Aminoindanes

US Patent 6,699,909 (March 2, 2004) Assignee Prescient NeuroPharma Inc. 

Phenylsuccinic acid (4.0 g) and 4 ml thionyl chloride were refluxed 30 minutes, 8 ml nitrobenzene and aluminum chloride (4 g) added, and stirred 2 hours at 85 °C. The mixture was poured into 125 ml water, nitrobenzene removed by steam distillation, and the product isolated after re-crystallization in water in 80% yield. H-NMR data supplied. 

The product from Step 1 (1.0 mmol) was dissolved in 20 ml water in a sealed tube containing KCN (1.0mmol) and (NH4)2C03 (2.0mmol) then heated to 90-100°C 16 hours. 

The dark solution was cooled, acidified with 6 M HCl, concentrated, extracted with ethyl alcohol, filtered, and used in Step 3 without further purification. 

The product from Step 2 was refluxed in 45 ml 2 M NaOH 16 hours, cooled, acidified with 6 M HC, and extracted with ethyl alcohol. The mixture was purified by chromatography on Spectrum 1X4 anion exchange resin with dilute HO Ac. The stereoisomers were isolated and re-crystallized in ethyl alcohol/water. H-NMR data for each isomer supplied. 

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Annelated oxazolidines and oxazolines on the basis of d.s-l-aminoindan-2-ol 98S937. 

The feasibility of this approach was demonstrated with a model library of 36 compounds prepared from a combination of three Boc protected L-amino acids (valine 23, phenylalanine 24, and proline 25) and 12 aromatic amines (3,4,5-trimethoxyaniline (26), 3,5-dimethylaniline (27), 3-benyloxyaniline (28), 5-aminoindane (29), 4-tert-butylamline (30), 4-biphenylamine (31), 1-3-benyloxyani-line (28), 5-aminoindane (29), 4-tert-butylaniline (30), 4-biphenylamine (31), 1-aminonaphthalene (32), 4-tritylaniline (33), 2-aminoanthracene (34),... 

Monoamine Oxidases and their Inhibitors. Figure 2 Structures of MAO inhibitors. In the top row, the structural similarity between selegiline/L-deprenyl and methamphetamine is shown. Below are the aminoindan series of propargylamine compounds such as rasagiline. Next, the bifunctional MAO and cholinesterase inhibitors (ladostigil) and lastly, the iron chelator-MAO inhibitors. 

When indan-2-one (3) forms a Schiff s base with aniline and this is reduced with sodium borohydride, the aminoindane 4 is found. The acidic hydrogen is removed with sodium hydride and this is in turn... 

An unusual C-5-alkylation of 6-chlorouracil occurred on attempted displacement of t e chlorine by the aminoindane 70. The reacting species was thought to be the stabi carbonium ion 71, generated by loss of the amino group <06JOC7053>. 

Cheng, H. C., Long, J. P., Nichols, D. E., Barfknecht, C. F., and Rusterholz, D. B. (1974) Effects of rigid amphetamine analogs on vascular strips Studies of 2-aminotetrahydronaphthalene and 2-aminoindane derivatives. Arch. Int. Pharmacodyn. Ther., 208 264-273. 

In another work, a series of substituted 2-aminoindans was analyzed using MM2-85108. The calculated potential energy surface for rotation around the CH—CH—CH2— N and CH—CH2—N—lp in model compound 70 is presented in Figure 9 and shows 9 minima. These were scrutinized as potential candidates for dopamine receptor agonists, according to several criteria The highest-energy conformation f (Erei = 7.3 kcalmol-1)... 

Nucleophilic ring opening of 2-phenyl-5(4//)-oxazolone 146 with (15, 2/f)-l-aminoindan-2-ol provides an amido alcohol that, upon treatment with... 

The constrained bis(oxazolines) 9a and 9b can be constructed beginning with malononitrile 32 as shown by Ghosh and co-workers. Thus, treatment of 32 with anhydrous hydrochloric acid in dioxane, as shown by Lehn and co-workers, yielded imidate salt 33 (Fig. 9.9). Condensation of the imidate salt with commercially available (15,2/ )-l-aminoindan-2-ol afforded the conformationally constrained bis(oxazoline) inda-box 9a. Alkylation at the bridging methylene of 9a was carried out by Davies and co-workers.Treatment of 9a with lithium diisopropylamide followed by alkylation with methyl iodide afforded 9b. Alternatively, alkylation with diiodoalkanes incorporated ring systems at the bridging position (structures 34a-d). 

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