40023-80-1

Usage

InChI:InChI=1/C11H17NO/c1-4-11(12-2)9-5-7-10(13-3)8-6-9/h5-8,11-12H,4H2,1-3H3

Upstream product

• 97-94-9 triethyl borane 
• 13114-23-3 4-methoxybenzyl-N-methylimine 
• 123-11-5 4-methoxy-benzaldehyde 
• 74-89-5 methylamine 
• 121-97-1 4-Methoxypropiophenone 
• 2749-94-2 1-methoxy-4-(prop-1-yn-1-yl)benzene 

Relevant academic research and scientific papers

Discovery of an Orally Bioavailable, Brain-Penetrating, in Vivo Active Phosphodiesterase 2A Inhibitor Lead Series for the Treatment of Cognitive Disorders

Herein, we describe the discovery of a potent, selective, brain-penetrating, in vivo active phosphodiesterase (PDE) 2A inhibitor lead series. To identify high-quality leads suitable for optimization and enable validation of the physiological function of PDE2A in vivo, structural modifications of the high-throughput screening hit 18 were performed. Our lead generation efforts revealed three key potency-enhancing functionalities with minimal increases in molecular weight (MW) and no change in topological polar surface area (TPSA). Combining these structural elements led to the identification of 6-methyl-N-((1R)-1-(4-(trifluoromethoxy)phenyl)propyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (38a), a molecule with the desired balance of preclinical properties. Further characterization by cocrystal structure analysis of 38a bound to PDE2A uncovered a unique binding mode and provided insights into its observed potency and PDE selectivity. Compound 38a significantly elevated 3′,5′-cyclic guanosine monophosphate (cGMP) levels in mouse brain following oral administration, thus validating this compound as a useful pharmacological tool and an attractive lead for future optimization.

Multicomponent C-alkylation reactions of aromatic aldimines with trialkylboranes reagents

The one-pot three-component reaction of an aryl aldehyde, an arylamine, and a trialkylborane in the presence of hydrogen peroxide afforded the alkylated arylamines 1 in good yields via oxidized imine-borane complexes. In addition, the versatility of our procedure has been confirmed by the use of enolizable aldehydes, alkylic amines, and cyclic imines.

Ind2TiMe2-catalyzed addition of methyl- and ethylamine to alkynes

We describe a very simple hydrogenation-like experimental protocol for the addition of gaseous methyl- and ethylamine to alkynes in the presence of Ind2TiMe2 as the catalyst. For efficient hydroamination reactions it is sufficient to stir a mixture of the alkyne and the catalyst in toluene at temperatures between 80°C (terminal alkynes) and 105°C (internal alkynes) under a constant pressure of 1 atm of the corresponding amine. After subsequent reduction of the initially formed imines, methyl- and ethylamine derivatives are the final products of the described one-pot reaction sequences. In the case of 2-alkyl-1-phenylalkynes as starting materials, biologically interesting 2-phenylethylamine derivatives possessing a small methyl or ethyl substituent at the N atom are easily accessible by the new reaction protocol. Wiley-VCH Verlag GmbH & Co. KGaA, 2005.