反应详情

To a solution of (3-thienylsulphonyl)acetonitrile (59.4 mg, 0.318 mmol) in DMF (1 mL) was added NaH (95%, 8.08 mg, 0.344 mmol). After stirring 5 min at room temperature, 5-isothiocyanato-2-methylbenzofuran (50 mg, 0.265 mmol) was added in one portion. The reaction was heated at 50° C. for 30 min. To the mixture was added 1-[[(3S)-3-aminohexahydro-2-oxo-1H-azepin-1-yl]acetyl]pyrrolidine (76.0 mg, 0.318 =mol), WSC (101.7 mg, 0.53 mmol) and N,N-dimethyl 4-pyridinamine (cat.) in that order. The reaction mixture was stirred at room temperature overnight. Water was added to the reaction and the mixture was extracted with ethyl acetate three times. The combined organic fractions were washed once with brine, dried over magnesium sulfate and evaporated. The residue was chromatographed (silica, 5% methanol/ethyl acetate) to provide 1-[[(3S)-3-[[2-[(3-thienyl)sulfonyl]-2-cyano-1-[(2-methyl-5-benzofuranyl)amino]-1-ethenyl]amino]hexahydro-2-oxo-1H-azepin-1-yl]acetyl]pyrrolidine (63.0 mg, 41%): HPLC (method A) tR 3.65 min; LRMS (ESI, pos. ion spectrum) m/z 582 (M+H).

1. temperatureThe reaction was heated at 50° C. for 30 min
2. stirringThe reaction mixture was stirred at room temperature overnight
3. extractionthe mixture was extracted with ethyl acetate three times
4. washThe combined organic fractions were washed once with brine
5. dry with materialdried over magnesium sulfate
6. customevaporated
7. customThe residue was chromatographed (silica, 5% methanol/ethyl acetate)