Preparation of a P2X3 antagonist
AssigneeGlaxoSmithKline Intellectual Property (No.3) Limited
InventorsNathalie Chauret, Jeremy Green, David R. Kronenthal, Karine Villeneuve
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Abstract
Described herein are two processes for the preparation of methyl (5)-2-((2-(2,6-difLuoro-4-(methylcarbamol)phenyl)-7-methylimidaz[1,2-a]pyridine-3-yl)methyl)morpholine-4-carboxylate, a P2X3 antagonist, in a stepwise manner and chemical intermediates used in the synthetic processes.
Claims17
A process for the preparation of methyl (S)-2-((2-(2,6-difluoro-4-(methylcarbamoyl)phenyl)-7-methylimidazo[1,2-a]pyridin-3-yl)methyl)morpholine-4-carboxylate (Compound 1):
- comprising contacting a compound with the structure:
- with an amide coupling reagent and methylamine or a salt of methylamine.
A process for the preparation of methyl (S)-2-((2-(2,6-difluoro-4-(methylcarbamoyl)phenyl)-7-methylimidazo[1,2-a]pyridin-3-yl)methyl)morpholine-4-carboxylate (Compound 1), comprising:
- A) the reaction of a compound with the structure:
- with 2,2,6,6-tetramethylpiperidine 1-oxyl or T3P to produce a compound with the structure:
- B) followed by the reaction of the compounds with the structures:
- with potassium carbonate and potassium bicarbonate to produce a compound with the structure:
- C) followed by the reaction of the compound with the structure:
- with palladium on carbon and hydrogen to produce a compound with the structure:
- D) followed by the reaction of the compound with the structure:
- with hydrogen chloride in ethyl acetate to produce a compound with the structure;
- E) followed by the reaction of the compound with the structure:
- with methyl chloroformate and sodium bicarbonate to produce a compound with the structure:
- F) followed by the reaction of the compound with the structure:
- with N-bromosuccinimide and acid to produce a compound with the structure:
- G) followed by the reaction of the compound with the structure:
- with 2-amino-4-methylpyridine and optionally sodium borohydride to produce a compound with the structure:
- H) followed by the reaction of the compound with the structure:
- with carbonyldiimidazole and methylamine to produce a compound with the structure:
Dependencies are inferred from the claim text.