Potassium Carbonate → US8865911, 46a Isomer 2

HRID 539358

Reaktionsgleichung

Reaktionsgleichung von HRID 539358
Br[C:2]1[CH:3]=[C:4]2[C:14](=[CH:15][CH:16]=1)[O:13][C:7]1([CH2:12][CH2:11][CH2:10][O:9][CH2:8]1)[CH2:6][C:5]12[N:20]=[C:19]([NH2:21])[C:18]([CH3:22])=[N:17]1.[Cl:23][C:24]1[CH:25]=[C:26](B(O)O)[CH:27]=[CH:28][CH:29]=1.C([O-])([O-])=O.[K+].[K+]>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].O1CCOCC1>[Cl:23][C:24]1[CH:29]=[C:28]([C:2]2[CH:3]=[C:4]3[C:14](=[CH:15][CH:16]=2)[O:13][C:7]2([CH2:12][CH2:11][CH2:10][O:9][CH2:8]2)[CH2:6][C:5]23[N:20]=[C:19]([NH2:21])[C:18]([CH3:22])=[N:17]2)[CH:27]=[CH:26][CH:25]=1

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 2734323(3-Chlorophenyl)boronic acidHCID 573861526'-Bromo-5-methyl-5'',6''-dihydro-4''H-dispiro[imidazole-2,4'-chromene-2',3''-pyran]-4-amine

Produkt 1

HCID 57386153US8865911, 46a Isomer 2Ausbeute 30,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
130 °C

Versuchsvorschrift

A mixture of 6′-bromo-5-methyl-5″,6″-dihydro-4″H-dispiro[imidazole-2,4′-chromene-2′,3″-pyran]-4-amine (Example 45 Isomer 1, 116 mg, 0.32 mmol), 3-chlorophenylboronic acid (64.7 mg, 0.41 mmol), [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) chloride (26.0 mg, 0.03 mmol), K2CO3 (2 M aq) (0.318 mL, 0.64 mmol) and 1,4-dioxane (2 mL) were added to a microwave vial. The vial was capped, evacuated and filled with argon. The vial was heated in a microwave reactor at 130° C. for 20 min. Brine was added and the residue was extracted with DCM (×3), dried with a phase separator and concentrated under reduced pressure. The crude product was purified by preparative chromatography. The desired fractions were concentrated. Water and DCM were added and the layers separated. The organic phase was dried with a phase separator and concentrated to give isomer 1 of the title compound (38.5 mg, 30% yield) with undetermined configuration: 1 H NMR (500 MHz, DMSO-d6) δ ppm 1.44-1.53 (m, 1 H), 1.83-1.92 (m, 3 H), 2.01 (d, 2 H), 2.22 (s, 3 H), 3.41-3.48 (m, 1 H), 3.56 (d, 1 H), 3.67-3.73 (m, 1 H), 3.99 (d, 1 H), 6.58 (s, 1 H), 6.62 (s, 1 H), 6.95 (d, 1 H), 7.31-7.39 (m, 2 H), 7.39-7.47 (m, 3 H); MS (ES+) m/z 396 [M+H]+.

Aufarbeitung

  1. additionwere added to a microwave vial
  2. customThe vial was capped
  3. customevacuated
  4. additionfilled with argon
  5. additionBrine was added
  6. extractionthe residue was extracted with DCM (×3)
  7. customdried with a phase separator
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was purified by preparative chromatography
  10. concentrationThe desired fractions were concentrated
  11. additionWater and DCM were added
  12. customthe layers separated
  13. customThe organic phase was dried with a phase separator
  14. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-484f3129b6a64e6581ea47086744f3c0
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08865911B2

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