反应详情

To lithium 4-{[1-(3,4-dichlorobenzyl)-4-piperidinyl]amino}-4-oxobutanoate (0.292 g) in dichloromethane (6 ml) was added dimethylformamide (1.5 ml), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.183 g), 1-hydroxybenzotriazole hydrate (0.130 g), 4-bromo-N′-hydroxy-1methyl-1H-pyrazole-3-carboximidamide (0.175 g) and triethylamine (0.161 g). Reaction 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 reverse phase hplc (RPHPLC; 75%-5% 0.1% ammonium acetate/acetonitrile). Solvent was removed under reduced pressure to give the title compound (0.164 g).

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