Nucleophilic addition to 3-substituted pyridinium salts: expedient syntheses of (-)-L-733,061 and (-)-CP-99,994.
[reaction: see text] The addition of nucleophiles to 3-substituted pyridinium salts prepared from N-methylbenzamide and various pyridines has been investigated. Good to excellent regioselectivities favoring the 2,3-disubstituted 1,2-dihydropyridines were observed. The resulting 1,2-dihydropyridines led to the corresponding 2,3-disubstituted pyridines upon treatment with Mn(OAc)3/NaIO4. This methodology was also successfully applied to the enantioselective syntheses of (-)-L-733,061 and (-)-CP-99,994, two members of a new class of highly potent, nonpeptide, Substance P antagonists.
Lemire
Alexandre
A
Département de Chimie, Université de Montréal, P.O. Box 6128, Station Downtown, Montréal, Québec, Canada H3C 3J7.
Grenon
Michel
M
Pourashraf
Mehrnaz
M
Charette
André B
AB
D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013373:Substance P / Q000037:antagonists & inhibitors*
D010880:Piperidines; D011726:Pyridinium Compounds; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; C103788:3-((3,5-bis(trifluoromethyl)phenyl)methyloxy)-2-phenylpiperidine; D013373:Substance P