Benzodioxan, 2-aminomethyl

Finally, very recently Pallavicini et al., in continuation of a previous study on ortho-monosubstituted compounds, designed and synthesized a series of 2-[(2-phenox-yethyl) aminomethyl]-l,4-benzodioxanes ortho-disubstituted at the phenoxy moiety [99]. The disubstituted analogues were tested for their binding affinities at the three oq-AR subtypes and for the 5-HT1A-R. The affinity values of the new compounds were compared with those of the enantiomers of the 2,6-dimethoxyphenoxy analogue, the well-known oq-AR antagonist WB-4101 (Scheme 8.1), and of the ortho-monosubstituted derivatives. The results suggested some distinctive aspects in the interaction of the phenoxy moiety of monosubstituted and disubstituted compounds with the cqa-AR and the 5-HTiA receptors. A classical (Hansch) QSAR analysis was applied to the whole... 

The affinity of phenoxyethylamines for adrenergic receptor sites is enhanced by cyclization to analogous aminomethyl-1,4-benzodioxans such as pjperoxan (XLVI, R R = (CHjIs) which block a-receptors [240]. 

The introduction of guanidine [94,138, 252, 254] and quaternary ammonium [94] groups into 2-aminomethyl-l,4-benzodioxan leads to compounds with adrenergic neurone blocking properties similar to those of guanethidine and the... 

Aminomethyl-l,4-benzodioxane p-Methoxyethoxy ethyl chloride Potassium carbonate... 

Aminomethyl-l,4-benzodioxane (17 g) and p-methoxyethoxy ethyl chloride (7 g) were heated at 160°C for 2 hours. The reaction mixture was cooled and chloroform (30 ml) and a solution of potassium carbonate (7 g) in water (20 ml) added thereto.The chloroform layer was removed and the aqueous layer extracted twice with chloroform (10 ml each time). The chloroform extracts were combined and dehydrated over anhydrous sodium sulfate. Filtration, followed by distillation gave 2-(p-methoxyethoxyethyl)amino-methyl-l,4-benzodioxane (yield 7.7 g) as a pale yellow oil boiling at 180-186°C/11.5 mm. 

Aminomethyl-l,4-benzodioxane S-Methylisothiouronium sulfate Sodium hydroxide o-Dihydroxybenzene... 

Repinotan (392) is a 5-HTla agonist, in which the 2-(aminomethyl)-l,4-benzodioxan group bioisosterically replaces the arylpiperazine. Repinotan is being developed by Bayer as a potential treatment for ischemic stroke and traumatic brain injury [128]. 

Figure 9.9 Synthesis of 2-[2-(2,6-dimetho3q heno3g )ethyI]aminomethyl-l,4-benzodioxane including the information given in the paper to elucidate greenness of the s)mthetie path. THF tetrahydrofuran DMSO dimethyl sulfoxide DCM dichloromethane.

---