70263-44-4

Upstream product

• 70263-43-3 1-(4-Bromophenyl)-1-(3-pyridyl)-2-propen-1-ol 
• 14548-45-9 (4-bromophenyl)-pyridin-3-yl-methanone 
• 54950-20-8 methyl nicotinoylacetate 
• 77470-73-6 (Z)-3-(4-bromophenyl)-3-(3-pyridinyl)prop-2-en-1-ol 
• 126629-81-0 methyl 3-(4-bromophenyl)-3-oxopropanoate 

Downstream Products

• 56775-88-3 Zimelidine 
• 60324-59-6 Nomelidine 
• 79567-85-4 (Z)-3-(4-cyanophenyl)-N,N-dimethyl-3-(3-pyridyl)allylamine 

Relevant academic research and scientific papers

(E)-,(Z)-parallel preparative methods for stereodefined β,β-diaryl- and α,β-diaryl-α,β-unsaturated esters: Application to the stereocomplementary concise synthesis of zimelidine

Parallel and practical methods for the preparation of both (E)- and (Z)-β-aryl1-β-aryl2-α,β-unsaturated esters 1 and (E)- and (Z)-α-aryl1-β-aryl2-α,β-unsaturated esters 2 are described. These methods involve accessible, robust, stereocomplementary N-methylimidazole (NMI)-mediated enol tosylations (14 examples, 70-99 % yield), as well as stereoretentive Suzuki-Miyaura cross-couplings (36 examples, 64-99 % yield). The highlighted feature of the present protocol is the use of parallel and stereocomplementary approaches to obtain highly (E)- and (Z)-pure products 1 and 2 by utilizing sequential enol tosylations and cross-coupling reactions. An expeditious and parallel synthesis of (E)- and (Z)-zimelidine (3), which is a highly representative selective serotonin reuptake inhibitor (SSRI), was performed by utilizing the present methods.

Synthesis of pyridylallylamines related to zimelidine and their inhibition of neuronal monoamine uptake

Analogues of the antidepressant agent zimelidine [6, (Z)-3-(4-bromophenyl)-N,N-dimethyl-3-(3-pyridyl)allylamine], a selective inhibitor of neuronal 5-hydroxytryptamine reuptake, were synthesized by several routes with the aim of obtaining compounds having a cis configuration (with respect to pyridyl and allylamine). Two methods utilized suitably substituted benzoylpyridines as starting materials. In two other routes, the bromine in 6 was either directly displaced (CN) or converted via the corresponding lithio derivative to H, Cl, I, Me, SiMe3. The configurations were determined by UV, 1H NMR and lanthanide-induced shifts in 1H NMR. The compounds were evaluated as uptake inhibitors by measuring the accumulation of [3H]noradrenaline and 5-hydroxyl[14C]tryptamine in mouse brain slices (in vitro and in vivo). Para substitution favored 5-hydroxytryptamine activity and ortho substitution favored NA activity in the cis series. The in vitro effect on 5-hydroxytryptamine was rather insensitive to variations in the para substituent, whereas pronounced effects in vivo were observed only with Cl, Br (6), and I.