Reacción #2286310

Ecuación de reacción

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

Rendimiento 77.0%

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

Rendimiento 77.0%

Disolventes

ethyl acetate

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

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

Procedimiento

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

Fuente