Triazole intermediate

Ethyl 3-azido-l-methyl-177-indole-2-carboxylate 361 is prepared in 70% yield by diazotization of amine 360 followed by substitution of the created diazonium group with sodium azide. In cycloadditions with nitrile anions, azide 361 forms triazole intermediates 362. However, under the reaction conditions, cyclocondensation of the amino and ethoxycarbonyl groups in 362 results in formation of an additional ring. This domino process provides efficiently 4/7-indolo[2,3-i ]l,2,3-triazolo[l,5- ]pyrimidines 363 in 70-80% yield (Scheme 57) <2006TL2187>. 

In a similar tandem reaction, ethyl 2-azido-l-methyl-l/7-indole3-carboxylate 364 is converted to indolo[3,2- ]l,2,3-triazolo[l,5- ]pyrimidin-5-ones 366 via triazole intermediates 365 that are not separated (Scheme 58). Products 366 are obtained in 80-90% yield as potential intercalates of DNA <2003H(60)2669>. 

Alternatively, the triazole intermediate may be assembled via a 1,3-dipolar cycloaddition of the enol and mesyl azide ... 

Active methylene nitriles condense with o-substituted aryl and heteroaryl azides in a two-step process to give tricyclic triazolopyrimidines without isolation of the triazole intermediates <85BSB441, 87BSB587). 5-Azido-4-formyltriazoles (758) condense with dimethyl 3-oxopentanedioate and tri-ethylamine in ethanol to give 5-(triazol-l-yl)-4-formyltriazoles (759), which undergo cyclization to... 

Reaction between trichloroacetonitrile and Ph2CN2 at low temperatures yields 67 other electron-deficient nitriles give different products. It is possible that the reaction proceeds via an unstable 3//-1,2,4-triazole intermediate, which loses N2 to form a nitrile ylide before adding a second mole of nitrile as in Scheme 13. 

The triazolines (97), were synthesized from the triazolinethione (95) by oxidation to the sulfonic acid and subsequent treatment with H20 and HC1 at 20-100° [95EUP657437], The 1,2,4-triazole intermediate (98), prepared from the N-unsubstituted triazole by reaction with 4-MeOC6H4CH,Cl and KjCO, with tetrabutylammionium hydrosulfate for 3 h at 60°, was further elaborated to chiral crown ether macrocycles [94S1091]. 

The reaction of readily available triazole intermediates 115 with amines provides a new synthetic route to the [l,2,3]triazolo[l,5-a][l,4]benzodiazipine cores 114 and 116, closely related to the core of anxiolytic agents alprazolam and estazolam <07TL3495>. 

Derivatives of the single step product are used in the preparation of 4-carboxy-1,2,3-triazole intermediates, (I), the latter which is used to prepare benzazepine and benzoth-iazepine derivatives (2). Prior to the current invention, the key intermediate was prepared in a two step process illustrated in Eq. 1 ... 

In an attempt to study triazole analogs of the a-amino adds as an-timetabolites, Sheehan and Robinson prepared alanine containing such a substituent (1.3-3) along with a series of 4-substituted 1,2,3-triazole intermediates. The best route (Eq. 30) was discovered after several alternatives were investigated. 

From Carboxylic Acids and Derivatives.—A novel method has been reported for the degradation of a-unbranched carboxylic acids into aldehydes containing one carbon atom less through the formation of triazole intermediates (Scheme 3)."... 

The reaction of sulfonyl azides with terminal alkynes is an interesting exception. Whereas aryl and alkyl azides react with activated alkynes to give the corresponding 1,2,3-triazoles, intermediate sulfonyltriazoles result in the formation of different products. In the presence of amines, N-sulfonyl azides are converted to M-sulfonyl amidines, whereas under aqueous conditions, M-acylsulfonamides are the major products [76-78]. Nevertheless, Fokin et al. reported conditions for the successful formation of N -sulfonyl-1,2,3-triazoles 105 shown in Scheme 22 [79]. 

Davies et al. developed a three-step synthesis of2,3-fiised pyrroles from cyclic ketones. Enone 30 was converted to the corresponding triflate and coupled with ethynylmagnesium bromide to furnish 31 in 71% yield. Exposure of 31 to tosylazide and CuTc formed the expected triazole intermediate addition of Rh2(esp)2 catalyzed the formation of complex pyrrole 32. The reaction is generally high yielding and tolerant of a wide variety of substrates (13JA11712). 

In this polymerization, the click reaction of diyne 9 and sulfonyl azide 10 first takes place to form triazole intermediate A. The highly reactive ketenimine species B is then formed via ring opening of the triazole A, followed by nucleophilic attack of diamine 11 to afford polyamidines (Scheme 6). The nucleophilic attack readily occurs regardless of the electronic and steric nature of the diamines, which provides a great opportunity for other nucleophiles such as diols to react. If diols are used as alternative nucleophiles instead of diamines in this MCP, polyimidates are formed instead of polyamidines. 

Scheme 6 Reaction pathways of copper(I)-catalyzed multicomponent polymerization of diynes 9, sulfonyl azides 10, and diamines 11 or diols 12 A triazole intermediate, B ketenimine species, C N-sulfonyl amide...

Three-component reaction of 2-ethynylaniline, sulfonyl azide, and nitroolefin also could lead to polysubstituted indole derivatives in moderate to good yields with CuBr catalyst. The reaction conditions are extremely mild and various polysubstituted indoles were obtained successfully. Initially, a triazole intermediate was formed from alkyne and sulfonyl azide in the presence of CuBr and triethy-lamine. It could convert into reactive ketenimine by the ring-opening rearrangement. Subsequently intramolecular nucleophilic addition, intermolecular Michael addition, and tautomerization could lead to the desired polysubstituted indoles [49] (Scheme 8.20). 

The fused indoUnes could be synthesized from 2-ethynylarylmethylenecyclo-propane with sulfonyl azide using Cul as catalyst and EtgN as base. A ketenimine species and 6zr-electrocyclization could be involved for this transformation. The copper-catalyzed triazole intermediate formation from 2-ethynylaryl... 

A number of 3-triazolyl-2-iminochromenes were synthesized with Cul catalyst through three-component condensation. Initially, a Cul-catalyzed cycloaddition between 2-azidoacetonitrile and an acetylene could lead to a triazole intermediate. 

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