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US 2014/0275570 A1Published application
Synthesis of an antiviral compound
AssigneeGilead Sciences, Inc.
InventorsJared Wayne Evans, Shinji Fujimori, Grace M. Huynh, Qi Liu, Martin Gerald Teresk
Life of this patent
Estimating the term…
Abstract
The present disclosure provides processes for the preparation of a compound of Formula I: which is useful as an antiviral agent. The disclosure also provides compounds that are synthetic intermediates to compounds of formula.
Claims20
-32. (canceled)
A process for the preparation of a compound of Formula I:
- named 5-(3,3-dimethylbutyn-1-yl)-3-[(cis-4-hydroxy-4-{[(3S)-tetrahydro furan-3-yloxy]methyl}cyclohexyl){[(1R)-4-methylcyclohex-3-en-1-yl]carbonyl}amino]thiophene-2-carboxylic acid, or a stereoisomer, mixture of stereoisomers, pharmaceutically acceptable salt or ester thereof, comprising:
- contacting a compound of Formula IV, named 5-(3,3-dimethylbutyn-1-yl)-3-[(cis-4-hydroxy-4-{[(3S)-tetrahydrofuran-3-yloxy]methyl}cyclohexyl) {[(1R)-4-methylcyclohex-3-en-1-yl]carbonyl}amino]thiophene, or a stereoisomer, mixture of stereoisomers, or salt thereof, with a base in the presence of CO2:
- under carboxylation reaction conditions comprising about a three-fold equivalent of the base and a temperature from about −20° C. to about 20° C., to provide the compound of Formula I or a stereoisomer, mixture of stereoisomers, pharmaceutically acceptable salt or ester thereof.
A process for the preparation of a compound of Formula IV:
- named 5-(3,3-dimethylbutyn-1-yl)-3-[(cis-4-hydroxy-4-{[(3S)-tetrahydrofuran-3-yloxy]methyl}cyclohexyl){[(1R)-4-methylcyclohex-3-en-1-yl]carbonyl}amino]thiophene, or a stereoisomer, mixture of stereoisomers, or salt thereof,
- comprising contacting a compound of Formula III, named 5-(3,3-dimethylbutyn-1-yl)-3-[(cis-4-hydroxy-4-{[(3S)-tetrahydrofuran-3-yloxy]methyl}cyclohexyl)amino]thiophene, or a stereoisomer, mixture of stereoisomers, or salt thereof, with a compound of Formula XI or a stereoisomer, or mixture of stereoisomers thereof:
- wherein:
- X1 is halogen,
- under acylation reaction conditions comprising a base, to provide the compound of Formula IV or a stereoisomer, mixture of stereoisomers, or salt thereof.
2 more elements
A process for the preparation of a compound of Formula III:
- named 5-(3,3-dimethylbutyn-1-yl)-3-[(cis-4-hydroxy-4-{[(3S)-tetrahydrofuran-3-yloxy]methyl}cyclohexyl)amino]thiophene, or a stereoisomer, mixture of stereoisomers, or salt thereof,
- comprising contacting a compound of Formula II, named (cis-4-hydroxy-4-{[(3S)-tetrahydrofuran-3-yloxy]methyl}cyclohexyl)amine, or a stereoisomer, mixture of stereoisomers, or salt thereof, with a compound of Formula X:
- wherein:
- X2 is halogen,
- under N-arylation reaction conditions comprising a catalyst, a ligand, a base, and a phase transfer catalyst, to provide the compound of Formula III or a stereoisomer, mixture of stereoisomers, or salt thereof.
2 more elements
A process for the preparation of a compound of Formula I:
- or a stereoisomer, mixture of stereoisomers, pharmaceutically acceptable salt or ester or thereof, comprising the steps of:
- a) contacting a compound of Formula II, named (cis-4-hydroxy-4-{[(3S)-tetrahydrofuran-3-yloxy]methyl}cyclohexyl)amine, or a stereoisomer, mixture of stereoisomers, or salt thereof, with a compound of Formula X:
- wherein:
- X2 is halogen, under N-arylation reaction conditions comprising a catalyst, a ligand, a base, and a phase transfer catalyst, to provide the compound of Formula III, named 5-(3,3-dimethylbutyn-1-yl)-3-[(cis-4-hydroxy-4-{[(3S)-tetrahydrofuran-3-yloxy]methyl}cyclohexyl)amino]thiophene, or a stereoisomer, mixture of stereoisomers, or salt thereof;
- b) contacting a compound of Formula III or a stereoisomer, mixture of stereoisomers, or salt thereof, with a compound of Formula XI or a stereoisomer, or mixture of stereoisomers thereof:
- wherein:
- X1 is halogen,
- under acylation reaction conditions comprising a base, to provide the compound of Formula IV, named 5-(3,3-dimethylbutyn-1-yl)-3-[(cis-4-hydroxy-4-{[(3S)-tetrahydrofuran-3-yloxy]methyl}cyclohexyl){[(1R)-4-methylcyclohex-3-en-1-yl]carbonyl}amino]thiophene, or a stereoisomer, mixture of stereoisomers, or salt thereof;
- c) contacting a compound of Formula IV or a stereoisomer, mixture of stereoisomers, or salt thereof, with a base in the presence of CO2 under carboxylation reaction conditions comprising about a three-fold equivalent of the base and a temperature from about −20° C. to about 20° C., to provide the compound of Formula I or a stereoisomer, mixture of stereoisomers, pharmaceutically acceptable salt or ester thereof.
6 more elements
Dependencies are inferred from the claim text.