694-55-3Relevant academic research and scientific papers
A convenient racemic synthesis of two isomeric tetrahydropyridyl alkaloids: Isoanatabine and anatabine
Rouchaud, Anne,Kem, William R.
body text, p. 569 - 581 (2010/09/05)
(Chemical Equation Presented) Anatabine is a major alkaloid in Nicotiana tabacum and its isomer, isoanatabine, was recently found in a marine worm. Reduction of 1-methylpyridinium iodide with sodium borohydride gave 1-methyl-3-piperideine, which was transformed with hydrogen peroxide into the N-oxide. Reaction of the N-oxide successively with trifluoroacetic anhydride and potassium cyanide gave 2-cyano-1-methyl-3-piperideine. Its reaction with 3-pyridylmagnesium chloride gave (±)-N-methyl-isoanatabine. This was transformed with m-chloroperbenzoic acid into the N-oxide which was N-demethylated with iron(II) sulfate, giving (±)-isoanatabine. The successive applications of literature procedures for the N-demethylation by decomposition of N-oxide contributed to the knowledge of the mechanism of this oxidative rearrangement. On the other hand, the reduction of 1-methylpyridinium iodide with sodium borohydride and with potassium cyanide present since the start of the reaction in a two layer ether-water system, gave 2-cyano-1-methyl-4-piperideine. This was transformed into (±)-anatabine by the same sequence of reactions used for the synthesis of (±)- isoanatabine.
PYRROLOTRIAZINE COMPOUNDS AS KINASE INHIBITORS
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Page/Page column 80-81, (2008/06/13)
The present invention provides compounds of formula (I); and pharmaceutically acceptable salts thereof. The formula (I) compounds inhibit tyrosine kinase activity of growth factor receptors such as HER1, HER2 and HER4 thereby making them useful as antiproliferative agents. The formula (I) compounds are also useful for the treatment of other diseases associated with signal transduction pathways operating through growth factor receptors.
Intramolecular cyclization of β-amino and β-ammonio radicals: A new synthetic route to the 1-azabicyclo[3.2.1]octyl- and -[2.2.1]heptyl systems
Della, Ernest W.,Smith, Paul A.
, p. 6627 - 6633 (2007/10/03)
Treatment of 1-(2-phenylselenoethyl)-1,2,5,6-tetrahydropyridine (15) with tributyltin hydride affords only the product of reduction, demonstrating the reluctance of the 5-hexenyl radical 9 to undergo ring closure. When the nature of the radical is modified, either by introduction of an ester group at C4 or via its quaternary ammonium salt, cyclization occurs readily; while the radical 52 gives an excellent yield of 1-methyl-1-azoniabicyclo[3.2.1.]octyl bromide (55) uncontaminated with the product of reduction, the bicyclic product from 21 is accompanied by some reduced material. Production of the unwanted alkene can be eliminated in the latter by recourse to the quaternary ammonium ester 1-(2-bromoethyl)-4-carbethoxy-1-methyl-1,2,5,6-tetrahydropyridinium bromide (35) which, when exposed to tributyltin hydride, affords a 1:1 endo/exo mixture of 4-carbethoxy-1-methyl-1-azoniabicyclo[3.2.1]octyl bromide (37) exclusively. These results support the demonstration of the powerful polar effect of an ester function when attached to the double bond of a 5-hexenyl system, a property which can be exploited in the case of the radical 58. Treatment of the precursor, 1-(2-bromoethyl)-3-carbethoxy-1-methyl-3-pyrrolinium bromide (60), with tributyltin hydride generates 58 which is found to cyclize with high regioselectivity, affording a convenient high-yielding synthesis of the endo/exo isomers of 3-carbethoxy-1-methyl-1-azoniabicyclo[2.2.1]heptyl bromide 57. The isomeric bicyclo[2.2.1]heptyl ester 63 was not detected. These observations are in accordance with predictions based upon frontier molecular orbital considerations.
Synthesis and pharmacological properties of 2-azabicyclooctane derivatives representing conformational restricted isopethidine analogues
Cardellini, Mario,Cingolani, Gian Mario,Claudi, Francesco,Gulini, Ugo,Cantalamessa, Franco,Venturi, Fabrizio
, p. 1 - 4 (2007/10/02)
The synthesis and preliminary pharmacological evaluation of the epimeric 2-methyl-6-phenyl-6-carbethoxy-2-azabicyclooctanes, representing conformationally restricted isopethidine analogues, are reported. 2-azabicyclooctanes / isopethidine analogues / structure-activity relationship
RING INVERSION EQUILIBRIA IN 4-CHLORO-, 4-BROMO-, AND 4-METHOXY-1-ALKYLPIPERIDINES IN A NON-POLAR SOLVENT
Bailey, Judith M.,Booth, Harold,Al-Shirayda, Hatif A.R.Y.,Trimble, Mary L.
, p. 737 - 744 (2007/10/02)
The position of ring inversion equilibrium (axial Requuatorial R) in 4-R-N-alkylpiperidines (R = Cl, Br, or OMe), dissolved in CFCl3-CDCl3, has been determined by (13)C n.m.r. spectroscopy at low temperatures.In all three series, change of NH to NMe produces a marked increase in the proportion of conformation with axial R.When R is OMe, further alterations in the N-substituent from Me to Et, Pri, and CH2CF3 do not affect the equilibrium significantly, but the signifficant changes observed when R is halogen can be related to the inductive effect of the N-substituent. (13)C Chemical shifts, proportions of conformations, and conformational free energy differences are recorded for all systems studied.
Base Catalysed Rearrangements Involving Ylide Intermediates. Part 9. The Rearrangement Reactions of Cyclic Allylic Ammonium and Sulphonium Ylides
Mageswaran, Sivapathasuntharam,Ollis, W. David,Sutherland, Ian O.
, p. 1953 - 1962 (2007/10/02)
The allylic ammonium ylides (22) and (47) and sulphonium ylide (53) are isolable, usually as crystalline solids, because their sigmatropic rearrangements are inhibited by the strain associated with the bicyclic transition state of a concerted reaction mechanism.The tetrahydropyridinium (22) and dihydrothiopyranium (29) ylides undergo a thermal rearrangement, but the pyrrolinium ylide (47) rearranges by a , rather than a , sigmatropic pathway.The dihydrothiophenium ylide (53) does not undergo either a or sigmatropic rearrangement but instead reacts in a bimolecular fashion to give eventually buta-1,3-diene, 2,5-dihydrothiophen, and the heterocycle (55).The rearrangements of the ylides (22) and (29) follow predominantly an endo-pathway leading to a single diastereomer of the products (23) and (31); this strong endo preference is not shown by analogous acyclic ammonium ylides.
