反应详情

N-Cyclohexylcarbodiimide, N-methyl polystyrene HL (200-400 mesh) 1.8 mMol/g (650 mg, 1.172 mmol) was suspended in a (1:1) mixture of dichloromethane and dimethylformamide and treated sequentially with benzoic acid (72 mg, 0.58 mmol), 1-hydroxybenzotriazole hydrate (80 mg, 0.58 mmol) and stirred for 10 minutes at room temperature. A solution of 1-[4-(3-piperidin-1-yl-propoxy)-benzyl]-piperazine trihydrochloride (D2) (125 mg, 0.29 mmol) in dichloromethane (1 ml) and triethylamine (0.13 ml, 0.87 mmol) was then added to the reaction and stirred at room temperature for 16 hours. After filtration, the filtrate was applied to a Mega Bond elute SCX ion exchange column washing sequentially with water and methanol, followed by 0.880 ammonia/methanol (1:10) to elute the crude reaction mixture. Purification by silica gel chromatography eluting with a mixture of 0.880 ammonia:methanol:dichloromethane (0.5:4.5:95) to afford the title product (95 mg, 77%); MS (ES+), m/e 422 [M+H]+.

1. stirringstirred at room temperature for 16 hours
2. filtrationAfter filtration
3. washelute SCX ion exchange column
4. washwashing sequentially with water and methanol
5. washto elute the crude
6. customreaction mixture
7. customPurification by silica gel chromatography
8. washeluting with a mixture of 0.880 ammonia:methanol:dichloromethane (0.5:4.5:95)