Preparation method of tenofovir alafenamide fumarate impurity

• Main Authors: CHEN XIAOFENG, XIA YUMING, HE LULU, TIAN LEI, HUANG NAN, CAI YULEI, ZHANG WEI, PENG JIEWEI
• Format: Patent
• Language: Chinese; English
• Published: 10.05.2024
• Subjects: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAININGELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN,SULFUR, SELENIUM OR TELLURIUM; CHEMISTRY; METALLURGY; ORGANIC CHEMISTRY

The invention discloses a preparation method of a tenofovir alafenamide fumarate impurity, which comprises the following steps: preparing a compound 1, a compound 2, a compound 3, a compound 4, a compound 5 and a compound 6, specifically, condensing PMPA and HPA to obtain the compound 1; respectively reacting the compound 1 with phenol and L-alanine isopropyl ester under chloro and alkaline conditions to obtain a compound 2 and a compound 3; the preparation method comprises the following steps: condensing PMPA monophenyl ester with L-alanine benzyl ester through chlorination under an alkaline condition, and then reducing and hydrogenating by taking methanol as a solvent to obtain a compound 4; the preparation method comprises the following steps: respectively reacting PMPA monophenyl ester with L-alanine methyl ester and L-alanine ethyl ester through chlorination under an alkaline condition to obtain a compound 5 and a compound 6; the synthesis method disclosed by the invention has the advantages of easily av