518048-02-7Relevant articles and documents
(Chloromethyl)dimethylchlorosilane-KF: A Two-Step Solution to the Selectivity Problem in the Methylation of a Pyrimidone Intermediate en Route to Raltegravir
Stathakis, Christos I.,Gkizis, Petros L.,Alexandraki, Elli S.,Trakossas, Sakellarios,Terzidis, Michael,Neokosmidis, Efstratios,Zacharis, Constantinos K.,Vasiliadou, Christina,Vastardi, Elli,Andreou, Thanos,Zitrou, Asteria,Varvogli, Anastasia-Aikaterini,Koftis, Theocharis V.
, p. 1413 - 1418 (2017)
The present work describes a two-step process, namely, silylation with (chloromethyl)dimethylchlorosilane and desilylation, to address the selectivity problem in the N-methylation of a pyrimidone intermediate toward the synthesis of the raltegravir active pharmaceutical ingredient. The said methodology delivers the desired drug substance in which the O-methylated impurity content is below the detection limit by high-performance liquid chromatography analysis. Moreover, this two-step, one-pot procedure provides an apparent advantage in terms of environmental impact with respect to the optimum approach described in the literature, while it compares equally well in terms of cost and operational simplicity.
PROCESS FOR PREPARING COMPOUNDS USEFUL AS INTERMEDIATES FOR THE PREPARATION OF RALTEGRAVIR
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Page/Page column 23-24, (2018/04/11)
The invention discloses a novel and selective methylation process used in the preparation of Raltegravir and intermediates. Further disclosed is an improved method for the reaction of intermediate amine compound of formula IIb with oxadiazole intermediate compound of formula V.
Identification, synthesis, and strategy for minimization of potential impurities observed in raltegravir potassium drug substance
Patil, Gulabrao D.,Kshirsagar, Siddheshwar W.,Shinde, Shivnath B.,Patil, Pankaj S.,Deshpande, Mangesh S.,Chaudhari, Ashok T.,Sonawane, Swapnil P.,Maikap, Golak C.,Gurjar, Mukund K.
, p. 1422 - 1429 (2012/10/29)
Multiple sources of anticipated degradation and process impurities of raltegravir potassium drug substance observed during the laboratory optimization and later during its bulk synthesis are described in this article. The impurities were monitored by UPLC, and their structures are tentatively assigned on the basis of fragmentation patterns in LC-MS and NMR spectroscopy. Most of the impurities are synthesized, and their assigned constitutions were confirmed by co-injection in UPLC. In addition to the formation, synthesis, and characterization, strategy for minimizing these impurities to the level accepted by ICH is also described. We feel that our study will be helpful to the generic industry for obtaining chemically pure raltegravir potassium.
