Hydrogen chloride-ethyl acetate → 6-fluoro-1-(4-methoxybutyl)-N-(2-methylpropyl)-N-[(3S,5R)-5-(morpholin-4-ylcarbonyl)piperidin-3-yl]-1H-benzimidazole-2-carboxamide dihydrochloride

온도

80 °C

tert-Butyl (3S,5R)-3-{[({4-fluoro-2-[(4-methoxybutyl)amino]phenyl}amino)(oxo)acetyl](2-methylpropyl)amino}-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate (294 mg) was dissolved in acetic acid (5 ml), and the mixture was stirred at 80° C. for 3 days. The reaction mixture was cooled to room temperature, 4M hydrogen chloride-ethyl acetate (5 ml) was added to the reaction mixture, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated, and the residue was diluted with aqueous sodium bicarbonate, and extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to basic silica gel column chromatography, and a fraction eluted with ethyl acetate-methanol (85:15) was concentrated under reduced pressure. The residue was dissolved in ethyl acetate, 4M hydrogen chloride-ethyl acetate (1 ml) was added, and the mixture was concentrated again to give the object product (113 mg).

1. temperatureThe reaction mixture was cooled to room temperature
2. stirringthe mixture was stirred at room temperature for 2 hr
3. concentrationThe reaction mixture was concentrated
4. additionthe residue was diluted with aqueous sodium bicarbonate
5. extractionextracted with ethyl acetate
6. washThe extract was washed with saturated brine
7. dry with materialdried over anhydrous sodium sulfate
8. customThe solvent was evaporated under reduced pressure
9. washa fraction eluted with ethyl acetate-methanol (85:15)
10. concentrationwas concentrated under reduced pressure
11. dissolutionThe residue was dissolved in ethyl acetate
12. addition4M hydrogen chloride-ethyl acetate (1 ml) was added
13. concentrationthe mixture was concentrated again

ORD 기록

ord-bee3b0857baf46ff99161f32b8c30ff5

출처 데이터셋

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08466282B2