1132935-63-7Relevant academic research and scientific papers
Discovery and Development of Metal-Catalyzed Coupling Reactions in the Synthesis of Dasabuvir, an HCV-Polymerase Inhibitor
Barnes, David M.,Shekhar, Shashank,Dunn, Travis B.,Barkalow, Jufang H.,Chan, Vincent S.,Franczyk, Thaddeus S.,Haight, Anthony R.,Hengeveld, John E.,Kolaczkowski, Lawrence,Kotecki, Brian J.,Liang, Guangxin,Marek, James C.,McLaughlin, Maureen A.,Montavon, Donna K.,Napier, James J.
, p. 4873 - 4892 (2019/02/05)
Dasabuvir (1) is an HCV polymerase inhibitor which has been developed as a part of a three-component direct-acting antiviral combination therapy. During the course of the development of the synthetic route, two novel coupling reactions were developed. First, the copper-catalyzed coupling of uracil with aryl iodides, employing picolinamide 16 as the ligand, was discovered. Later, the palladium-catalyzed sulfonamidation of aryl nonaflate 33 was developed, promoted by electron-rich palladium complexes, including the novel phosphine ligand, VincePhos (50). This made possible a convergent, highly efficient synthesis of dasabuvir that significantly reduced the mutagenic impurity burden of the process.
Preparation method of bulk drug dasabuvir
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Paragraph 0057; 0058; 0059, (2018/01/04)
The invention discloses a preparation method of a bulk drug dasabuvir. The method comprises the following steps: 1, carrying out a deprotection reaction on the amino group of A0 used as a raw material; and 2, amidating the A1 to obtain a dasabuvir intermediate N-(6-4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalene-2-yl)methanesulfonate. The preparation method of the bulk drug dasabuvir, adopting an amino group protection-boronation-amino group deprotection-amino group amidation-substitution-purification synthesis route, has the advantages of simple steps, mild reaction conditions, stable stability of the intermediate, easiness in reaction quenching, easiness in intermediate separation, and facilitation of industrial large-scale production.
PROCESS FOR PREPARING ANTIVIRAL COMPOUNDS
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, (2012/02/01)
This disclosure is directed to: (a) processes for preparing a compound and salts thereof that, inter alia, are useful for inhibiting hepatitis C virus (HCV); (b) intermediates useful for the preparation of the compound and salts; (c) pharmaceutical compositions comprising the compound or salts; and (d) methods of use of such compositions.
ANTI-INFECTIVE PYRIMIDINES AND USES THEREOF
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Page/Page column 107-108, (2009/04/25)
This invention relates to: (a) compounds and salts thereof that, inter alia, inhibit HCV; (b) intermediates useful for the preparation of such compounds and salts; (c) compositions comprising such compounds and salts; (d) methods for preparing such intermediates, compounds, salts, and compositions; (e) methods of use of such compounds, salts, and compositions; and (f) kits comprising such compounds, salts, and compositions.
URACIL OR THYMINE DERIVATIVE FOR TREATING HEPATITIS C
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Page/Page column 180, (2009/04/25)
Present application relates to the compounds of formula I useful to treat hepatitis C (HCV) infections. In the structure of the disclosed compounds is the uracil or thymine derivative linked via a phenylene into either fused 2-ring cyclic system (R6) or alternatively via additional two-atom linker (L) to a 5-6 membered monocycle (R6). Application further discloses polymorphs and pseudopolymorphs of two specific compounds: N-(6(3-t-butyl-5-(2>4-dioxo-3,4-dihydropyrimidin-1 (2H)- y!)2-methoxy-phenyl)naphthalen-2-yl)methanesulfonamide and (E)-N-(4(3-t- butyl-5-(2,4-dioxo-3)4-dihydropyrimidin-1 (2H)-yl)2-methoxy-styryl- phenyl)methanesulfonamide.
