반응 #2286310

반응 방정식

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

수율 77.0%

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

수율 77.0%

용매

ethyl acetate

tetrahydrofuran

반응 조건

후처리

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

실험 절차

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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