Dimethylformamide → (S)-4'-fluoro-7'-(2-fluoro-5-methylpyridin-3-yl)-2'-morpholino-5H-spiro[oxazole-4,9'-xanthen]-2-amine

HRID 335924Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 335924
FC(F)(F)S(O[C:7]1[CH:20]=[C:19]2[C:10]([O:11][C:12]3[C:13]([F:32])=[CH:14][C:15]([N:26]4[CH2:31][CH2:30][O:29][CH2:28][CH2:27]4)=[CH:16][C:17]=3[C@@:18]32[CH2:24][O:23][C:22]([NH2:25])=[N:21]3)=[CH:9][CH:8]=1)(=O)=O.[F:35][C:36]1[C:41](B(O)O)=[CH:40][C:39]([CH3:45])=[CH:38][N:37]=1.CN(C=O)C.C(=O)([O-])[O-].[Na+].[Na+]>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:32][C:13]1[C:12]2[O:11][C:10]3[C:19](=[CH:20][C:7]([C:41]4[C:36]([F:35])=[N:37][CH:38]=[C:39]([CH3:45])[CH:40]=4)=[CH:8][CH:9]=3)[C@@:18]3([CH2:24][O:23][C:22]([NH2:25])=[N:21]3)[C:17]=2[CH:16]=[C:15]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[CH:14]=1

Komponenten

7

Edukt 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 447548582-Fluoro-5-methylpyridine-3-boronic acidHCID 86658488(S)-2-amino-4'-fluoro-2'-morpholino-5H-spiro[oxazole-4,9'-xanthene]-7'-yl trifluoromethanesulfonate

Produkt 1

HCID 58466320(S)-4'-fluoro-7'-(2-fluoro-5-methylpyridin-3-yl)-2'-morpholino-5H-spiro[oxazole-4,9'-xanthen]-2-amine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

A resealable vial was charged with (S)-2-amino-4′-fluoro-2′-morpholino-5H-spiro[oxazole-4,9′-xanthene]-7′-yl trifluoromethanesulfonate (130 mg, 0.258 mmol; prepared as described in Method BB40), tetrakis(triphenylphosphine)palladium(0) (29.8 mg, 0.026 mmol), 2-fluoro-5-methylpyridin-3-ylboronic acid (64.0 mg, 0.413 mmol), DMF (1.3 mL) and 2 M aqueous sodium carbonate (387 μL, 0.775 mmol). The vial was sealed and the mixture stirred for 2 hr at 85° C. The mixture was cooled and diluted with EtOac (6 mL) and water (2 ml). The organic layer was filtered through celite, concentrated, and purified by reverse phase HPLC (Gilson, 15-90% MeCN in 0.1% aq. TFA). The fractions containing product were concentrated in vacuo, neutralized with saturated sodium bicarbonage and extracted with ethyl acetate. Organic layer was washed with brine, and concentrated. The residue was redissoved in ˜1 mL 1:1 MeCN/water and liophilized to afford (S)-4′-fluoro-7′-(2-fluoro-5-methylpyridin-3-yl)-2′-morpholino-5H-spiro[oxazole-4,9′-xanthen]-2-amine.

Aufarbeitung

  1. customThe vial was sealed
  2. temperatureThe mixture was cooled
  3. filtrationThe organic layer was filtered through celite,
  4. concentrationconcentrated
  5. custompurified by reverse phase HPLC (Gilson, 15-90% MeCN in 0.1% aq. TFA)
  6. additionThe fractions containing product
  7. concentrationwere concentrated in vacuo
  8. extractionextracted with ethyl acetate
  9. washOrganic layer was washed with brine
  10. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-debf4caa0dc441ffb118a2d260324f28
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08883782B2

Notizen zur Reaktion

Wird geladen…