Pyridine, 2-fluoro-3-iodo

Finally, 2-halopyridines have been reacted with nucleophiles under various conditions <02JHC347>. For example, facile reaction between 2-fluoro, iodo, bromo or chloro pyridine and a variety of nucleophiles (36—>37) can be promoted on brief exposure to microwave heating <02T4931>. 

Pyridine-2,3-dicarboxylic acids containing a halogen in the 5- or 6-position were prepared by oxidation of the corresponding quinolines using either ozone/H202 or catalytic R.UO4. Diacids substituted in the 6-position by Cl or Br, or in the 5-position by F, Cl, or Br, respectively, were isolated in 46-71% yields. The yields of 6-fluoro and 6- or 5-iodo diacids were low (<30%) (Equation 40) <2001S2495>. 

Pyridine and its derivatives react with 1,3-pentadienes forming cyclic products. This type of cyclization was observed by the authors of 95JFC(72)49. They showed that in the reaction of (Z)-1,1,2,5,5,5-hexafluoro-4-phenyl-3-trifluoromethyl-1,3-pentadiene 117 with pyridine the products are [ S,9aR]- and [lS,9tfS]-3-fluoro-9<2-hydro-l,2-bis(trifluoro-methyl)-l-phenyl-4//-quinolizin-4-ones 118 and 119 with 54 and 21% yields, respectively. The structure of the compounds was confirmed by X-ray analysis. Similarly, the reaction of (Z)-l,l,2,5,5,5-hexafluoro-4-iodo-3-trifhioromethyl-l,3-pentadiene 120 with 4-substituted pyridines gives the derivative of 4//-quinolizin-4-one 121 with quinoline, the product is derivative 122. 

On attempting to transform the 6-bromo-6-desoxy or 6-iodo-6-desoxy derivatives of n-glucose into the corresponding 6-fluoro-6-desoxy compounds by means of silver fluoride in pyridine, the loss of hydrogen halide... 

The iodo-fluoro-pyridine 119 is lithiated by LDA to give the only possible lithium derivative 120. But iodine is a poor ortho-director and the compound equilibrates by the halogen dance to put the Li atom next to one of the best orffto-directors fluorine.14 Presumably one molecule of 120 removes I from 119 to give 123 from which the 3-1 atom is removed by another molecule of 120 initiating a chain. 

Later the different iodo/fluoro activity was used in nicotinic acetylcholine receptor (nAChR) PET ligand 447. On the early step of the synthesis starting from 2-fluoro-5-iodopyrunidine 444 the corresponding tiialkyltin heteroaromatic intermediate 445 was obtained based on stanno-Stille coupling in 90 % yield. Further the fluorinated stannate was entered in reaction with iodopyridine 446 leading to cross-coupled pyridine-pyrimidine in 50 % yield. The final step of the synthesis was Boc-deprotection by TEA affording 447 [235] (Scheme 81). 

The most known designer drugs are carphedone 4-chloro-2,5-dimethoxyphenethylamine (2C-C) i 5-6-(5-chloropyridin-2-yl)-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-yM-methylpiperazine-l-carboxylate (zopiclone or Z-drug) 4-(N,N-dimethylamino sulfonyl)-7-fluoro-2,l,3-benzoxadiazole (DBD-F) dimethyltryptamine (DMTA) diphenydramine 4-ethyl-2,5-dimethoxyphenethylamine (2C-E) 4-ethylthio-2,5-dimethoxyphenethylamine (2C-T-2) 4-fluoroamphetamine (4-FMP) indan-2-amine 4-iodo-2,5-dimethoxyphenethylamine (2C-I) 1 -(4-iodo-2,5-dimethoxyphenyl)propan-2-amine (DOI) 4-isopropylthio-2,5-dimethyoxyphenethylamine (2C-T-4) meperidine 2-methylamino-l-(3,4-methylenedioxyphenyl)butan-l-one (Bk-MBDB) l-(3,4-methylenedioxybenzyl)piperazine (MDBP) 1 -(3,4-methylenedioxyphenyl)butan-2-amine (BDB) N-methyl-3,4-methylenedioxymethamphetamine (MMDA-2) N-methyl-1 -(3,4-methylenedioxyphenyl)butan-2-amine (HMDMA) N-methyl-l-(3,4-methylenedioxyphenyl)butan-3-amine (HMDMA) methylphenidate 4-methoxymethamphetamine (PMMA) l-(4-methoxyphenyl)piperazine (4-MPP) 2-(6-methyl-2-p-tolylimidazol[l,2-9]pyridine-3-yl)acetamide (zolpidem) normeperidine 4-phenylbutylamine (4-PBA) 3-phenyl-1-peopyTamine (3-PPA) and 2,4,6-trimethoxyamphetamine (TMA-6). 

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