Method for synthesizing cladribine through nitration-chlorination method

• Main Authors: CHEN GAIRONG, XIA RAN, SUN LIPING
• Format: Patent
• Language: Chinese; English
• Published: 02.03.2016
• Subjects: CHEMISTRY; CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION ORPROCESSING OF GOODS; DERIVATIVES THEREOF; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; METALLURGY; NUCLEIC ACIDS; NUCLEOSIDES; NUCLEOTIDES; ORGANIC CHEMISTRY; SUGARS; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS; TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINSTCLIMATE CHANGE

The invention discloses a novel method for synthesizing cladribine through a nitration-chlorination method. According to the method, cheap 6-chloropurine and 1-chloro-2,3,5-tris-O-p-chlorobenzoyl-D-ribose are taken as raw materials, sodium hydride is taken as alkali, acetonitrile is taken as reaction solvent, and a beta isomer is obtained through a high-selectivity reaction; the obtained beta isomer does not need to remove protecting groups, the beta isomer reacts with trifluoromethanesulfonic anhydride after being separated, and nitryl is introduced at the second position; the nitryl is transformed into chlorine atoms in an ethanol solution of NH4Cl; two steps of reactions of protecting group removal and chlorine atom ammonolysis are completed in a methanol solution saturated by ammonia gas, and then the cladribine is obtained through four steps at the total yield of 78%. The method has the advantages that the raw materials are low in cost and easy to obtain, the technology is simple and convenient, the tota