Diisopropylethylamine → 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

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.

1. concentrationthe mixture was concentrated in vacuo
2. additionthe residue was diluted with ethyl acetate (10 mL)
3. washwashed with 1 M aqueous hydrochloric acid solution (2×5 mL) and with brine
4. dry with materialdried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. additionThe residue was diluted with dichloromethane
8. filtrationfiltered
9. concentrationThe filtrate was concentrated under reduced pressure onto silica
10. custompurified by silica gel chromatography (Gradient: 0% to 100% ethyl acetate in heptane)

ORDレコード

ord-bb11c556c7cc4b6096b969c847d84d21

出典データセット

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09138486B2