反応 #2286310

反応方程式

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

収率 77.0%

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

収率 77.0%

溶媒

ethyl acetate

tetrahydrofuran

反応条件

後処理

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

実験手順

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

出典