Reaktion #306314
ord-93b255c8d8a847ad88d25e6f4fb20e47
Reaktionsgleichung
Edukte
Lösungsmittel
Reaktionsbedingungen
Aufarbeitung
- 1TemperaturThe mixture was then warmed up to rt
- 2workup.STIRRINGto stir for additional 30 minutes
- 3TemperaturThe reaction was warmed up to 50° C. for 6 h
- 4Sonstigewas quenched with 50 mL of satd
- 5ExtraktionThe mixture was extracted with 150 mL of EtOAc
- 6Waschenthe organic phase was washed with 60 mL of brine
- 7ExtraktionThe aqueous phases were extracted with 100 mL EtOAc again
- 8TrocknenThe combined organic phases were dried over Na2SO4
- 9Einengenconcentrated in vacuo
- 10SonstigeThe residue was purified by a silica gel column chromatography (EtOAc to 15% MeOH in EtOAc)
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, 1M in THF). The mixture was stirred at −45° C. for 20 minutes and was added zinc chloride, 0.5m in the (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 (o) (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 h 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 extracted with 100 mL EtOAc again. The combined organic phases 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 red solid as desired product 6-(1-(6-(3-methylisothiazol-5-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethyl)quinoline. MS (ESI, pos. ion) m/z: 373.2 (M+1).