Reaction #2286310

Reaction equation

potassium tert-butoxide

3,6-dichloro-4-isopropyl pyridazine

(4-amino-2,6-dichloro-phenyl)-acetonitrile

→

(4-amino-2,6-dichloro-phenyl)-(6-chloro-5-isopropyl-pyridazin-3-yl)-acetonitrile

Yield 77.0%

(4-Amino-2,6-dichloro-phenyl)-(6-chloro-5-isopropyl-pyridazin-3-yl)-acetonitrile

Yield 77.0%

Solvents

ethyl acetate

tetrahydrofuran

Conditions

Workup

1. 1
   OtherThe reaction mixture was equipped with a cold water condenser
2. 2
   workup.ADDITIONwas added
3. 3
   TemperatureThe mixture was heated to 60° C. for 45 min
4. 4
   TemperatureThe reaction was cooled to room temperature
5. 5
   Othertransferred to a separatory funnel
6. 6
   Washwas washed with a saturated aqueous sodium chloride solution (2×250 mL)
7. 7
   OtherThe organic layer was separated
8. 8
   Dryingdried with magnesium sulfate
9. 9
   Filtrationwas filtered
10. 10
    workup.ADDITIONSilica gel 60 (70-230 mesh) was added to the filtrate
11. 11
    Concentrationthe solvent was concentrated under vacuum
12. 12
    OtherThe resulting mixture was purified by flash chromatography (Biotage 75 L)
13. 13
    Washeluted with 15%-30% ethyl acetate in hexanes
14. 14
    OtherThe desired fractions were collected
15. 15
    Concentrationconcentrated under vacuum
16. 16
    Otherto afford a solid which
17. 17
    Otherwas dried under high vacuum

Procedure

A solution of 3,6-dichloro-4-isopropyl pyridazine (7) (5.54 g, 29.0 mmol) in tetrahydrofuran (116 mL) in a 500 mL round bottom flask (caution: use an extra large flask) was treated with (4-amino-2,6-dichloro-phenyl)-acetonitrile (44) (5.81 g, 28.9 mmol). The reaction mixture was equipped with a cold water condenser and heated to 60° C. The flask was then raised out of the oil bath and potassium tert-butoxide (6.85 g, 57.99 mmol) was added. The mixture was heated to 60° C. for 45 min. The reaction was cooled to room temperature, transferred to a separatory funnel, diluted with ethyl acetate (500 mL) and was washed with a saturated aqueous sodium chloride solution (2×250 mL). The organic layer was separated, dried with magnesium sulfate, and was filtered. Silica gel 60 (70-230 mesh) was added to the filtrate and the solvent was concentrated under vacuum. The resulting mixture was purified by flash chromatography (Biotage 75 L) using silica gel eluted with 15%-30% ethyl acetate in hexanes. The desired fractions were collected and concentrated under vacuum to afford a solid which was dried under high vacuum to afford (4-amino-2,6-dichloro-phenyl)-(6-chloro-5-isopropyl-pyridazin-3-yl)-acetonitrile (45) (7.87 g, 77%) as an orange foam; LRMS for C15H13Cl3N4 (M+H) m/z=355. This compound was used without further purification. Molecular Weight=355.6567; Exact Mass=354.0206

Source