Pyridine → N,N'-Dodecanediyl-bis-pyridinium dibromide

Compounds 1-3 (FIG. 3) were prepared by reacting S-(−)-nicotine with the appropriate n-alkyl iodide in glacial acetic acid, utilizing the procedure described by Crooks, et al., Drug Dev. Res. 1995, 36, 91-102. The N-n-alkylpyridinium salts 4-7 (FIG. 3) were obtained via n-alkylation of pyridine with the appropriate n-alkyl halide. The conformationally restricted racemic syn- and anti-nicotine analogs 8-12 and 13-17, respectively (FIG. 3), were prepared via regiospecific alkylation of the pyridine-N atom of the corresponding free base. The syn-free base was synthesized from 7-aza-1-tetralone, and the anti-free base was prepared from 5-aza-1-tetralone. N,N′-Dodecanediyl-bis-nicotinium dibromide, 18 (FIG. 4), was prepared by dissolving S-(−)-nicotine in glacial acetic acid, stirring the mixture for five minutes and then adding dibromododecane. The solution was stirred under reflux for three days, the solvent was evaporated under reduced pressure, and the resulting residue was treated with an aqueous saturated solution of NaHCO3. The resulting mixture was then extracted with diethyl ether (3×50 mL), and then with chloroform (3×50 mL). The aqueous layer was collected and lyophilized for 24 hours, and the resulting solid was triturated with chloroform. After filtration, the filtrate was dried over anhydrous MgSO4 and removal of solvent afforded the bis-nicotinium salt, 18. N,N′-Dodecanediyl-bis-pyridinium dibromide, 19 (FIG. 4) was prepared by reacting an excess of pyridine with dibromododecane for 24 hours at 65° C. in the absence of solvent. The resulting solid was collected by filtration, dissolved in water, and the aqueous solution washed with diethyl ether (3×50 mL). The aqueous solution was then lyophilized to afford 19 as a crystalline solid.

1. customfor 24 hours
2. customat 65° C.
3. filtrationThe resulting solid was collected by filtration
4. dissolutiondissolved in water
5. washthe aqueous solution washed with diethyl ether (3×50 mL)

ORD-Eintrag

ord-db999f8d63b54256a715e8cb9a57acbb

Quelldatensatz

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08546415B2