Réaction #358363

Équation de réaction

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

Rendement 77.0%

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

Rendement 77.0%

Solvants

ethyl acetate

tetrahydrofuran

Conditions de réaction

Traitement

1. 1
   AutreThe reaction mixture was equipped with a cold water condenser
2. 2
   workup.ADDITIONwas added
3. 3
   TempératureThe mixture was heated to 60° C. for 45 min
4. 4
   TempératureThe reaction was cooled to room temperature
5. 5
   Autretransferred to a separatory funnel
6. 6
   Lavagewas washed with a saturated aqueous sodium chloride solution (2×250 mL)
7. 7
   AutreThe organic layer was separated
8. 8
   Séchagedried 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
    AutreThe resulting mixture was purified by flash chromatography (Biotage 75L)
13. 13
    Lavageeluted with 15%-30% ethyl acetate in hexanes
14. 14
    AutreThe desired fractions were collected
15. 15
    Concentrationconcentrated under vacuum
16. 16
    Autreto afford a solid which
17. 17
    Autrewas dried under high vacuum

Mode opératoire

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 75L) 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