797763-47-4Relevant articles and documents
Radical substitution with azide: TMSN3-PhI(OAc)2 as a substitute of in3
Pedersen, Christian Marcus,Marinescu, Lavinia Georgeta,Bols, Mikael
, p. 816 - 822 (2007/10/03)
TMSN3 and PhI(OAc)2 were found to promote high-yield azide substitution of ethers, aldehydes and benzal acetals. The reaction is fast and occurs at zero to ambient temperature in acetonitrile. However, it is essential for the reaction that TMSN3 is added subsequent to the mixture of PhI(OAc)2 and the substrate. A primary deuterium kinetic isotope effect was found for the azidonation of benzyl ethers both with TMSN3-PhI(OAc)2 and with IN3. Also a Hammett free energy relationship study of this reaction showed good correlation with σ+ constants giving with ρ-values of -0.47 for TMSN 3-PhI(OAc)2 and -0.39 for IN3. On this basis a radical mechanism of the reaction was proposed. The Rayal Society of Chemistry 2005.
Combinatorial synthesis of benztropine libraries and their evaluation as monoamine transporter inhibitors
Pedersen, Hanne,Sinning, Steffen,Buelow, Anne,Wiborg, Ove,Falborg, Lise,Bols, Mikael
, p. 2861 - 2869 (2007/10/03)
A combinatorial synthesis of benztropine analogues is presented. Radical azidonation of 3-benzyloxy-8-azabicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester 3 to 3-(1-azidobenzyloxy)-8-azabicyclo[3.2.1]octane-8- carboxylic acid terf-butyl ester 4 was used as a key step in the synthesis. This step was optimized by adding 10% DMF to the reaction. Reaction of 4 with phenyl magnesium bromide followed by Boc removal and N-methylation gave benztropine 1. Reaction of five-component Grignard reagents with 4 was used to create a two-dimensional library of 25 N-normethylbenztropine analogues. Further reaction of this library with five alkyl bromides was carried out to create a three-dimensional library containing 125 compounds. Screening of the libraries towards binding and inhibition of uptake of the human dopamine (hDAT), serotonin (hSERT) and norepinephrine transporters (hNET) was carried out. None of the synthesized compounds were found to be stronger than benztropine, and none were selective for inhibition of binding over monoamine uptake.
