تفاعل #9589

معادلة التفاعل

tert-Butyl[4-(4-amino-7-bromo-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-ylmethyl)benzyl]carbamate

pyridine-3-boronic acid 1,3-propanediol cyclic ester

sodium carbonate

n-propanol

→

tert-butyl{4-[4-amino-2-ethoxymethyl-7-(pyridin-3-yl)-1H-imidazo[4,5-c]quinolin-1-ylmethyl]benzyl}carbamate

المردود 64.1%

المذيبات

water

ظروف التفاعل

المعالجة

1. 1
   أخرىthe flask was flushed with nitrogen
2. 2
   workup.ADDITIONPalladium(II) acetate (0.0013 g) in toluene (0.200 mL) was added
3. 3
   أخرىthe flask was again flushed with nitrogen
4. 4
   أخرىThe flask was sealed
5. 5
   درجة الحرارةto cool to room temperature
6. 6
   workup.ADDITIONthe mixture was diluted with dichloromethane and water
7. 7
   أخرىThe layers were separated
8. 8
   استخلاصthe aqueous fraction was extracted with dichloromethane
9. 9
   غسيلwashed sequentially with water and saturated aqueous sodium chloride
10. 10
    تجفيفdried over sodium sulfate
11. 11
    ترشيحfiltered
12. 12
    تركيزconcentrated under reduced pressure
13. 13
    أخرىPurification of the residue by flash column chromatography
14. 14
    غسيلeluting with a gradient of CMA/chloroform and subsequent recrystallization from acetonitrile

الإجراء التجريبي

tert-Butyl[4-(4-amino-7-bromo-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-ylmethyl)benzyl]carbamate (1.15 g, 2.1 mmol), triphenylphosphine (0.005 g), pyridine-3-boronic acid 1,3-propanediol cyclic ester (0.365 g, 2.2 mmol), and n-propanol (3.67 mL) were combined. Aqueous sodium carbonate (2M, 1.12 mL) and water (0.6 mL) were added to the mixture and the flask was flushed with nitrogen. Palladium(II) acetate (0.0013 g) in toluene (0.200 mL) was added, and the flask was again flushed with nitrogen. The flask was sealed and heated in an oil bath at a temperature of 105° C. for 16 hours. The reaction was allowed to cool to room temperature and the mixture was diluted with dichloromethane and water. The layers were separated and the aqueous fraction was extracted with dichloromethane. The organic fractions were combined, washed sequentially with water and saturated aqueous sodium chloride, dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification of the residue by flash column chromatography eluting with a gradient of CMA/chloroform and subsequent recrystallization from acetonitrile yielded 0.725 g of tert-butyl{4-[4-amino-2-ethoxymethyl-7-(pyridin-3-yl)-1H-imidazo[4,5-c]quinolin-1-ylmethyl]benzyl}carbamate as flocculent white crystals, m.p. 195.5–197.0° C.

المصدر