تفاعل #2286310

معادلة التفاعل

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

المردود 77.0%

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

المردود 77.0%

المذيبات

ethyl acetate

tetrahydrofuran

ظروف التفاعل

المعالجة

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

الإجراء التجريبي

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

المصدر