Reaktion #306445

Reaktionsgleichung

6-(1-(6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethyl)quinoline

5-bromo-3-methylisothiazole

CH3CN dry ice

→

6-(1-(6-(3-methylisothiazol-5-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethyl)quinoline

Lösungsmittel

THF

N,N-dimethyl acetamide

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe mixture was then warmed up to rt
2. 2
   workup.STIRRINGto stir for additional 30 minutes
3. 3
   TemperaturThe reaction was warmed up to 50° C. for 6 hours
4. 4
   Sonstigewas quenched with 50 mL of satd
5. 5
   ExtraktionThe mixture was extracted with 150 mL of EtOAc
6. 6
   Waschenthe organic phase was washed with 60 mL of brine
7. 7
   ExtraktionThe aqueous phases were further extracted with 100 mL EtOAc
8. 8
   TrocknenThe combined organics were dried over Na2SO4
9. 9
   Einengenconcentrated in vacuo
10. 10
    SonstigeThe residue was purified by a silica gel column chromatography (EtOAc to 15% MeOH in EtOAc)
11. 11
    Sonstigeto give
12. 12
    Sonstigeafford a red solid

Vorschrift

To a solution of 5-bromo-3-methylisothiazole (1.00 g, 5.6 mmol) in 10 mL of THF at −45° C. (CH3CN/dry ice) was added isopropylmagnesium chloride LiCl complex (7.9 ml, 7.9 mmol) (LiCl complex, 1 M in THF). The mixture was stirred at −45° C. for 20 minutes and to this was added zinc chloride, 0.5 M in THF (17 ml, 8.4 mmol) slowly via a syringe. The mixture was then warmed up to rt and continued to stir for additional 30 minutes. 6-(1-(6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethyl)quinoline (0.5787 g, 1.9 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.51 g, 0.56 mmol) and Q-Phos (0.65 g) in 15 mL of N,N-dimethyl acetamide was added to the reaction mixture. The reaction was warmed up to 50° C. for 6 hours and was quenched with 50 mL of satd. NH4Cl aq. solution. The mixture was extracted with 150 mL of EtOAc and the organic phase was washed with 60 mL of brine. The aqueous phases were further extracted with 100 mL EtOAc. The combined organics were dried over Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (EtOAc to 15% MeOH in EtOAc) to give afford a red solid. MS (ESI pos. ion) m/z: 373 (MH+). Calc'd exact mass for C20H16N6S: 372.

Quelle