Terminal lipophilization of a unique DNA dodecamer by various nucleolipid headgroups: Their incorporation into artificial lipid bilayers and hydrodynamic properties

• Emma Werz and
• Helmut Rosemeyer

Beilstein J. Org. Chem. 2015, 11, 913–929, doi:10.3762/bjoc.11.103

• positions of the pyrimidine β-D-ribonucleosides uridine (1, R = H), 5-methyluridine (2, R = CH3) and 5-fluorouridine (3, R = F) which were lipophilized by different hydrophobic residues. The following formulae (Figure 2) show the six nucleolipids 4a–9a [13][14][15][16][17], which designate that mono

• -, sesqui-, and diterpenes as well as single and double-chained alkyl groups (completed by an alicyclic alkyl group), have been introduced for the lipophilization of the pyrimidine nucleosides. The resulting nucleolipids were converted into their corresponding 2-cyanoethyl phosphoramidites 4b–9b. Figure 3

• pyrimidine β-D-ribonucleoside head groups 1–3 [18]. Chemical formulae 1–9 and lipo-oligonucleotide sequences 10–15. Energy-minimized 3D structures of the lipophilic nucleoside headgroups 4a–9a. All 3D structures were calculated using the program ChemBio3D Ultra v. 12.0 (number of iterations, 387 ± 147

Sequence-specific RNA cleavage by PNA conjugates of the metal-free artificial ribonuclease tris(2-aminobenzimidazole)

• Friederike Danneberg,
• Alice Ghidini,
• Plamena Dogandzhiyski,
• Elisabeth Kalden,
• Roger Strömberg and
• Michael W. Göbel

Beilstein J. Org. Chem. 2015, 11, 493–498, doi:10.3762/bjoc.11.55

• have only pyrimidine bases, while RNA 15 and 17 have mainly purine bases in the corresponding regions. If the tris(2-aminobenzimidazole) cleaver interacts with the purine bases (e.g., by stacking) it is not impossible that this could also be related to the apparent lower rate and lower selectivity in

• RNAs 15 or 17 under identical conditions (Supporting Information File 1). The relatively low site specificity, as discussed above, may be related to the pyrimidine rich sequence of RNA 16. To examine whether PNA conjugates 10–14 would form molecular aggregates with noncognate oligonucleotides, the

The reactions of 2-ethoxymethylidene-3-oxo esters and their analogues with 5-aminotetrazole as a way to novel azaheterocycles

• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess and
• Viktor I. Saloutin

Beilstein J. Org. Chem. 2015, 11, 385–391, doi:10.3762/bjoc.11.44

• substitution. The use of diethyl 2-ethoxymethylidenemalonate in this reaction resulted in ethyl 7-hydroxytetrazolo[1,5-a]pyrimidine-6-carboxylate, while ethyl 2-ethoxymethylidenecyanoacetate yielded 5-[2,6-diamino-3,5-bis(ethoxycarbonyl)pyridinium-1-yl]tetrazol-1-ide through an alternative pathway. Ethyl 2

• -benzoyl-3-ethoxyprop-2-enoate reacted with 5-aminotetrazole by two reaction routes to form ethyl 2-benzoyl-3-(1H-tetrazol-5-ylamino)prop-2-enoate and ethyl 7-(1-ethoxy-1,3-dioxo-3-phenylpropan-2-yl)-5-phenyl-4,7-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate. Keywords: 5-aminotetrazole; cyclisation

• medical practice [1]. The possibility to generate pyrimidine and azolopyrimidine systems based thereon, which exhibit a wide spectrum of biological activity due to structural similarity with nitrogenous bases, is of a special interest [2][3][4][5]. Interaction of non-fluorinated 2-ethoxymethylidene-3-oxo

C-5’-Triazolyl-2’-oxa-3’-aza-4’a-carbanucleosides: Synthesis and biological evaluation

