518048-05-0Relevant articles and documents
Seeking for Selectivity and Efficiency: New Approaches in the Synthesis of Raltegravir
Caputo, Francesco,Corbetta, Stefano,Piccolo, Oreste,Vigo, Daniele
, p. 1149 - 1156 (2020/07/25)
The present work describes the development of an improved synthesis of active pharmaceutical ingredient raltegravir. The isolation of a new process intermediate and the newly developed conditions solve the issue of selectivity typical of this production process, with no need for the use of protecting groups, making the present route more efficient and sustainable than what was reported before. Efficiency comparisons with the previous processes confirm the result here obtained.
A newfangled synthesis of integrase inhibitor drug substance raltegravir potassium
Rao, S. Venkat,Potluri, Vamsi Krishna,Potluri, Ramesh Babu
, p. 2618 - 2622 (2019/10/02)
Raltegravir sodium synthesis was achieved from its one of the key starting materials with retro synthetic approach, in which without using its critical starting material chemically known as 5-methyl-1,3,4-oxadiazole-2-carbonyl chloride and which is more unstable during the synthesis of raltegravir potassium. Almost all the existed literatures commonly using this starting material in its synthesis even it is having a stability issue and hence to achieve a stable and economically viable synthesis. The current research describes a new route of synthesis by constructing an oxadiazole ring in a retro synthetic manner.
A Facile Synthesis of Raltegravir Potassium—An HIV Integrase Inhibitor
Karumanchi, Kishore,Nangi, Gangadhara Bhima Shankar,Danda, Subba Reddy,Chavakula, Ramadas,Korupolu, Raghu Babu,Bonige, Kishore Babu
, p. 2683 - 2690 (2019/08/21)
A facile, cost-effective, and commercially viable synthesis of Raltegravir Potassium (1) has been developed from 2-(1-amino-1-methyl-ethyl)-N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-4-pyrimidinecarboxamide (9) with high purity and in good yields. In addition, a new approach for the synthesis of key amine intermediate (9) of Raltegravir Potassium (1) from commercially available 2-amino-2-methylpropanenitrile hydrochloride (2) is also described. The key features of the synthesis are fewer synthetic steps, employing the inexpensive reagents and eco-friendly.
PROCESS FOR THE PREPARATION OF RALTEGRAVIR
-
Page/Page column 23, (2019/06/09)
The present invention refers to a process for the preparation of Raltegravir and pharmaceutically acceptable salts thereof.
Preparation method of pyrimidinone amide type compound
-
Paragraph 0047; 0048; 0049, (2018/10/19)
The invention discloses a pyrimidinone amide type compound and a preparation method thereof. A pyrimidinone compound is taken as a starting material and is subjected to four-step chemical conversion to obtain TN-A005 and an analogue thereof, and an intermediate can be prepared from methyl tetrazole. A one-pot method is used for feeding in the whole preparation process, post-treatment purificationof each step is recrystallization or dispersion washing, the use of means such as silica gel column chromatography is avoided, the preparation technology is greatly simplified, the preparation efficiency is improved, and the total yield can reach 50%. The method is simple and convenient in preparation steps and can improve the preparation efficiency.
(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 (2017/09/22)
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
-
, (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.
AN IMPROVED PROCESS FOR THE PREPARATION OF RALTEGRAVIR
-
, (2016/06/13)
The present invention provides a process for the preparation of crystalline anhydrous compound of Formula (X), Further, the present invention relates to the use of compound of Formula (X) preparation of Raltegravir (I) or its pharmaceutically acceptable salt thereof.
SYNTHESIS OF RALTEGRAVIR
-
, (2015/02/25)
The present invention relates to a novel synthetic route for the preparation of raltegravir and pharmaceutically acceptable salts, starting from 2-amino-2-methylpropanenitrile and oxadiazole carbonyl chloride, through the formation of a pyrimidinone intermediate of formula (V).
Hydroxyl may not be indispensable for raltegravir: Design, synthesis and SAR Studies of raltegravir derivatives as HIV-1 inhibitors
Wang, Ziwen,Wang, Mingxiao,Yao, Xue,Li, Yue,Qiao, Wentao,Geng, Yunqi,Liu, Yuxiu,Wang, Qingmin
, p. 361 - 369 (2012/06/30)
A series of raltegravir derivatives 20-42 were prepared and systematically evaluated for their anti-HIV activity. The bioassay results showed that most of the compounds possess good to excellent anti-HIV activity. Especially, compounds 25 and 35 with subpicomole IC50 values seemed to be the most potent anti-HIV agents among all of the reported synthesized compounds. These compounds may therefore be considered as new potent anti-HIV agents. The 5-hydroxyl modification of raltegravir derivatives significantly increased the anti-HIV activity, which indicates that the hydroxyl may not be indispensable for raltegravir. The introducing of acyl at 5-position of raltegravir derivatives is favorable for antiviral activity. In addition, a high-throughput cell-based assay method with pseudotyped virus stocks was developed and used to identify HIV inhibitors.