Dimethylformamide → 5-bromo-N-[4-chloro-5-({7-cyano-2-[(cyclopropylcarbonyl)amino]-1,3-benzothiazol-6-yl}oxy)-2-fluorophenyl]-1-methyl-1H-pyrazole-4-carboxamide

To a solution of 5-bromo-1-methyl-1H-pyrazole-4-carboxylic acid (68 mg, 0.331 mmol) in tetrahydrofuran (1 mL) were added oxalyl chloride (35 μL, 0.408 mmol) and N,N-dimethylformamide (5 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 (1 mL). N-[6-(5-Amino-2-chloro-4-fluorophenoxy)-7-cyano-1,3-benzothiazol-2-yl]cyclopropanecarboxamide (90 mg, 0.223 mmol) produced in Example 23(vi) was added to the solution, and the mixture was stirred at room temperature for 1 hr. The reaction mixture was diluted with ethyl acetate (15 mL), washed successively with 5% aqueous sodium hydrogen carbonate solution (7 mL) and saturated brine (7 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 silica gel column chromatography (ethyl acetate/n-hexane=60/40→100/0), and the obtained solution was concentrated under reduced pressure. The residue was crystallized from ethyl acetate to give the title compound (34 mg, 26%) as a white powder.

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. dissolutionthe residue was dissolved in N,N-dimethylacetamide (1 mL)
3. stirringthe mixture was stirred at room temperature for 1 hr
4. washwashed successively with 5% aqueous sodium hydrogen carbonate solution (7 mL) and saturated brine (7 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 silica gel column chromatography (ethyl acetate/n-hexane=60/40→100/0)
9. concentrationthe obtained solution was concentrated under reduced pressure
10. customThe residue was crystallized from ethyl acetate

ORD 기록

ord-300aa824581d4f81a398787f40aa5f1c

출처 데이터셋

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08497274B2