1,4-Dioxane → 4-(Benzo[b]thiophen-7-yl)isoquinoline

HRID 593774

Reaktionsgleichung

Reaktionsgleichung von HRID 593774
Br[C:2]1[C:7]2[S:8][CH:9]=[CH:10][C:6]=2[CH:5]=[CH:4][CH:3]=1.[CH:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14](B(O)O)=[CH:13][N:12]=1.O1CCOCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C(Cl)Cl.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].C(Cl)Cl>[S:8]1[CH:9]=[CH:10][C:6]2[CH:5]=[CH:4][CH:3]=[C:2]([C:14]3[C:15]4[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=4)[CH:11]=[N:12][CH:13]=3)[C:7]1=2

Komponenten

7

Edukt 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 3761204Isoquinoline-4-boronic acidHCID 120455387-Bromobenzo[b]thiophene

Produkt 1

HCID 867304304-(Benzo[b]thiophen-7-yl)isoquinolineAusbeute 30 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418807HCID 178418807, VerbindungKatalysatorHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A vessel capable of sealing was charged with a mixture of 7-bromobenzo[b]thiophene (430 mg, 2.018 mmol), isoquinolin-4-ylboronic acid (419 mg, 2.421 mmol), PdCl2(dppf)-CH2Cl2 adduct (82 mg, 0.101 mmol), dioxane (6 mL), and a 2.0 M aqueous solution of K3PO4 (3 mL, 1.41 mmol) and was purged with nitrogen for 10 min. The vessel was sealed and heated at 90° C. for 16 hours. Upon cooling, the reaction mixture was diluted with CH2Cl2 and filtered with CH2Cl2/MeOH washing. The filtrate was concentrated under reduced pressure. The residue was dissolved in CH2Cl2 and washed with water, brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude material was purified by BIOTAGE® eluting with 0%-15% EtOAc/CH2Cl2 at 30 mL/min. Concentration of appropriate fractions provided the title compound (32 mg, 30% yield). LC/MS: Example 109A @ 2.49 min (RT) (Condition G). MS (ES): m/z=262.42 [M+H]+. 1H NMR (400 MHz, CDCl3) δ ppm 9.38 (1 hr, s), 8.71 (1 hr, s), 8.08-8.15 (1 hr, m), 7.96 (1 hr, dd, J=8.06, 1.01 Hz), 7.51-7.71 (4 hr, m), 7.39-7.51 (3 hr, m).

Aufarbeitung

  1. customThe vessel was sealed
  2. temperatureUpon cooling
  3. filtrationfiltered with CH2Cl2/MeOH washing
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. dissolutionThe residue was dissolved in CH2Cl2
  6. washwashed with water, brine
  7. dry with materialdried over anhydrous Na2SO4
  8. concentrationconcentrated under reduced pressure
  9. customThe crude material was purified by BIOTAGE®
  10. washeluting with 0%-15% EtOAc/CH2Cl2 at 30 mL/min

Quellen und Nachweise

ORD-Eintrag
ord-bcd3bf51ef9f45489778d55081e9fe55
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09242967B2

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