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US 8,129,561 B2Granted
Processes for intermediates for macrocyclic compounds
AssigneeTranzyme Pharma Inc.
InventorsEric Marsault, Luc Ouellet, Hamid R. Hoveyda
Life of this patent
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Abstract
The present invention is directed to novel macrocyclic compounds of formula (I) and their pharmaceutically acceptable salts, hydrates or solvates: wherein R1, R2, R3, R4, R5, R6, n1, m, p Z1, Z2, and Z3 are as describe in the specification. The invention also relates to compounds of formula (I) which are antagonists of the motilin receptor and are useful in the treatment of disorders associated with this receptor and with or with motility dysfunction.
Claims28
A process for preparing a compound of formula (I):
- wherein R1 is C1-C4 alkyl;
- the process comprising:
- (a) contacting a compound of formula (A):
- with a compound of formula (B):
- in the presence of an azodicarboxylate reagent and a phosphine reagent, or in the presence of a combined Mitsunobu reagent, to form a compound of formula (C):
- wherein X is halogen or triflate and PG2 is an ester protecting group;
- (b) contacting the compound of formula (C) with a reducing agent to form a compound of formula (D):
- (c) contacting the compound of formula (D) with a compound of formula (E):
- in the presence of a palladium catalyst, optionally a copper salt and/or optionally an organic base to form a compound of formula (F):
- wherein PG1 is hydrogen or an amine protecting group;
- (d) contacting the compound of formula (F) with hydrogen in the presence of a metal catalyst to form the compound of formula (G):
- (e) removing the PG1 protecting group, when present, from the compound of formula (G) to provide the compound of formula (I).
9 more elements
Dependencies are inferred from the claim text.