Process for making Hepatitis B core protein modulators
Inventors
Li, Leping • Arnold, Lee D. • Mundla, Sreenivasa Reddy
Assignees
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Publication Number
US-11040965-B2
Publication Date
2021-06-22
Expiration Date
Abstract
The present disclosure provides, in part, a process for preparing compounds (I) having allosteric effector properties against Hepatitis B virus Cp.
Core Innovation
The invention provides a process for preparing a compound represented by Formula I. The process comprises a defined sequence that starts from a compound of Formula II and proceeds through amidation to form Formula III, oxidation to form Formula IV, cyclizing to form a thiazole compound of Formula V, hydrolyzing to form a compound of Formula VI, and coupling the compound of Formula VI with a tricyclic compound of Formula VII to provide the compound of Formula I.
The claim defines that w is 0, 1, or 2, and specifies detailed selection rules for substituents including R1 and R11, and independently selected groups for R2-R8. The invention thereby links the synthesis sequence and coupling between Formula VI and Formula VII to the structural substituent framework that characterizes the Formula I compound.
The disclosure also includes optional amidation of the tricyclic compound of Formula VII to form Formula VIII and named options for coupling, hydrolysis, and cyclization reagents. The overall disclosure associates these routes with the same defined families of structural formulas (Formula I, II-VII, and VIII-XIV) and the specified step transformations within the process.
Claims Coverage
The document includes one independent claim covering a multi-step process to prepare a compound of Formula I from a compound of Formula II via a defined sequence of transformations. The independent claim contains inventive features defined by the ordered sequence of reaction-stage formula conversions and the structural substituent framework (including w and R-group selection) for the resulting Formula I compound.
Defined multi-step conversion from Formula II to Formula I
A process comprising amidating a compound of Formula II to provide a compound of Formula III, oxidizing the compound of Formula III to provide a compound of Formula IV, cyclizing the compound of Formula IV to provide a thiazole compound of Formula V, hydrolyzing the compound of Formula V to provide a compound of Formula VI, and coupling the compound of Formula VI with a tricyclic compound of Formula VII to provide the compound of Formula I.
Structural substituent selection for Formula I (w and R-groups)
The process prepares a compound of Formula I wherein w is 0, 1, or 2, with R1 selected from C1-6 alkyl (optionally substituted with one, two or three halogens), phenyl, and a monocyclic 5-6 membered ring system containing one or more heteroatoms selected from nitrogen, oxygen, and sulfur, and with R11 and R2-R8 each selected according to the specified groups and optional substitution rules.
Across the single independent claim, the coverage centers on an ordered reaction-stage sequence converting Formula II into Formula III, Formula IV, a thiazole compound of Formula V, Formula VI, and finally coupling with a tricyclic compound of Formula VII to yield Formula I, together with the defined substituent constraints for Formula I (including w and the R-group selection rules).
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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