反应详情

To a stirred solution of (S)-4,4,N1,N1-tetramethyl-pentane-1,2-diamine hydrochloride salt (Intermediate 2, 0.100 g, 0.43 mmol) in methanol (5 mL) at 0° C. was added triethylamine (0.12 g, 0.16 ml, 1.2 mmol). After 10 min of stirring at the same temperature, a solution of 2-(3-formyl-benzyl)-1,1-dioxo-1λ6-isothiazolidine-3-carboxylic acid((1S,2S,3S,5R)-2,6,6-trimethyl-bicyclo[3.1.1]hept-3-yl)-amide (0.181 g, 0.43 mmol) in methanol (1 mL) was added and stirring was continued for an additional 15 min at room temperature. The reaction mixture was again brought into 0° C. and sodium cyanoborohydride (0.022 g, 0.35 mmol) and acetic acid (0.2 mL) were added simultaneously into the reaction mixture. After stirring overnight at room temperature, the reaction mixture was concentrated under reduced pressure, the residue was diluted with ethyl acetate (5 mL), washed with water (3 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to provide crude 2-{3-[((S)-1-dimethylaminomethyl-3,3-dimethyl-butylamino)methyl]-benzyl}-1,1-dioxo-1λ6-isothiazolidine-3-carboxylic acid((1S,2S,3S,5R)-2,6,6-trimethyl-bicyclo[3.1.1]hept-3-yl)-amide (0.216 g, 89%).

1. stirringstirring
2. waitwas continued for an additional 15 min at room temperature
3. customwas again brought into 0° C.
4. stirringAfter stirring overnight at room temperature
5. concentrationthe reaction mixture was concentrated under reduced pressure
6. additionthe residue was diluted with ethyl acetate (5 mL)
7. washwashed with water (3 mL)
8. dry with materialdried over anhydrous sodium sulfate
9. concentrationconcentrated under reduced pressure