Triethylamine → HCID 67490985, compound

Temperature

70 °C

To a solution of 6-tert-butoxycarbonyl amino-8-azatricyclo[4.3.0.01,3]nonane (290 mg, 1.22 mmol) in dimethyl sulfoxide (2.42 ml) were added triethylamine (0.507 ml, 3.63 mmol) and 7-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-8-methyl-4-oxoquinoline-3-carboxylic acid (337 mg, 1.21 mmol) and the mixture was stirred at 70° C. for 13 days under nitrogen atmosphere. The reaction solution was diluted with ethyl acetate and washed with 10% aqueous solution of citric acid (50 ml), water (60 ml), and saturated aqueous solution of sodium chloride (60 ml). The organic layer was dried with anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform-methanol; 100:0→99:1→98:2→95:5) to afford a pale yellow solid. The solid was dissolved in concentrated hydrochloric acid (1.0 ml) in an ice bath and the aqueous solution was washed with chloroform (30 ml×5). To the aqueous layer was added saturated aqueous solution of sodium hydroxide to adjust pH to 12.0 and the basic aqueous solution was adjusted with hydrochloric acid to pH 7.4. The solution was extracted with chloroform (80 ml×4) and 10% methanol-chloroform (80 ml×1, 50 ml×1). The organic layer was dried with anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by recrystallization from ethanol to afford the title compound 138 mg (29%) as a pale yellow solid.

1. washwashed with 10% aqueous solution of citric acid (50 ml), water (60 ml), and saturated aqueous solution of sodium chloride (60 ml)
2. dry with materialThe organic layer was dried with anhydrous sodium sulfate
3. concentrationconcentrated under reduced pressure
4. customThe residue was purified by silica gel column chromatography (chloroform-methanol; 100:0→99:1→98:2→95:5)
5. customto afford a pale yellow solid
6. washthe aqueous solution was washed with chloroform (30 ml×5)
7. additionTo the aqueous layer was added saturated aqueous solution of sodium hydroxide
8. extractionThe solution was extracted with chloroform (80 ml×4) and 10% methanol-chloroform (80 ml×1, 50 ml×1)
9. dry with materialThe organic layer was dried with anhydrous sodium sulfate
10. concentrationconcentrated under reduced pressure
11. customThe residue was purified by recrystallization from ethanol

ORD record

ord-15b3e1e291ef43b29757c187a37bcca7

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08618094B2