Dimethylformamide → 2-chloro-3-(1-cyanocyclopropyl)-N-[3-({7-cyano-2-[(cyclopropylcarbonyl)amino]-1,3-benzothiazol-6-yl}oxy)phenyl]benzamide

To a solution of 2-chloro-3-(1-cyanocyclopropyl)benzoic acid (75 mg, 0.339 mmol) in tetrahydrofuran (2 mL) were added oxalyl chloride (36 μL, 0.420 mmol) and N,N-dimethylformamide (20 μL), and the mixture was stirred at room temperature for 1 hr. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in N,N-dimethylacetamide (2 mL). N-[6-(3-Aminophenoxy)-7-cyano-1,3-benzothiazol-2-yl]cyclopropanecarboxamide (100 mg, 0.29 mmol) produced in Example 3(vi) was added to the solution, and the mixture was stirred at room temperature for 30 min. The reaction mixture was diluted with ethyl acetate (50 mL), washed successively with 5% aqueous sodium hydrogen carbonate solution (25 mL) and saturated brine (25 mL), and dried over anhydrous sodium sulfate. Insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (ethyl acetate/n-hexane=70/30→100/0), and the obtained solution was concentrated under reduced pressure. The residue was recrystallized from ethyl acetate/n-hexane to give the title compound (113 mg, 72%) as a white powder.

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. dissolutionthe residue was dissolved in N,N-dimethylacetamide (2 mL)
3. stirringthe mixture was stirred at room temperature for 30 min
4. washwashed successively with 5% aqueous sodium hydrogen carbonate solution (25 mL) and saturated brine (25 mL)
5. dry with materialdried over anhydrous sodium sulfate
6. filtrationInsoluble material was filtered off
7. concentrationthe filtrate was concentrated under reduced pressure
8. customThe obtained residue was purified by basic silica gel column chromatography (ethyl acetate/n-hexane=70/30→100/0)
9. concentrationthe obtained solution was concentrated under reduced pressure
10. customThe residue was recrystallized from ethyl acetate/n-hexane

ORD 기록

ord-530469b80ee04e90a45998c11b19c856

출처 데이터셋

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08497274B2