Cyclopropanecarbonyl chloride → Methyl 6-[3-({[3-(1-cyano-1-methylethyl)phenyl]carbonyl}amino)phenoxy]-2-[(cyclopropylcarbonyl)amino]-1,3-benzothiazole-7-carboxylate

To a solution of methyl 2-amino-6-[3-({[3-(1-cyano-1-methylethyl)phenyl]carbonyl}amino)phenoxy]-1,3-benzothiazole-7-carboxylate (0.92 g, 1.88 mmol) in pyridine (5 mL) was added cyclopropanecarbonyl chloride (371 μL, 4.1 mmol), and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated under reduced pressure. The obtained residue was diluted with ethyl acetate (100 mL), washed successively with water (100 mL) and saturated brine (100 mL), and dried over anhydrous sodium sulfate. Insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was suspended in methanol (10 mL), sodium carbonate (250 mg) was added, and the mixture was stirred at room temperature for 4 hr. The reaction mixture was diluted with ethyl acetate (100 mL), washed successively with water (100 mL) and saturated brine (100 mL), and dried over anhydrous sodium sulfate. Insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was successively purified by basic silica gel column chromatography (ethyl acetate/n-hexane=40/60→100/0) and silica gel column chromatography (ethyl acetate/n-hexane=40/60→60/40), and the obtained solution was concentrated under reduced pressure. The residue was crystallized from ethyl acetate/n-hexane to give the title compound (706 mg, 68%) as a pale-yellow powder.

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. additionThe obtained residue was diluted with ethyl acetate (100 mL)
3. washwashed successively with water (100 mL) and saturated brine (100 mL)
4. dry with materialdried over anhydrous sodium sulfate
5. filtrationInsoluble material was filtered off
6. concentrationthe filtrate was concentrated under reduced pressure
7. additionsodium carbonate (250 mg) was added
8. stirringthe mixture was stirred at room temperature for 4 hr
9. additionThe reaction mixture was diluted with ethyl acetate (100 mL)
10. washwashed successively with water (100 mL) and saturated brine (100 mL)
11. dry with materialdried over anhydrous sodium sulfate
12. filtrationInsoluble material was filtered off
13. concentrationthe filtrate was concentrated under reduced pressure
14. customThe obtained residue was successively purified by basic silica gel column chromatography (ethyl acetate/n-hexane=40/60→100/0) and silica gel column chromatography (ethyl acetate/n-hexane=40/60→60/40)
15. concentrationthe obtained solution was concentrated under reduced pressure
16. customThe residue was crystallized from ethyl acetate/n-hexane

ORD record

ord-fd1e523f7bfe43a798ade65939326054

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08497274B2