Piperidine substituted

Experimentally, it has been shown that the introduction of a heteroatom such as oxygen into the 4-position of piperidine has no appreciable influence on the conformational equilibrium348. Similarly, infrared overtone measurements suggest that in tetrahydro-1,2 oxazine the NH-equatorial conformer predominates349. On the other hand, many piperidines substituted by heteroatoms in the 3 position are found to exhibit a NR axial preference. For example, the preferred conformation for the molecules shown below is NR axial350,35... 

Rudolf, K., Eberlein, W., Dreyer, A., Muller, S.G., Doods, H., Bauer, E. (Boehringer IngelheimJ Preparation of piperidine-substituted amino-acids for use in treatment of CGRP-mediated disorders, W01049676 (2001). 

Tandem radical additions have been used in the preparation of piperidines. Substituted nitrogen containing heterocycles with ring sizes ranging from 5-8 have been synthesized by radical methods [95JCS(P1)19]. Addition of sulfur radicals to 225 occurs selectively at the enamide portion followed by an intramolecular 6-exo cyclization to produce a diastereomeric mixture of 226 in good yield. 

Examination of the properties of N-borane adducts, e.g., 90, of piperidine, substituted piperidines and various other N-containing six-membered ring heterocycles constitutes an alternative approach to variable temperature NMR spectroscopy in that borane can be used as a locking agent for the observation of preferred conformers (cf. Scheme 35). In addition, the adducts can be very helpful for the assignment of the chemical shifts of the other substituents in the molecule as well as to acertain the configuration at the substituted positions (91T6903). 

Phosgene reacts with amidobenzyl piperidines (substituted at the 2-, 3-, or 4- aromatic ring positions) at room temperature to give the corresponding amidobenzyl chlorides, and a substituted urea. The reaction is typified by that shown for the 2-isomer [1179a] ... 

Jiang, J., DeVita, R. J., Goulet, M. T. et al. Syntheses and structure-activity relationship studies of piperidine-substituted quinolones as nonpeptide gonadotropin releasing hormone antagonists. Bioorg. Med. Chem. Lett. 2004,14, 1795-1798. 

A review describing chromone alkaloids is available [600]. Four piperidine substituted chromones and their derivatives are described below. 

NR2 NHalkyl, cycloalkylamine, NHaryl, pyrrolidine, substituted piperidine, substituted morpholine Ar = Ph, 3-Tol, 4-CIC6H4, 4-02NC,6H4, 2-thienyl, 2-pyridyl, 2-naphthyl... 

Phenothiazine derivatives cause postural or orthostatic hypotension. This may be more pronounced in patients with reduced vascular volume resulting from acute hemorrhage or dehydration, and when used with diuretic agents. Hypotension is more frequent with phenothiazine derivatives having either an aliphatic substitution on NIO (e.g., chlorpromazine) or a piperidine substitution on NIO (e.g., mesoridazine or thioridazine). It occurs less frequently with compounds containing a piperazine substitution (e.g., trifluoperazine). The hypotension is due to direct vasodilation and an alpha-adrenergic-receptor-blocking effect. The pressor effects of epinephrine can be reduced, blocked, or reversed by appropriate doses of chlorpromazine. 

Formylation. Vilsmeier formylation reactions have been reviewed. Oxalyl chloride-dimethylformamide has found occasional use one application has been preparation of a piperidine substituted dialdehyde (eq 10). ... 

Scheme 25 Ru-catalyzed C2-arylation/alkylation of pyrrolidines and piperidines substituted at nitrogen with a 2-pyridinyl or 3,4-dihydro-2H-pyrrol-5-yl directing group and removal protocols (2006JA14220, 2013JOC9803).

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