Processes and intermediates for preparing anti-HIV Agents
AssigneeGilead Sciences, Inc.
InventorsRichard Hung Chiu Yu, Brandon Heath Brown, Richard P. Polniaszek, Benjamin R. Graetz, Keiko Sujino, Duong Duc-Phi Tran, Alan Scott Triman, Kenneth M. Kent, Steven Pfeiffer
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Abstract
The invention provides synthetic processes and synthetic intermediates that can be used to prepare compounds having useful anti-HIV properties.
Claims49
A compound selected from the group consisting of:
- wherein;
- Bn is optionally substituted with one or more substituents selected from the group consisting of (C1-C6)alkyl and —O(C1-C6)alkyl;
- R3 is I, R5Se or R5S;
- each R4 is independently (C1-C6)alkyl, (C3-C7)cycloalkyl or aryl, wherein aryl or (C3-C7)cycloalkyl is optionally substituted with one or more (C1-C6)alkyl groups;
- and
- each R5 is independently (C1-C6)alkyl, (C3-C7)cycloalkyl or aryl, wherein aryl or (C3-C7)cycloalkyl is optionally substituted with one or more (C1-C6)alkyl groups;
- or a salt thereof.
A method of preparing a compound of formula 13b:
- or a salt thereof, comprising converting a corresponding compound of formula 12b:
- or a salt thereof, to the compound of formula 13b or the salt thereof, wherein each R4 is independently (C1-C6)alkyl, (C3-C7)cycloalkyl or aryl, wherein any (C3-C7)cycloalkyl or aryl is optionally substituted with one or more (C1-C6)alkyl groups.
A method of preparing a compound of formula 12b:
- or a salt thereof, comprising converting a corresponding compound of formula 11b:
- or a salt thereof, to the compound of formula 12b or the salt thereof, wherein R3 is I, R5Se or R5S and each R4 or R5 is independently (C1-C6)alkyl, (C3-C7)cycloalkyl or aryl, wherein aryl or (C3-C7) cycloalkyl is optionally substituted with one or more (C1-C6)alkyl groups.
A method of preparing a compound of formula 13b:
- or a salt thereof, comprising converting a compound of formula 19b:
- to the compound of formula 13b or the salt thereof.
A method comprising preparing a compound of formula 11b:
- or a salt thereof, comprising converting a compound of formula 19b:
- or a salt thereof, to the compound of formula 11b or the salt thereof, wherein R3 is I, R5Se or R5S and each R4 and R5 is independently (C1-C6)alkyl, (C3-C7)cycloalkyl or aryl, wherein aryl or (C3-C7)cycloalkyl is optionally substituted with one or more (C1-C6)alkyl groups.
A method of preparing a compound of formula 19b:
- comprising converting a compound formula 18b:
- to the compound of formula 19b, wherein Bn is optionally substituted with one or more substituents selected from the group consisting of (C1-C6)alkyl and —O(C1-C6)alkyl.
A compound selected from the group consisting of:
- wherein Bn is optionally substituted with one or more substituents selected from the group consisting of (C1-C6)alkyl and —O(C1-C6)alkyl and W is a leaving group.
A method of preparing a compound of formula 21b:
- comprising reacting compound of formula 20:
- or a salt thereof, with a compound of formula 25b:
- to provide the compound of formula 21b, wherein W is a leaving group.
A method of preparing a compound of formula 25b:
- comprising converting a compound of formula 24b:
- to the compound of formula 25b.
A compound selected from the group consisting of:
- or a salt thereof, wherein Bn is optionally substituted with one or more substituents selected from the group consisting of (C1-C6)alkyl and —O(C1-C6)alkyl;
- R6 is aryl optionally substituted with one or more substituents selected from the group consisting of (C1-C6)alkyl and —O(C1-C6)alkyl;
- R7 is (C1-C10)alkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl(C1-C6)alkyl-, aryl(C1-C6)alkyl- or aryl;
- R8 is an amino acid sidechain;
- and W is a leaving group;
- and wherein the compound of formula 31b is not
A method of preparing a compound of formula 31b:
- or a salt thereof, comprising converting a corresponding compound formula 30b:
- or a salt thereof, to the compound of formula 31b or the salt thereof, wherein R6 is aryl optionally substituted with one or more substituents selected from the group consisting of (C1-C6)alkyl and —O(C1-C6)alkyl;
- R7 is (C1-C10)alkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl(C1-C6)alkyl-, aryl(C1-C6)alkyl- or aryl;
- R8 is an amino acid sidechain;
- and W is a leaving group;
- and wherein the compound of formula 31b is not
A method of preparing a compound of formula 30b:
- or a salt thereof, comprising converting a corresponding compound formula 28b:
- or a salt thereof, to the compound of formula 30b or the salt thereof, wherein Bn is optionally substituted with one or more substituents selected from the group consisting of (C1-C6)alkyl and —O(C1-C6)alkyl;
- R6 is aryl optionally substituted with one or more substituents selected from the group consisting of (C1-C6)alkyl and —O(C1-C6)alkyl;
- R7 is (C1-C10)alkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl(C1-C6)alkyl-, aryl(C1-C6)alkyl- or aryl;
- and R8 is an amino acid sidechain.
Dependencies are inferred from the claim text.