Реакция #2286310

Уравнение реакции

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

Выход 77.0%

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

Выход 77.0%

Растворители

ethyl acetate

tetrahydrofuran

Условия реакции

Обработка

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

Методика

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

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