Alvameline (Lu 25-109) is a M₁

receptor Receptor may refer to: * Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...

agonist and M₂/ M₃

antagonist that was under investigation for the treatment of Alzheimer's disease, but produced poor results in

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, diet ...

s and was subsequently discontinued.

Synthesis

Alkylation of

nicotinonitrile Nicotinonitrile or 3-cyanopyridine is an organic compound with the formula NCC5H4N. The molecule consists of a pyridine ring with a nitrile group attached to the 3-position. A colorless solid, it is produced by ammoxidation of 3-methylpyridine ...

(accessible from

nicotinamide Niacinamide or Nicotinamide (NAM) is a form of vitamin B3 found in food and used as a dietary supplement and medication. As a supplement, it is used by mouth to prevent and treat pellagra (niacin deficiency). While nicotinic acid (niacin) may ...

) (1) with methyl iodide affords the ''N''-methylpyridinium salt (2). The reduction of this intermediate with

sodium borohydride Sodium borohydride, also known as sodium tetrahydridoborate and sodium tetrahydroborate, is an inorganic compound with the formula Na BH4. This white solid, usually encountered as an aqueous basic solution, is a reducing agent that finds applica ...

gives 3-cyano-''N''-methyl-1,2,5,6- tetrahydropyridine 657-66-9(3). Reaction with

ethyl chloroformate Ethyl chloroformate is the ethyl ester of chloroformic acid. It is a reagent used in organic synthesis for the introduction of the ethyl carbamate protecting group and for the formation of carboxylic anhydrides. Preparation Ethyl chloroform ...

results in ''N''-demethylation and consequent formation of the corresponding carbamate 20241-16-9(4). The nitrile group is then transformed to a

tetrazole Tetrazoles are a class of synthetic organic heterocyclic compound, consisting of a 5-member ring of four nitrogen atoms and one carbon atom. The name tetrazole also refers to the parent compound with formula CH2N4, of which three isomers can be fo ...

by reaction with sodium azide in the presence of

aluminum chloride Aluminium chloride, also known as aluminium trichloride, is an inorganic compound with the formula . It forms hexahydrate with the formula , containing six water molecules of hydration. Both are colourless crystals, but samples are often contam ...

givin
CID:9991151
(5). The surrogate acid is then alkylated with

ethyl iodide Ethyl iodide (also iodoethane) is a colorless flammable chemical compound. It has the chemical formula C2H5I and is prepared by heating ethanol with iodine and phosphorus.''Merck Index of Chemicals and Drugs'', 9th ed., monograph 3753 On contact ...

to affor
CID:10106197
(6). Treatment with acid then removes the carbamate on the ring nitrogen giving Lu-25-077 21549-70-8(7). The methyl group on the

piperidine Piperidine is an organic compound with the molecular formula (CH2)5NH. This heterocyclic amine consists of a six-membered ring containing five methylene bridges (–CH2–) and one amine bridge (–NH–). It is a colorless liquid with an odor de ...

ring restored using

formaldehyde Formaldehyde ( , ) (systematic name methanal) is a naturally occurring organic compound with the formula and structure . The pure compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde (refer to section ...

and formic acid under standard Eschweiler–Clarke conditions, yielding alvameline (8).

References

{{Muscarinic acetylcholine receptor modulators Muscarinic agonists Tetrahydropyridines Tetrazoles

Synthesis

See also

References