1132940-88-5Relevant articles and documents
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 0051; 0054; 0055, (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.
COMPOUNDS AS HEPATITIS C VIRUS (HCV) INHIBITORS AND USES THEREOF IN MEDICINE
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Paragraph 00200, (2016/01/25)
Provided herein are compounds of Formula (I), or a stereoisomer, a geometric isomer, an enantiomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, which are used in the treatment of HCV
A scalable route to an unusual 3,3-dimethyl-2,3-dihydrobenzofuran ring system present in an HCV drug candidate
Wang, Ping,Briggs, Andrew J.
, p. 656 - 661 (2014/06/09)
A scalable synthesis of a key intermediate used for the preparation of an HCV inhibitor containing an unusual dimethyldihydrobenzofuran ring is described. A key element for the successful completion of the synthesis was the correct ordering of a sequence of bromination, chlorination, and methylation to provide optimized selectivity and improved yield. A tin hydride-mediated ring closure was replaced with a more environmentally benign sulfuric acid-catalyzed Friedel-Crafts reaction. The overall yield for the preparation of the key intermediate was increased from less than 5 to 40%.
ANT1VIRAL COMPOUNDS AND USES THEREOF
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Page/Page column 74, (2010/11/05)
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 178, (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.
ANTI-INFECTIVE PYRIMIDINES AND USES THEREOF
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Page/Page column 107, (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.