• Roberto Romeo,
• Caterina Carnovale,
• Salvatore V. Giofrè,
• Maria A. Chiacchio,
• Adriana Garozzo,
• Emanuele Amata,
• Giovanni Romeo and
• Ugo Chiacchio

Beilstein J. Org. Chem. 2015, 11, 328–334, doi:10.3762/bjoc.11.38

• ][11][12]. Many structural variations of the natural nucleosides have been exploited. In general, the performed modifications included the replacement of the furanose moiety by other carbon or heterocyclic systems [13][14] or even acyclic fragments [15][16], the substitution of pyrimidine or purine

• –alkyne cycloadditions, no traces of 1,5-regioisomers were observed [47][48]. The structure of the obtained compounds was assessed according to 1H NMR, 13C NMR and MS data. In particular, the 1H NMR spectra of 5-methyl-1-[(3RS,5SR)-2-methyl-3-(1H-1,2,3-triazol-1-ylmethyl)isoxazolidin-5-yl]pyrimidine-2,4

• (1H,3H)diones 13 and 5-methyl-1-[(3RS,5RS)-2-methyl-3-(1H-1,2,3-triazol-1-ylmethyl)isoxazolidin-5-yl]pyrimidine-2,4(1H,3H)diones 14 show, besides the resonances of the protons of the isoxazolidine unit, diagnostic resonances at 7.25–7.75 ppm, as a singlet, for the proton of the triazole system, and at

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

• , arylethylenes, and arylacetylenes were used as precursors of the acyloxy fragment. The cross-dehydrogenative C–O coupling with 2-arylpyridines 4 proceeds also in the presence of the Cu(OAc)2/O2 system [40] and under electrochemical oxidation in the presence of Pd(II) salts [41]. The pyrimidine (acetoxylation of

• arenes (Scheme 4). The pyridine, pyrimidine, or pyrazole moiety serves as the directing group in the oxidative ortho-alkoxylation of arenes 16 with the Cu(OAc)2/AgOTf/O2 system giving coupling products 17 (Scheme 5) [47]. It is supposed that copper is inserted into the C–H bond of arene, the resulting Cu

NAA-modified DNA oligonucleotides with zwitterionic backbones: stereoselective synthesis of A–T phosphoramidite building blocks

• Boris Schmidtgall,
• Claudia Höbartner and
• Christian Ducho

Beilstein J. Org. Chem. 2015, 11, 50–60, doi:10.3762/bjoc.11.8

• phosphoramidites with X representing pyrimidine or purine nucleobases appears to be feasible. This will enable the preparation of NAA-modified oligonucleotides with significant variations in the base sequence. We are currently finishing the synthesis of a comprehensive set of corresponding X–T phosphoramidites

The unexpected influence of aryl substituents in N-aryl-3-oxobutanamides on the behavior of their multicomponent reactions with 5-amino-3-methylisoxazole and salicylaldehyde

• Volodymyr V. Tkachenko,
• Elena A. Muravyova,
• Sergey M. Desenko,
• Oleg V. Shishkin,
• Svetlana V. Shishkina,
• Dmytro O. Sysoiev,
• Thomas J. J. Müller and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2014, 10, 3019–3030, doi:10.3762/bjoc.10.320

• azoloazine with high chemo- and regioselectivity [11][13][14][15]. In particular, three-component heterocyclizations involving 3-amino-1,2,4-triazoles or 4-substituted 5-aminopyrazoles yielded either 4,5,6,7-tetrahydroazolo[1,5-a]pyrimidine-6-carboxamides under ultrasonication at room temperature (kinetic

• control) or 4,7-dihydroazolo[1,5-a]pyrimidine-6-carboxamides at reflux in an applicable solvent (thermodynamic control), respectively (Scheme 1). The behavior of the reaction of 5-aminopyrazoles containing substituents in the position 3 is influenced by the structure of aminoazoles and aldehydes, giving

