反应详情

To a stirring suspension of N-Cyclohexylcarbodiimide, N′-methyl polystyrene resin (1.7 mmole/gram, 0.2353 g, 0.4 mmol) in 10 ml of methylene chloride was added the acid 1 (84.3 mg, 0.2 mmol) and HOBT (45.9 mg, 0.34 mmol) which was allowed to stir for 15 minutes at room temperature. Compound 2 (53.75 mg, 0.2 mmol) and DIEA (0.068 ml, 0.4 mmol) were added and the reaction was allowed to stir for 5 hours at room temperature. Then silicycle triamine™ (0.28 g, 1.0 mmol) was added and the reaction was stirred overnight at room temperature. The reaction was filtered and the solvent was removed under reduced pressure. The crude product 3 was used without further purification. Crude compound 3 was dissolved in methylene chloride and Dess-Martin reagent (15% in methylene chloride, 1.13 g, 0.6 mmol) was added and the reaction was allowed to stir at room temperature for 3 hours. The excess Dess-Martin reagent was consumed by adding sodium thiosulfate in saturated sodium bicarbonate. The product was extracted with ethyl acetate and washed with brine. The organic layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure. The product was purified using HPLC to yield 6 mg of final compound 4; LCMS retention time 3:09 minutes, M+1(634.4).

1. stirringto stir for 5 hours at room temperature
2. stirringthe reaction was stirred overnight at room temperature
3. filtrationThe reaction was filtered
4. customthe solvent was removed under reduced pressure
5. customThe crude product 3 was used without further purification
6. dissolutionCrude compound 3 was dissolved in methylene chloride
7. stirringto stir at room temperature for 3 hours
8. customThe excess Dess-Martin reagent was consumed
9. additionby adding sodium thiosulfate in saturated sodium bicarbonate
10. extractionThe product was extracted with ethyl acetate
11. washwashed with brine
12. dry with materialThe organic layer was dried over magnesium sulfate
13. filtrationfiltered
14. concentrationconcentrated under reduced pressure
15. customThe product was purified