Hydrochloric Acid → (S)-6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-1-(1-hydroxypropan-2-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

온도

100 °C

To a solution of (S)-ethyl 6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-1-(1-hydroxypropan-2-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate (Example 97, 200 mg, 0.34 mmol, 1 equiv.) in tetrahydrofuran (1 mL) and methanol (1 mL) was added 2 M lithium hydroxide (0.339 mL). The mixture was stirred in the microwave at 100° C. for 15 min The reaction mixture was cooled to room temperature and diluted with water. 1 N HCl was added until pH 3-4 was reached. The reaction mixture was partitioned between ethyl acetate (5 mL) and water (5 mL). The aqueous layer was extracted with ethyl acetate (2×5 mL), and the organics were washed with brine (10 mL), dried over sodium sulfate, and concentrated under reduced pressure. Purification via reverse phase HPLC (C18 column, acetonitrile/water 0-95% gradient) and concentrated under reduced pressure to provide (S)-6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-1-(1-hydroxypropan-2-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid as a light yellow solid (92 mg, 48%).

1. temperaturewas cooled to room temperature
2. customThe reaction mixture was partitioned between ethyl acetate (5 mL) and water (5 mL)
3. extractionThe aqueous layer was extracted with ethyl acetate (2×5 mL)
4. washthe organics were washed with brine (10 mL)
5. dry with materialdried over sodium sulfate
6. concentrationconcentrated under reduced pressure
7. customPurification via reverse phase HPLC (C18 column, acetonitrile/water 0-95% gradient)
8. concentrationconcentrated under reduced pressure

ORD 기록

ord-54fc8814aea2487f9c2aef7c769bac18

출처 데이터셋

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08283361B2