Abstract
A practical and efficient synthesis of bradykinin B(1) antagonist 1 is described. A convergent strategy was utilized which involved synthesis of three fragments: 3, 6, and 7. Cross coupling of fragments 6 and 7 followed by amidation with 3 enabled efficient synthesis of 1 in 19 steps total, a 35% overall yield from commercially available pyridine 10. The key to the success of the synthesis was the development of a fluorodenitration step to install the fluorine in pyridine 7 and a catalytic enantioselective hydrogenation of N-acyl enamide 9 to set the stereochemistry.
MeSH terms
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Amides / chemical synthesis*
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Amides / chemistry
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Amides / pharmacology
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Amines / chemical synthesis
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Amines / chemistry
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Azoles / chemical synthesis
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Azoles / chemistry
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Boronic Acids / chemical synthesis
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Boronic Acids / chemistry
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Bradykinin B1 Receptor Antagonists*
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Hydrocarbons, Fluorinated / chemical synthesis
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Hydrocarbons, Fluorinated / chemistry
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Hydrogenation
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Methylation
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Pyridines / chemical synthesis*
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Pyridines / chemistry
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Pyridines / pharmacology
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Stereoisomerism
Substances
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Amides
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Amines
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Azoles
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Boronic Acids
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Bradykinin B1 Receptor Antagonists
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Hydrocarbons, Fluorinated
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Pyridines