تفاعل #168416

معادلة التفاعل

6-chloro-4-(5-chloropyridin-3-yl)-2-[1-(3-fluoropyridin-2-yl)ethyl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine

DMF

→

4-(5-chloropyridin-3-yl)-2-[1-(3-fluoropyridin-2-yl)ethyl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile

ظروف التفاعل

المعالجة

1. 1
   أخرىthe reaction was deoxygenated
2. 2
   أخرىby purging with nitrogen for 10 minutes
3. 3
   workup.ADDITION1,1′-Bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (65.5 mg, 0.08 mmol) was added
4. 4
   أخرىthe reaction mixture was again deoxygenated for 5 minutes
5. 5
   درجة الحرارةThe reaction was then cooled to room temperature
6. 6
   workup.ADDITIONdiluted with water (25 mL)
7. 7
   استخلاصextracted with ethyl acetate (2×25 mL)
8. 8
   غسيلThe combined organic extracts were washed with water (1×25 mL) and brine (1×25 mL)
9. 9
   تجفيفdried over anhydrous Na2SO4
10. 10
    ترشيحfiltered
11. 11
    تركيزconcentrated
12. 12
    أخرىThe residue was purified by silica gel chromatography (eluting with 35% EtOAc/petroleum ether)

الإجراء التجريبي

To a stirred solution of 6-chloro-4-(5-chloropyridin-3-yl)-2-[1-(3-fluoropyridin-2-yl)ethyl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine (400 mg, 0.80 mmol) in DMF (16 mL) was added zinc cyanide (37.7 mg, 0.32 mmol), and the reaction was deoxygenated by purging with nitrogen for 10 minutes. 1,1′-Bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (65.5 mg, 0.08 mmol) was added, and the reaction mixture was again deoxygenated for 5 minutes. The reaction was heated to 140° C. for 5 h under a nitrogen atmosphere. The reaction was then cooled to room temperature, diluted with water (25 mL), and extracted with ethyl acetate (2×25 mL). The combined organic extracts were washed with water (1×25 mL) and brine (1×25 mL), dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified by silica gel chromatography (eluting with 35% EtOAc/petroleum ether) to yield 4-(5-chloropyridin-3-yl)-2-[1-(3-fluoropyridin-2-yl)ethyl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ES/APCl calcd. for C27H26ClFN6 [M+H]+ 489. found 489.

المصدر