Potassium Phosphate, Tribasic → (S)-7-(2-fluoropyridin-3-yl)-3-methoxy-2',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,3'-[1,4]oxazin]-5'-amine

HRID 455650Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 455650
Br[C:2]1[CH:3]=[C:4]2[C@:15]3([N:20]=[C:19]([NH2:21])[CH2:18][O:17][CH2:16]3)[C:14]3[CH:13]=[C:12]([O:22][CH3:23])[N:11]=[CH:10][C:9]=3[O:8][C:5]2=[CH:6][CH:7]=1.[F:24][C:25]1[C:30](B(O)O)=[CH:29][CH:28]=[CH:27][N:26]=1.P([O-])([O-])([O-])=O.[K+].[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>[F:24][C:25]1[C:30]([C:2]2[CH:3]=[C:4]3[C@:15]4([N:20]=[C:19]([NH2:21])[CH2:18][O:17][CH2:16]4)[C:14]4[CH:13]=[C:12]([O:22][CH3:23])[N:11]=[CH:10][C:9]=4[O:8][C:5]3=[CH:6][CH:7]=2)=[CH:29][CH:28]=[CH:27][N:26]=1

Komponenten

5

Edukt 3

HCID 62657Potassium Phosphate, TribasicHCID 27832702-Fluoropyridine-3-boronic acidHCID 58465867(S)-7-bromo-3-methoxy-2',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,3'-[1,4]oxazin]-5'-amine

Produkt 1

HCID 67440000(S)-7-(2-fluoropyridin-3-yl)-3-methoxy-2',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,3'-[1,4]oxazin]-5'-amineAusbeute 95,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)Katalysator

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A microwave vial was charged with (S)-7-bromo-3-methoxy-2′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazin]-5′-amine (0.065 g, 0.173 mmol), 2-fluoropyridin-3-ylboronic acid (0.049 g, 0.346 mmol), potassium phosphate (0.110 g, 0.518 mmol), and bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (6.12 mg, 8.64 μmol). The vial was flushed with Ar (g), dioxane (0.648 mL) and water (0.216 mL) were added in sequence. The vial was sealed and heated in a Biotage Initiator microwave reactor for 30 min at 100° C. The reaction was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with EtOAc, and the combined organic layers were washed with brine, dried with sodium sulfate, filtered, and concentrated. The material was purified via column chromatography (0-10% MeOH/EtOAc) to afford 65 mg of (S)-7-(2-fluoropyridin-3-yl)-3-methoxy-2′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazin]-5′-amine as a light yellow solid.

Aufarbeitung

  1. customThe vial was flushed with Ar (g), dioxane (0.648 mL) and water (0.216 mL)
  2. additionwere added in sequence
  3. customThe vial was sealed
  4. additionThe reaction was diluted with ethyl acetate
  5. washwashed with water
  6. extractionThe aqueous layer was extracted with EtOAc
  7. washthe combined organic layers were washed with brine
  8. dry with materialdried with sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe material was purified via column chromatography (0-10% MeOH/EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-3bf688708ca644ec842c7ac1778c84e5
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08497264B2

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