反応 #161928

反応方程式

#24

(2R,3R)-3-methoxy-2-methyl-N-(2-phenylethyl)-3-[(2S)-pyrrolidin-2-yl]propanamide, hydrochloride salt

#32

N-[(9H-fluoren-9-ylmethoxy)carbonyl]-2-methylalanyl-N-[(2R,3S,4S)-1-carboxy-2-methoxy-4-methylhexan-3-yl]-N-methyl-L-valinamide

diisopropylethylamine

HATU

→

#55

収率 19.5%

N-[(9H-fluoren-9-ylmethoxy)carbonyl]-2-methylalanyl-N-{(3R,4S,5S)-3-methoxy-1-[(2S)-2-{(1R,2R)-1-methoxy-2-methyl-3-oxo-3-[(2-phenylethyl)amino]propyl}pyrrolidin-1-yl]-5-methyl-1-oxoheptan-4-yl}-N-methyl-L-valinamide

収率 19.5%

溶媒

dichloromethane

反応条件

後処理

1. 1
   濃縮the mixture was concentrated in vacuo
2. 2
   workup.ADDITIONthe residue was diluted with ethyl acetate (10 mL)
3. 3
   洗浄washed with 1 M aqueous hydrochloric acid solution (2×5 mL) and with brine
4. 4
   乾燥dried over sodium sulfate
5. 5
   ろ過filtered
6. 6
   濃縮concentrated in vacuo
7. 7
   workup.ADDITIONThe residue was diluted with dichloromethane
8. 8
   ろ過filtered
9. 9
   濃縮The filtrate was concentrated under reduced pressure onto silica
10. 10
    その他purified by silica gel chromatography (Gradient: 0% to 100% ethyl acetate in heptane)

実験手順

To a solution of #24 (104 mg, 0.256 mmol, 1 eq.) in dichloromethane (10 mL, 0.094 M) were added #32 (156 mg, 0.256 mmol, 0.9 eq.), diisopropylethylamine (135 μL, 0.768 mmol, 3 eq.) and HATU (120 mg, 0.307 mmol, 1.2 eq.). After stirring for 18 hours, the mixture was concentrated in vacuo and the residue was diluted with ethyl acetate (10 mL), washed with 1 M aqueous hydrochloric acid solution (2×5 mL) and with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was diluted with dichloromethane and filtered. The filtrate was concentrated under reduced pressure onto silica and purified by silica gel chromatography (Gradient: 0% to 100% ethyl acetate in heptane) to give #55 (44 mg, 19%) as a white solid. LC-MS: m/z 884.5 [M+2H+], retention time=1.04 minutes.

出典