Reaktion #2286310

Reaktionsgleichung

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

Ausbeute 77.0%

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

Ausbeute 77.0%

Lösungsmittel

ethyl acetate

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

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

Vorschrift

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

Quelle