCID 674375114'-Fluoro-7'-(2-fluoropyridin-3-yl)-2'-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-5-amineAusbeute 74,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)KatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

A 250 ml RBF was charged with 7′-bromo-4′-fluoro-2′-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (2.73 g, 6.94 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (0.492 g, 0.694 mmol) and 2-fluoropyridin-3-ylboronic acid (1.467 g, 10.41 mmol). Dioxane (40 mL) and potassium carbonate (1M in water; 20.83 mL, 20.83 mmol) were added and the mixture was flushed with argon and heated at 85° C. for 30 minutes. The mixture was cooled to RT, diluted with EtOAc and the organic layer was separated and concentrated in vacuo to give a yellow residue. After triturating with 10 ml of ethanol the solid was filtered off, washed with EtOH (2×1 ml) and dried on air overnight to afford 4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (2.11 g, 5.15 mmol).

Aufarbeitung

  1. customthe mixture was flushed with argon
  2. temperatureThe mixture was cooled to RT
  3. additiondiluted with EtOAc
  4. customthe organic layer was separated
  5. concentrationconcentrated in vacuo
  6. customto give a yellow residue
  7. customAfter triturating with 10 ml of ethanol the solid
  8. filtrationwas filtered off
  9. washwashed with EtOH (2×1 ml)
  10. customdried on air overnight

Quellen und Nachweise

ORD-Eintrag
ord-615b58780a4c450fafb18687b9c316c7
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08497264B2

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