Triethylamine → 3-(1-cyano-1-methylethyl)-N-[3-({2-[(cyclopropylcarbonyl)amino]-7-(hydroxymethyl)-1,3-benzothiazol-6-yl}oxy)phenyl]benzamide

Temperatur

4 °C

To a solution of methyl 6-[3-({[3-(1-cyano-1-methylethyl)phenyl]carbonyl}amino)phenoxy]-2-[(cyclopropylcarbonyl)amino]-1,3-benzothiazole-7-carboxylate (200 mg, 0.369 mmol) produced in Example 46(iv) in tetrahydrofuran (8 mL) were added triethylamine (101 μL, 0.738 mmol) and isobutyl chloroformate (96 μL, 0.738 mmol) at 4° C., and the mixture was stirred at 4° C. for 30 min. Insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was dissolved in tetrahydrofuran (2 mL), sodium borohydride (42 mg, 1.10 mmol) and methanol (2 mL) were added, 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 (20 mL), washed successively with 1N hydrochloric acid (5 mL), 5% aqueous sodium hydrogen carbonate solution (10 ml) and saturated brine (5 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=20/80→60/40), and the obtained solution was concentrated under reduced pressure to give the title compound (108 mg, 55%) as a pale-yellow powder.

1. filtrationInsoluble material was filtered off
2. concentrationthe filtrate was concentrated under reduced pressure
3. dissolutionThe obtained residue was dissolved in tetrahydrofuran (2 mL)
4. stirringthe mixture was stirred at room temperature for 2 hr
5. concentrationThe reaction mixture was concentrated under reduced pressure
6. additionThe obtained residue was diluted with ethyl acetate (20 mL)
7. washwashed successively with 1N hydrochloric acid (5 mL), 5% aqueous sodium hydrogen carbonate solution (10 ml) and saturated brine (5 mL)
8. dry with materialdried over anhydrous sodium sulfate
9. filtrationInsoluble material was filtered off
10. concentrationthe filtrate was concentrated under reduced pressure
11. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate/n-hexane=20/80→60/40)
12. concentrationthe obtained solution was concentrated under reduced pressure

ORD-Eintrag

ord-b78c93eba8f844a2920983bdc95ddcef

Quelldatensatz

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08143258B2