960595-11-3

Upstream product

• 17150-62-8 N-benzyl-3-butenylamine 
• 108-24-7 acetic anhydride 
• 103-49-1 dibenzylamine 
• 100-46-9 benzylamine 
• 75-36-5 acetyl chloride 

Downstream Products

• 960594-94-9 2-benzyl-1-methyl-2-azabicyclo[3.1.0]hexane 
• 1374247-16-1 N-benzyl-N-(1-cyclopentylethyl)but-3-en-1-amine 
• 1374247-17-2 N-benzyl-N-(1-cyclohexylethyl)but-3-en-1-amine 
• 1374247-10-5 N-benzyl-N-(but-3-en-1-yl)ethanethioamide 
• 67077-43-4 hex-3-ene-1,6-diol 
• 4783-65-7 N-benzyl-2-piperidinone 
• 108303-99-7 (R,S)-3-methyl-1-phenylmethyl-2-pyrrolidinone 

Relevant academic research and scientific papers

Discovery and Development of 3-(6-Chloropyridine-3-yloxymethyl)-2-azabicyclo[3.1.0]hexane Hydrochloride (SUVN-911): A Novel, Potent, Selective, and Orally Active Neuronal Nicotinic Acetylcholine α4β2 Receptor Antagonist for the Treatment of Depression

A series of chemical optimizations guided by in vitro affinity at the α4β2 receptor in combination with selectivity against the α3β4 receptor, pharmacokinetic evaluation, and in vivo efficacy in a forced swim test resulted in identification of 3-(6-chloropyridine-3-yloxymethyl)-2-azabicyclo[3.1.0]hexane hydrochloride (9h, SUVN-911) as a clinical candidate. Compound 9h is a potent α4β2 receptor ligand with a Ki value of 1.5 nM. It showed >10 μM binding affinity toward the ganglionic α3β4 receptor apart from showing selectivity over 70 other targets. It is orally bioavailable and showed good brain penetration in rats. Marked antidepressant activity and dose-dependent receptor occupancy in rats support its potential therapeutic utility in the treatment of depression. It does not affect the locomotor activity at doses several folds higher than its efficacy dose. It is devoid of cardiovascular and gastrointestinal side effects. Successful long-term safety studies in animals and phase-1 evaluation in healthy humans for safety, tolerability, and pharmacokinetics paved the way for its further development.

Synthesis of substituted γ- And δ-lactams based on titanocene(III)-catalysed radical cyclisations of trichloroacetamides

A new procedure for the synthesis of γ- and δ-lactams based on a Cp2TiCl-catalysed cyclisation of trichloroacetamides under mild reaction conditions is reported. Theoretical studies supported the observed regioselectivity in the cyclisations and the mechanism involved in the dehalogenation process.

Reductive alkylation of thioamides with Grignard reagents in the presence of Ti(O i Pr)4: Insight and extension

The reductive alkylation of thioamides by Grignard reagents in the presence of Ti(OiPr)4 is the subject of a study involving 20 different substrates. The influence of various parameters has been evaluated, showing notably that the yields of this moderately efficient process can be improved in several cases by applying a slow addition of the Grignard reagent. The results presented in this contribution also provide new insight into the reactivity of the proposed key intermediates, namely, a metalated iminium species and, ultimately, an α-metalated amine. Interestingly, by control of the temperature and the amount of Grignard reagent engaged, the reaction can be directed toward the selective formation of the former titanium intermediate complex. This represents an extension of the original method, allowing the synthesis of various previously inaccessible substituted amines by subsequent addition of a nucleophilic reagent. This role can be played not only by organomagnesium compounds but also by alkyllithium reagents, alkyltitanium(IV) complexes, and lithium aluminum hydride. The properties of the α-metalated amine final intermediate have also been explored, demonstrating that this complex is a poor nucleophile but can act as a radical precursor, which is especially evidenced when the resulting radical species are stabilized. Overall, this chemistry thus proves unexpectedly rich and can plausibly lay the basis for the development of new applications in the future.

Kulinkovich-type reactions of thioamides: Similar to those of carboxylic amides?

The behaviour of thioamides under Kulinkovich-type conditions is compared with the known reactivity of carboxylic amides. Dramatic differences are disclosed. The Royal Society of Chemistry 2012.