Triazole-1-carboxylic acid, esters

Intramolecular cycloaddition between an azide and an unsaturated ester (see 300) was the key step in the synthesis of triazole carboxylic acids 302 a, b, prospective anionic sugar mimics (Eq. 33) [79]. 

The direct synthesis of aryl- or alkyl nitriles from cyanide and organohalide precursors is revered in synthetic chemistry, as the nitriles represent a flexible functionality that can easily be converted into (for example) carboxylic acids, esters, amides, amidines, amines and various hetero cycles [67], such as thiazoles, oxazolidones, triazoles and tetrazoles [68]. The tetrazole group... 

SPPS Coupling of Fmoc Amino Acids via l-Hydroxy-lH-l,2,3-triazole-4-carhoxyHc Acid Esters Fmoc amino acid (Immol), l-hydroxy-l//-l,2,3-triazole-4-carboxylic acid ester (Immol) and DIC (Immol) were dissolved in DMF and sonicated for 10 min. The mixture was then added to the resin-bound amino component and the reaction was left for 30-60 min. 

The transformation of an active CH compound into the corresponding diazo derivative with -toluenesulfonyl azide has been designated a diazo transfer reaction and possesses a variety of preparative uses. The method has been useful for the syntheses of diazo derivatives of cyclopentadiene, 1,3-dicar-bonyl compounds, 1,3-disulfonyl compounds,1,3-keto-sulfonyl compounds, ketones, " carboxylic acid esters, and /3-keto imines. Further reaction of these diazo intermediates can lead to azo compounds,"- " 1,2,3-triazoles, and pyrazolinones. ... 

Triazole ring synthesis Carboxylic acid hydrazides f carboxylic acid esters... 

The sulfonamido group is found together with a number of other functional groups in isolated reports. For example, fair yields of 1,2,3-triazoles involving a carboxylic acid ester (Eq. 26), good to excellent yields with a cyano group (Eq. 27), and an old but unexplored reaction leading to an ether substituent (Eq. 28) have been reported. 

Triazole-l-carboxylic acid, 4-aryloxy-, ethyl ester... 

The following compilation shows the results of a reaction sequence consisting of the conversion of carboxylic acids by A -oxalyldiimidazole (A) or A -oxalyld 1,2,4-triazole) (B) into the corresponding azolides followed by acid-catalyzed reaction with alcohols to give the appropriate esters.tl38]... 

Due to its wide application in peptide synthesis, 1-hydroxybenzotriazole 1001 is the most commonly used benzo-triazole derivative with hundreds of references in Chemical Abstracts each year. Utility of compound 1001 comes from its readiness to form esters with carboxylic acids in the presence of dehydrating agents (DAs). Obtained esters 1002 react eagerly with amines to produce amides 1003 in high yields (Scheme 165). More details about this application are given in Section 5.01.12. 

NNN/ 4-methyl-3-phenyl-2-phenylcarbamoyloxy-3//,4//-imidazo[l,Z-b [1,2,4]triazole-3a-carboxylic acid ethyl ester 125 and 4,3a-dimethyl-3-phenyl-2-phenylcarbamoyloxy-3//,4//-imidazo[l,2-A [l,2,4]triazole-6-carboxylic acid methyl ester 126 (Table 27) <2001JOC8528>. 

The synthesis of ethyl ester derivatives of imidazo[5,l-4][l,2,4]triazole-3-carboxylic acid 64 has been reported (Scheme 25) <1999CHE1349>. Starting from the known substituted 5-diazoimidazoles 276, their coupling with malonic acid derivatives afforded the azo compounds 277, which on treatment with triethylamine in DMF, upon prolonged heating time, gave products 64 in moderate yield. 

Ribavirin Ribavirin, l-j3-D-ribofuranosyl-l//-l,2,4-triazol-3-carboxamide (36.1.28), is synthesized by reacting methyl ester of l,2,4-triazol-3-carboxylic acid with 0-l,2,3, 5-tetraacetyl-j3-D-ribofuranose to make methyl ester of l-0-2,3,5-tetraacetyl-j3-D-ribofura-nosyl-l,2,4-triazol-3-carboxylic acid (36.1.27), which is treated with an ammonia solution of methanol to simultaneously dezacylate the carbohydrate part and amidation of the carboxyl part of the product to give ribavirin [29-37]. 

The carboxylic acids of triazoles are readily decarboxylated on heating but are otherwise stable. Esters, amides, nitriles, and hydrazides react normally. This is illustrated in Scheme 18 for the amide and nitrile functions (88JMC330). 

Some relevant substituents are displayed in Table XV. Hydrolysis of esters or nitriles followed by thermal decarboxylation of 2-, 5-, 6-, and 7-carboxylic acids is often used for degradation reactions (61CPB883, 61JCS3046 64UP1). 5-Amino-l,2,4-triazole-3-carboxylic acid is decarbox-ylated in situ by condensation to TP (83S44) TP-5-amideoxime is cyclized to the 5-( 1,2,4-oxadiazol-3-yl) derivative (90EGP282009). 

The amino ester 16 was then hydrolyzed to the carboxylic acid and isolated in 90% yield (Scheme 5.6). Subsequently, the amino acid was coupled with triazole 3 using EDC activation to afford the amide 17 in 90% assay yield. Removal of the chiral auxiliary was achieved via hydrogenolysis using Pd/C or Pd(OH)2 as catalyst to obtain sitagliptin in 83% assay yield. 

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