Reaction #68663

Reaction equation

5-bromo-3-methylisothiazole

isopropylmagnesium chloride

3,6-dichloropyridazine

3,6-dichloropyridazine

→

desired product

3-chloro-6-(3-methylisothiazol-5-yl)pyridazine

Solvents

THF

THF

THF

Conditions

Workup

1. 1
   Temperaturethe reaction was heated to 50° C. for 16 hours
2. 2
   TemperatureThe reaction was then cooled to 23° C.
3. 3
   Otherquenched with 60 mL of satd
4. 4
   workup.ADDITIONThe mixture was mixed with celite and 100 mL of EtOAc
5. 5
   OtherThe insoluble material was removed by filtration
6. 6
   workup.ADDITIONThe filtrate was diluted with 40 mL of EtOAc and 30 mL of water
7. 7
   OtherThe organic phase was separated
8. 8
   Washwashed with 60 mL of brine
9. 9
   Dryingdried over Na2SO4
10. 10
    Concentrationconcentrated in vacuo
11. 11
    OtherThe residue was purified by a silica gel column chromatography (10% to 80% hex/EtOAc)

Procedure

To a solution of 5-bromo-3-methylisothiazole (2.42 g, 14 mmol) in 20 mL of THF at −45° C. was added isopropylmagnesium chloride (19 ml, 19 mmol) in THF (1 M). After 20 minutes, zinc(II) chloride (41 ml, 20 mmol) in THF (0.5 M) was added and the solution was warmed up to rt. 3,6-dichloropyridazine (2.4 g, 16 mmol), 3,6-dichloropyridazine (2.4 g, 16 mmol) and Q-Phos (2.5 g) were added and the reaction was heated to 50° C. for 16 hours. The reaction was then cooled to 23° C. and quenched with 60 mL of satd. NH4Cl aq. solution. The mixture was mixed with celite and 100 mL of EtOAc. The insoluble material was removed by filtration. The filtrate was diluted with 40 mL of EtOAc and 30 mL of water. The organic phase was separated and washed with 60 mL of brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (10% to 80% hex/EtOAc) to afford red solid as desired product. MS (ESI pos. ion) m/z: 212 (MH+). Calc'd exact mass for C8H6ClN3S: 211.

Source