反应详情

To a suspension of 33.00 g (89.97 mmol) of (+/−)-5-amino-6-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-2,3,6,7-tetrahydro-[1,4]diazepine-1-carboxylic acid ethyl ester hydrochloride (1:1) in 300 mL of tetrahydrofuran was added 6.47 g (161.94 mmol) of sodium hydride (60% in oil), the reaction mixture was stirred at room temperature for 1 h and 17.47 g (89.97 mmol) of ethyl 3-(pyrimidin-4-yl)-3-oxopropionate dissolved in 300 mL of toluene was added. The resulting solution was evaporated to remove tetrahydrofuran, heated under reflux and 5.00 mL of glacial acetic acid was added. The reaction mixture was stirred under reflux for 12 h. The cooled solution was evaporated to remove solvent. The mixture was dissolved in dichloromethane, washed with a saturated aqueous solution of ammonium chloride, saturated aqueous sodium chloride, dried over sodium sulfate and evaporated to dryness. The residue was triturated with diethyl ether and filtered to afford 18.60 g (45%) of the product as a brown powder. The compound was used as such in the next step.

1. additionwas added
2. customThe resulting solution was evaporated
3. customto remove tetrahydrofuran
4. temperatureheated
5. temperatureunder reflux
6. addition5.00 mL of glacial acetic acid was added
7. stirringThe reaction mixture was stirred
8. temperatureunder reflux for 12 h
9. customThe cooled solution was evaporated
10. customto remove solvent
11. dissolutionThe mixture was dissolved in dichloromethane
12. washwashed with a saturated aqueous solution of ammonium chloride, saturated aqueous sodium chloride
13. dry with materialdried over sodium sulfate
14. customevaporated to dryness
15. customThe residue was triturated with diethyl ether
16. filtrationfiltered