Reaktion #313191

Reaktionsgleichung

8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine

2-bromo-5-fluoro-3-methylbenzo[b]thiophene

triphenylphosphine

Cs2CO3

→

title compound

Ausbeute 65.0%

8-(1-Ethyl-propyl)-2,6-dimethyl-3-(5-fluoro-3-methyl-benzo[b]thiophen-2-yl)-imidazo[1,2-b]pyridazine

Ausbeute 65.0%

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigedegassed
2. 2
   Sonstigeby sparging with nitrogen for 30 min.
3. 3
   TemperaturThe reaction is cooled
4. 4
   Sonstigepartitioned between MTBE (10 mL)
5. 5
   WaschenThe organic phase is washed with satd
6. 6
   TrocknenNH4Cl solution (2×5 mL), dried (Na2SO4)
7. 7
   Einengenconcentrated in vacuo to a brown film, which
8. 8
   Sonstigechromatographed (10 g of silica gel; heptane to 5% EtOAc in heptane to 10% EtOAc in heptane) and fractions
9. 9
   workup.ADDITIONcontaining pure product
10. 10
    Einengenconcentrated
11. 11
    workup.STIRRINGThe residue is stirred in warm heptane (6 mL) for 10 min.
12. 12
    SonstigeLight yellow crystals are separated
13. 13
    Waschenwashed with cold heptane
14. 14
    Sonstigedried
15. 15
    SonstigeThe product is recrystallized from MeOH (3 mL)

Vorschrift

A mixture of 8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (435 mg, 2.0 mmol, 1.0 equiv), 2-bromo-5-fluoro-3-methylbenzo[b]thiophene (564 mg, 2.3 mmol, 1.15 equiv), triphenylphosphine (100 mg, 0.38 mmol, 0.19 equiv), Cs2CO3 (1.37 g, 4.2 mmol, 2.1 equiv) and Pd2 dba3 (88 mg, 0.096 mmol, 0.048 equiv) in DMF (4.5 mL, degassed by sparging with nitrogen for 30 min. prior to use) is heated at 130° C. for 4 hr (magnetically-stirred under an atmosphere of N2). The reaction is cooled and partitioned between MTBE (10 mL) and satd. NH4Cl solution (10 mL). The organic phase is washed with satd. NH4Cl solution (2×5 mL), dried (Na2SO4) and concentrated in vacuo to a brown film, which is adsorbed onto silica gel (1.0 g). Material is flash chromatographed (10 g of silica gel; heptane to 5% EtOAc in heptane to 10% EtOAc in heptane) and fractions containing pure product were combined and concentrated. The residue is stirred in warm heptane (6 mL) for 10 min. then refrigerated at −20° C. for 24 hr. Light yellow crystals are separated, washed with cold heptane and dried. The product is recrystallized from MeOH (3 mL) to provide the title compound as light yellow crystals (453 mg, 65%).

Quelle