反应详情

To lithium 4-{[1-(3,4-dichlorobenzyl)-4-piperidinyl]amino}-5-oxobutanoate (Example 351, step ii) (0.292 g) in dichloromethane (6 ml) was added N,N-dimethylformamide (1.5 ml), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.183 g), 1-hydroxybenzotriazole hydrate (0.130 g), N′-hydroxy-2-pyrazinecarboximidamide (0.110 g) and triethylamine (0.161 g). The reaction mixture was left to stir for 24 hours before removal of dichloromethane under reduced pressure. Pyridine (5 ml) was added and heated at reflux for 5 hours. Pyridine was removed under reduced pressure followed by the addition of water. The solution was extracted three times with dichloromethane. The pooled organic phase was washed once with water, once with saturated brine and dried over magnesium sulfate. After filtration the product was azeotroped twice with toluene and was purified by RPHPLC (75%-5%, 0.1% ammonium acetate/acetonitrile). Solvent was removed under reduced pressure to give the title compound (0.067 g).

1. waitThe reaction mixture was left
2. temperatureheated
3. temperatureat reflux for 5 hours
4. customPyridine was removed under reduced pressure
5. additionfollowed by the addition of water
6. extractionThe solution was extracted three times with dichloromethane
7. washThe pooled organic phase was washed once with water, once with saturated brine
8. dry with materialdried over magnesium sulfate
9. filtrationAfter filtration the product
10. customwas azeotroped twice with toluene
11. customwas purified by RPHPLC (75%-5%, 0.1% ammonium acetate/acetonitrile)
12. customSolvent was removed under reduced pressure