反应详情

To a solution of 0.3 g of Boc-L-Asp(H)-OBn (WO 96/40679) dissolved in 2 mL methanol was added 176 mg of 1-amino-7-(aminomethyl)isoquinoline. After stirring for 30 minutes, a solution of 80 mg sodium cyanoborohydride and 90 mg zinc chloride in 2 mL methanol was added. The mixture was stirred for an additional two hours. After this time, 7 mL of an aqueous 0.2 N sodium hydroxide solution was added and the resulting mixture was concentrated. The residue was treated with 100 mL dichloromethane and 10 mL water, filtered and an additional 100 mL water was added to the filtrate. The organic layer was separated and washed with aqueous 5% sodium hydrogencarbonate and brine. All aqueous layers were washed twice with dichloromethane. The combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel eluting with a gradient of ethyl acetate/dichloromethane/methanol=10/10/1 to dichloromethane/methanol=10/1 to give 146 mg of the title compound.

1. stirringThe mixture was stirred for an additional two hours
2. concentrationthe resulting mixture was concentrated
3. additionThe residue was treated with 100 mL dichloromethane and 10 mL water
4. filtrationfiltered
5. additionan additional 100 mL water was added to the filtrate
6. customThe organic layer was separated
7. washwashed with aqueous 5% sodium hydrogencarbonate and brine
8. washAll aqueous layers were washed twice with dichloromethane
9. dry with materialThe combined organic layers were dried over sodium sulfate
10. concentrationconcentrated
11. customThe residue was purified by column chromatography on silica gel eluting with a gradient of ethyl acetate/dichloromethane/methanol=10/10/1 to dichloromethane/methanol=10/1