반응 #161928

반응 방정식

#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

수율 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

수율 19.5%

용매

dichloromethane

반응 조건

후처리

1. 1
   농축the mixture was concentrated in vacuo
2. 2
   workup.ADDITIONthe residue was diluted with ethyl acetate (10 mL)
3. 3
   세척washed with 1 M aqueous hydrochloric acid solution (2×5 mL) and with brine
4. 4
   건조dried over sodium sulfate
5. 5
   여과filtered
6. 6
   농축concentrated in vacuo
7. 7
   workup.ADDITIONThe residue was diluted with dichloromethane
8. 8
   여과filtered
9. 9
   농축The filtrate was concentrated under reduced pressure onto silica
10. 10
    기타purified by silica gel chromatography (Gradient: 0% to 100% ethyl acetate in heptane)

실험 절차

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.

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