- Synthesis of filibuvir. Part III. Development of a process for the reductive coupling of an aldehyde and a β-keto-lactone
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Development of a reductive coupling of a β-keto-lactone and an aldehyde is described, in which the Hantzsch ester serves as an inexpensive and convenient reducing agent. Structural features in the β-keto-lactone rendered standard reductive coupling conditions ineffective, requiring development of a specific addition and temperature protocol. Identification of one of the reactants as Ames positive required a single-digit parts per million control strategy for this impurity in the final active pharmaceutical ingredient (API).
- Ide, Nathan D.,Ragan, John. A.,Bellavance, Gabriel,Brenek, Steve J.,Cordi, Eric M.,Jensen, Grace O.,Jones, Kris N.,France, Danny La,Leeman, Kyle R.,Letendre, Leo J.,Place, David,Stanchina, Corey L.,Sluggett, Gregory W.,Strohmeyer, Holly,Blunt, Jon,Meldrum, Kevin,Taylor, Stuart,Byrne, Ciaran,Lynch, Denis,Mullane, Sandra,O'Sullivan, Maria M.,Whelan, Marcella
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- INHIBITORS OF HEPATITIS C VIRUS POLYMERASE
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The present invention provides, among other things, compounds represented by the general Formula (I) and pharmaceutically acceptable salts thereof, wherein X, Y, R1A, R1B, R2, and R3 are as defined in classes and subclasses herein and compositions (e.g., pharmaceutical compositions) comprising such compounds, which compounds are useful as inhibitors of hepatitis C virus polymerase, and thus are useful, for example, as medicaments for the treatment of HCV infection.
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Page/Page column 102-103
(2012/06/30)
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- METHODS FOR THE PREPARATION OF HCV POLYMERASE INHIBITORS
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The present invention relates to methods and compounds useful in the preparation of compounds of the formula (I).
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Page/Page column 55-56
(2008/06/13)
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- Development of a synthetic process towards a hepatitis C polymerase inhibitor
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The synthesis of 2-(4-{2-[(2R)-2-Cyclopentyl-5-(5,7-dimethyl-[1,2,4] triazolo[1,5-a]pyrimidin-2-ylmethyl)-4-hydroxy-6-oxo-3,6-dihydro-2H-pyran-2-yl] -ethyl}-2-fluoro-phenyl)-2-methyl-propionitrile (1) on multikilogram scale is described. Initial synthesis
- Camp, David,Matthews, Chris F.,Neville, Sean T.,Rouns, Michael,Scott, Robert W.,Truong, Yen
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p. 814 - 821
(2012/12/22)
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- INHIBITORS OF HEPATITIS C VIRUS RNA-DEPENDENT RNA POLYMERASE, AND COMPOSITIONS AND TREATMENTS USING THE SAME
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The present invention provides compounds of formula (4), and their pharmaceutically acceptable salts and solvates, which are useful as inhibitors of the Hepatitis C virus (HCV) polymerase enzyme and are also useful for the treatment of HCV infections in HCV-infected mammals. The present invention also provides pharmaceutical compositions comprising compounds of formula (4), their pharmaceutically acceptable salts and solvates. Furthermore, the present invention provides intermediate compounds and methods useful in the preparation of compounds of formula (4).
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Page/Page column 104
(2008/06/13)
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- Inhibitors of hepatitis C virus RNA-dependent RNA polymerase, and compositions and treatments using the same
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The invention relates to compounds of the formula 1 and to pharmaceutically acceptable salts, solvates, prodrugs and metabolites thereof, wherein W, Z, R1 and R2, are as defined herein. The invention also relates to methods of treating Hepatitis C virus in mammals by administering the compounds of formula 1, and to pharmaceutical compositions for treating such disorders, which contain the compounds of formula 1. The invention also relates to methods of preparing the compounds of formula 1.
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Page/Page column 158
(2008/06/13)
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- INHIBITORS OF HEPATITIS C VIRUS RNA-DEPENDENT RNA POLYMERASE, AND COMPOSITIONS AND TREATMENTS USING THE SAME
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The invention relates to compounds of the formula (I) and to pharmaceutically acceptable salts, solvates, prodrugs and metabolites thereof, wherein W, Z, R1and R2, are as defined herein. The invention also relates to methods of treating Hepatitis C virus in mammals by administering the compounds of formula (I), and to pharmaceutical compositions for treating such disorders, which contain the compounds of formula (I). The invention also relates to methods of preparing the compounds of formula (I).
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