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

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence