Synthesis of RP 48497, an impurity of eszopiclone.
RP 48497 is a photodegradation product of eszopiclone, a non-benzodiazepine sedative-hypnotic used in the treatment of insomnia. We report herein the first synthesis of RP 48497 via reduction, chlorination, and recyclization of 6-(5-chloropyridin-2-yl)-7-hydroxy-6,7-dihydropyrrolo[3,4-b]pyrazin-5-one (3), a key intermediate in the synthesis of eszopiclone. The structure of RP 48497 was confirmed by its (1)H-NMR and MS data. The mechanism of the reduction step in the synthesis of RP 48497 was also studied and the key parameters were determined. These findings should be important for quality control purposes in the manufacture of eszopiclone.
Sha
Yu
Y
Key Lab of New Drug Design and Discovery of Liaoning Province, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, P. R. China. mscheng@syphu.edu.cn.
Zhang
Lei
L
Du
Gui-Jie
GJ
Ren
Jian
J
Cheng
Mao-Sheng
MS
D053961:Azabicyclo Compounds / Q000737:chemistry*; D002713:Chlorine; D003500:Cyclization; D000069582:Eszopiclone; D006993:Hypnotics and Sedatives / Q000138:chemical synthesis*; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry*; D011719:Pyrazines / Q000737:chemistry; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy
D053961:Azabicyclo Compounds; D006993:Hypnotics and Sedatives; D010879:Piperazines; D011719:Pyrazines; C533383:RP 48497; D002713:Chlorine; D000069582:Eszopiclone