179120-92-4Relevant articles and documents
A six-step synthesis of (S)-5-ethenyl-3-(1-methyl-2-pyrrolidinyl)pyridine (SIB-1508Y) from (S)-nicotine
Comins, Daniel L.,Smith, Emilie D.
, p. 1449 - 1451 (2006)
The anti-Parkinson's agent SIB-1508Y was prepared in six steps from (S)-nicotine in 20% overall yield. The strategy involves a regioselective formylation at C-5 of a 1,4-dihydronicotine intermediate.
Enantioselective, palladium-catalyzed α-arylation of N-Boc pyrrolidine: In situ react IR spectroscopic monitoring, scope, and synthetic applications
Barker, Graeme,McGrath, Julia L.,Klapars, Artis,Stead, Darren,Zhou, George,Campos, Kevin R.,O'Brien, Peter
experimental part, p. 5936 - 5953 (2011/10/09)
A comprehensive study of the enantioselective Pd-catalyzed α-arylation of N-Boc pyrrolidine has been carried out. The protocol involves deprotonation of N-Boc pyrrolidine using s-BuLi/(-)-sparteine in TBME or Et2O at -78 °C, transmetalation with ZnCl2 and Negishi coupling using Pd(OAc)2, t-Bu3P-HBF4 and the aryl bromide. This paper reports several new features including in situ React IR spectroscopic monitoring of the process; use of (-)-sparteine and the (+)-sparteine surrogate to access products with opposite configuration; development of a catalytic asymmetric lithiation-Negishi coupling reaction; extension to a wide range of heteroaromatic bromides; total synthesis of (R)-crispine A, (S)-nicotine and (S)-SIB-1508Y via short synthetic routes; and examples of α-vinylation of N-Boc pyrrolidine using vinyl bromides exemplified by the total synthesis of naturally occurring (+)-maackiamine (thus establishing its configuration as (R)). In this way, the full scope and limitations of the methodology are delineated.
Expedient five-step synthesis of SIB-1508Y from natural nicotine
Wagner, Florence F.,Comins, Daniel L.
, p. 8673 - 8675 (2007/10/03)
Altinicline (SIB-1508Y), an anti-Parkinson's agent, was prepared in five steps from natural nicotine in 32% overall yield via a regioselective substitution of the pyridine ring of (S)-nicotine.
Synthesis of nicotine derivatives from nicotine
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Page/Page column 8; 10, (2008/06/13)
Methods of synthesizing nicotine analogs and derivatives are described. In some embodiments the methods utilize an alkyl or aryl silyl-substituted nicotine analog intermediate. Intermediates useful for the synthesis of nicotine and nicotine analogs are al
The first enantioselective synthesis of (S)-5-bromo-3-(1-methyl-2-pyrrolidinyl)pyridine: A key intermediate for the preparation of SIB-1508Y
Felpin, Francois-Xavier,Vo-Thanh, Giang,Villieras, Jean,Lebreton, Jacques
, p. 1121 - 1124 (2007/10/03)
The first enantioselective synthesis of (S)-5-bromo-3-(1-methyl-2-pyrrolidinyl)pyridine is described via intramolecular hydroboration-cycloalkylation of an azido-olefin intermediate. The chiral homoallylic alcohol was efficiently synthesized by enantioselective reduction of the corresponding ketone using (+)-diisopinocamphenylchloroborane as the key reaction. The total synthesis of (S)-SIB-1508Y was achieved with an enantiomeric excess (e.e.) of 94% in ten steps and in 18% overall yield from the commercially available 5-bromo-3-pyridinecarboxylic acid.
A Practical and Efficient Synthesis of the Selective Neuronal Acetylcholine-Gated Ion Channel Agonist (S)-(-)-5-Ethynyl-3-(1-methyl-2-pyrrolidinyl)pyridine Maleate (SIB-1508Y)
Bleicher, Leo S.,Cosford, Nicholas D. P.,Herbaut, Audrey,Stuart McCallum,McDonald, Ian A.
, p. 1109 - 1118 (2007/10/03)
An efficient, high-yielding synthetic procedure for the preparation of the novel neuronal acetylcholinegated ion channel agonist (S)-(-)-5-ethynyl-3-(1-methyl-2-pyrrolidinyl)pyridine maleate [(S)-2, SIB-1508Y] is described. The key steps in the process include the lithium bis(trimethylsilyl)amide-mediated acylation of N-vinylpyrrolidinone with ethyl 5-bromonicotinate, a high-yielding sodium borohydride reduction of imine 5, and a new heteroaryl-alkyne cross-coupling protocol for the introduction of the ethyne moiety in (S)-2. The preparation of enantiomerically pure (S)-2 was accomplished via a combination of enantioselective reduction of imine 5 and crystallization of enantiomerically enriched 5-bromo-3-(1-methyl-2-pyrrolidinyl)pyridine (7) as the dibenzoyl-L-tartaric acid salt.
