反応 #9589

反応方程式

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

収率 64.1%

溶媒

water

反応条件

後処理

1. 1
   その他the flask was flushed with nitrogen
2. 2
   workup.ADDITIONPalladium(II) acetate (0.0013 g) in toluene (0.200 mL) was added
3. 3
   その他the flask was again flushed with nitrogen
4. 4
   その他The flask was sealed
5. 5
   温度to cool to room temperature
6. 6
   workup.ADDITIONthe mixture was diluted with dichloromethane and water
7. 7
   その他The layers were separated
8. 8
   抽出the aqueous fraction was extracted with dichloromethane
9. 9
   洗浄washed sequentially with water and saturated aqueous sodium chloride
10. 10
    乾燥dried over sodium sulfate
11. 11
    ろ過filtered
12. 12
    濃縮concentrated under reduced pressure
13. 13
    その他Purification of the residue by flash column chromatography
14. 14
    洗浄eluting with a gradient of CMA/chloroform and subsequent recrystallization from acetonitrile

実験手順

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.

出典