Ethyl 3-(3-chloro-2,4,5-trifluorophenyl)-3-oxopropanoate → Ethyl 1-[4-(t-butylamino)-5-fluoropyrimidin-2-yl]-8-chloro-6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate

温度

90 °C

To 3 ml of chloroform solution of ethyl 3-ethoxy-2-(3-chloro-2,4,5-trifluorobenzoyl)acrylate prepared from 210 mg of ethyl 3-chloro-2,4,5-trifluorobenzoylacetate by normal process was added 340 mg of 2-amino-4-(t-butylamino)-5-fluoropyrimidine. The solution was concentrated under reduced pressure. To the residue were added 550 mg of anhydrous potassium carbonate and 2 ml of N,N-dimethylformamide, and the mixture was stirred at 90° C. for 1 hour and 10 minutes and allowed to cool. The solution was separated by adding 30 ml of chloroform and 300 ml of distilled water, and the chloroform layer was washed twice with 300 ml of distilled water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (silica gel, 16 g; eluent: chloroform:methanol, 200:1), and the corresponding fractions were collected and concentrated under reduced pressure. To the residue was added 0.5 ml of ethanol, and the precipitate was collected by filtration and washed with ethanol and diisopropylether successively to obtain 98 mg of the title compound as a colorless powder.

1. concentrationThe solution was concentrated under reduced pressure
2. additionTo the residue were added 550 mg of anhydrous potassium carbonate and 2 ml of N,N-dimethylformamide
3. temperatureto cool
4. customThe solution was separated
5. additionby adding 30 ml of chloroform and 300 ml of distilled water
6. washthe chloroform layer was washed twice with 300 ml of distilled water
7. dry with materialdried over anhydrous magnesium sulfate
8. concentrationconcentrated under reduced pressure
9. customThe residue was separated by column chromatography (silica gel, 16 g; eluent: chloroform:methanol, 200:1)
10. customthe corresponding fractions were collected
11. concentrationconcentrated under reduced pressure
12. additionTo the residue was added 0.5 ml of ethanol
13. filtrationthe precipitate was collected by filtration
14. washwashed with ethanol and diisopropylether successively

ORDレコード

ord-5a5d5a07919c46ad96b37bd32688de47

出典データセット

uspto-grants-1999_12

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US05998436