Triazolo pyridine, alkylation

Trazodone Trazodone, 2-[3-[4-(m-chlorophenyl)-l-piperazineyl]propyl]-s-triazolo[4,3-a] piridine-3(2H)-one (7.3.8), is synthesized from 2-chloropiridine, the reaction of which with semicarbazide gives s-triazolo-3-one[4,3-a]pyridine (7.3.7). Alkylation of this product using l-(3-chloropropyl)-4-(3-chlorophenyl)piperazine gives trazodone (7.3.8) [61,62]. 

The bicyclic meso-ionic 3-oxo-l,2,4-triazolo[4,5-a]pyridines (206) have been prepared by the following methods (i) the reaction of the hydrazines (207, X = H) with phosgene, (ii) heating the amide (207, X = CONH2) or the carbamate (207, X = COjEt), and (iii) alkylation or acylation of 3-oxo-l,2,4-triazolo[4,5-a]pyridine (208). The isomeric meso-ionic 2-oxo-l,3,4-triazolo[4,5-a]pyridines (209) are formed from the carbamoyl chlorides (210) and sodium azide. ... 

The only alkyl group reported as reductively removed is the di-phenylmethyl substituent from N3 in compound 165.153 Deoxygenation of N-oxides can be done thermally (heating in toluene with oxygen transfer to solvent) for compounds of type 166,44 or more commonly by use of phosphorus derivatives, as described for compounds 32, 33,45 166,44 and 167.61 Halogens can be reductively removed from [l,2,3]triazolo-[4,5-6]pyridines 160,146 168,220 and 169,142 and from pentachloro derivative 164, giving dichloro compound 170.208 Removal of thiol groups by reduction... 

In an approach to direct C-functionalization of triazolo[4,5-c]pyridines, shown in Scheme 3, 1-methyl (or phenyl)[l,2,3]triazolo[4,5-c]pyridines (26,33) are alkylated exclusively at C-4 by radicals generated by decarboxylation of carboxylic acids (ammonium persulfate-sulfuric acid-silver nitrate) <90ZOB683>. However, with /-butanol various products are obtained depending on the catalyst employed. For example, with ammonium persulfate-sulfuric acid-silver nitrate, exclusive C(4)-methylation (34) was observed, while ammonium persulfate-sulfuric acid gave exclusively C(4)-/ -hydroxy-/ ,/ -dimethylethylation (cf. (36)). The /-butyl analogue (35) was obtained by decarboxylation of pivalic acid. 

Alkenes, perfluoro-cycloadditions to benzyl azide, 60, 35 pyridine imines and ylids, 60, 36 Alkenes, perfluoro-, as heterocyclic precursors, 59, 10 Alkylation, free-radical, of 1,3-dimethyluracil, 55, 227 A-Alkylation, [ 1,2,4]triazolo[ 1,5-u)-pyrimidines, 57, 110 Alkynes, photocycloaddition to uracils, rearrangement with HCNO elimination, 55, 149 Alkynes, ethoxy-, cyclaoddition to hexafluoroacetone azine, 60, 32 Alkynes, perfluoro-, as heterocyclic precursors, 59, 10 Allenes... 

Chloroperoxidase catalysis by, 58, 302 in chlorination of pyrazoles, 57, 337 Chlorophyll, thioaldehyde synthetic intermediate to, 55, 3 Chlorosulfonyl isocyanate, reaction with 2-arylhydrazono-3-oxobutanoate, 59, 148 Chromatography, of [l,2,4]triazolo[l,5-a]-pyrimidines, 57, 106 Chrom-3-enes, see 2//-l-Benzopyrans Chromium tricarbonyl complexes of 3,5-diphenyl-l-(alkyl- or oxido-)-thiabenzenes, 59, 206, 227 indoles, lithiation of, 56, 181, 184 of pyridine, 58, 160 pyridines, lithiation of, 56, 230, 239 of 2f/-thiopyrans, 59, 227 Chromones, see l-Benzopyran-4-ones Cinnamonitrile, a-cyano-, condensations with thio-, seleno-amides, 59, 184, 186 Cinnoline, nitration, MO calculation, 59, 302... 

Table 8 Examples of 3-Alkyl- and 3-Aryl-[l,2,4]triazolo[4,3-a]pyridines Prepared from 2-Hydrazinopyridines and Carboxylic Acids, Anhydrides, Esters or Ortho Esters <66JOC25i, 78JHC439.7OJHC703,70JHC1019)...

Finally, 96 (and its 2-methyl analog), when heated in pyridine with carbon disulfide and triethylamine (bath at 115°C, 6 h), yielded 95% of 7- and 8-methyl-1,6-dihydro-8-azapurine-2-thione. Derivatives of a new ring system were produced instead of azapurines when the 3-methyl and 3-benzyl analogs of 96 were treated similarly, giving 3-alkyl-3,7-dihydro-3//-1,2,3-triazolo[4,5-[Pg.169]

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