Diisopropylethylamine → Benzyl [2-[({4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]pyridin-3-yl}amino)carbonyl]-7-(4-methyl-3-oxopiperazin-1-yl)quinolin-3-yl]carbamate

To a mixture of 3-{[(benzyloxy)carbonyl]amino}-7-(4-methyl-3-oxopiperazin-1-yl)quinoline-2-carboxylic acid (0.012 g, 0.028 mmol), tert-butyl ((3R,4R,5S)-1-(3-aminopyridin-4-yl)-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methylpiperidin-3-yl)carbamate (0.019 g, 0.043 mmol) and HATU (0.034 g, 0.089 mmol) in DMF (0.30 mL) was added DIPEA (0.019 mL, 0.11 mmol). The mixture was stirred at room temperature for 2 h. The mixture was diluted with 5 mL of EtOAc and 3 mL of 1 M NaOH. The resulting layers were separated and the aqueous layer was extracted with EtOAc. The organic layers were combined and concentrated under reduced pressure. To the resulting residue, 1 mL of 4 M HCl in dioxane and 1 mL of MeOH were added. The mixture was stirred at room temperature for 1 h, then concentrated under reduced pressure. The resulting residue was purified by preparative HPLC (XBridge™ C18 column, eluting with a gradient of MeCN/water containing 0.1% NH4OH, at a flow rate of 60 mL/min.) to afford the sub-title compound (0.007 g, 40%). LCMS calc. for C34H39N8O5 [M+H]+: m/z=639.3. found: 639.3.

1. customThe resulting layers were separated
2. extractionthe aqueous layer was extracted with EtOAc
3. concentrationconcentrated under reduced pressure
4. additionTo the resulting residue, 1 mL of 4 M HCl in dioxane and 1 mL of MeOH were added
5. stirringThe mixture was stirred at room temperature for 1 h
6. concentrationconcentrated under reduced pressure
7. customThe resulting residue was purified by preparative HPLC (XBridge™ C18 column
8. washeluting with a gradient of MeCN/water containing 0.1% NH4OH, at a flow rate of 60 mL/min.)

ORDレコード

ord-4244cb9c1c1e4e85907a711d6eb9af34

出典データセット

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09278950B2