反应详情

3-(Pyridin-4-yl)-3,9-diazaspiro[5.5]undecane dihydrochloride (F-09) (0.49 g, 1.62 mmol) was dissolved in DMF and triethylamine (0.45 g, 3.25 mmol), and 2-(tert-butoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-8-carboxylic acid (0.45 g, 1.62 mmol) (available commercially from Ennova, for example) was added, followed by benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (0.93 g, 2.11 mmol) and 4-methylmorpholine (0.53 g, 4.87 mmol). The reaction mixture was stirred for 15 h at RT, and then the solvent was removed in vacuo. The residue was taken up in ethyl acetate and sat. sodium hydrogen carbonate solution, and the phases were separated. The aqueous phase was extracted with ethyl acetate, and the combined organic phases were washed with sat. sodium hydrogen carbonate solution and sat. sodium chloride solution, dried over magnesium sulfate and concentrated in vacuo. The crude product was purified by column chromatography (silica gel, ethyl acetate/methanol 20:1+ammonia solution (25% aq.)). Yield: 0.78 g (98%).

1. customthe solvent was removed in vacuo
2. customsat. sodium hydrogen carbonate solution, and the phases were separated
3. extractionThe aqueous phase was extracted with ethyl acetate
4. washthe combined organic phases were washed with sat. sodium hydrogen carbonate solution and sat. sodium chloride solution
5. dry with materialdried over magnesium sulfate
6. concentrationconcentrated in vacuo
7. customThe crude product was purified by column chromatography (silica gel, ethyl acetate/methanol 20:1+ammonia solution (25% aq.))