• ). Obtaining of two classes of compounds was found to originate from steric influence rendered by the alkyl moiety of the ester group in the active methylene species. Inspired by Světlik’s studies, Jing et al. [17] developed an efficient method for the synthesis of oxygen-bridged pyrimidine tricyclic

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• (Table 2) show that the phenanthridine/phenanthridinium cation interacts with purine ss-sequences with affinity approximately one–two orders of magnitude lower in comparison to ds-DNA or ds-RNA, while interaction with pyrimidine ss-polynucleotides is even one order of magnitude lower. This agrees well

Synthesis of nanodiamond derivatives carrying amino functions and quantification by a modified Kaiser test

• Gerald Jarre,
• Steffen Heyer,
• Elisabeth Memmel,
• Thomas Meinhardt and
• Anke Krueger

Beilstein J. Org. Chem. 2014, 10, 2729–2737, doi:10.3762/bjoc.10.288

• ]pyrimidine derivatives. For the quantification of primary amino groups a modified photometric assay based on the Kaiser test has been developed and validated for different types of aminated nanodiamond. The results correspond well to values obtained by thermogravimetry. The method represents an alternative

• the IR spectrum (Figure 2), namely the vibrations at 1590, 1530 and 1430 cm−1 are caused by the grafted heteroaromatic moieties. The spectrum corresponds well to the signals observed for 2,4-bis(methylthio)pyrimidine [17]. The surface loading was determined by TGA and elemental analysis based on the

• the sulfones (see spectra c) and d) in Figure 2). A control experiment using nanodiamond not functionalized with the pyrimidine proved the reactivity of surface groups of the nanodiamond (CH, OH, π-bonds etc. are present on thermally annealed nanodiamond [18]) with MCPBA showing the formation of

Preparation of neuroprotective condensed 1,4-benzoxazepines by regio- and diastereoselective domino Knoevenagel–[1,5]-hydride shift cyclization reaction

• László Tóth,
• Yan Fu,
• Hai Yan Zhang,
• Attila Mándi,
• Katalin E. Kövér,
• Tünde-Zita Illyés,
• Attila Kiss-Szikszai,
• Balázs Balogh,
• Tibor Kurtán,
• Sándor Antus and
• Péter Mátyus

Beilstein J. Org. Chem. 2014, 10, 2594–2602, doi:10.3762/bjoc.10.272

• -1',2'-dihydro-2H,7b'H,9'H-spiro[pyrimidine-5,8'-quinolino[1,2-d][1,4]benzoxazepine]-2,4,6(1H,3H)-trione (rac-trans-7a): To a stirred solution of rac-5 (100 mg, 0.27 mmol) in chloroform (5 mL), anhydrous MgSO4 (150 mg, 1.25 mmol) and 1,3-dimethylbarbituric acid (60 mg, 0.38 mmol) were added and the

Versatile synthesis of amino acid functionalized nucleosides via a domino carboxamidation reaction

• Vicky Gheerardijn,
• Jos Van den Begin and
• Annemieke Madder

Beilstein J. Org. Chem. 2014, 10, 2566–2572, doi:10.3762/bjoc.10.268

• using palladium-based coupling chemistry to the pyrimidine C5 or the 7-position of 7-deaza-2’-deoxyadenosine [38][39][40]. During enzymatic incorporation the extra functionalities do not need to be protected. However, solid phase DNA synthesis implies an appropriate protection of the extra

• of imidazole modified pyrimidine and purine derivatives for solid phase synthesis have been described to date [41][44][45][46][47], we believe that the reactions described here serve as an ideal model system, which can be extended to other commercially available amino acid derivatives and nucleosides

• of the pyrimidine double bond, transfer hydrogenation with cyclohexene as hydrogen source and 10% palladium on carbon should be used [60][61][62]. As the methyl ester derivative of the amino acid is commercially available but rather expensive, we performed the esterification reaction on the benzyl

Pyrrolidine nucleotide analogs with a tunable conformation

• Lenka Poštová Slavětínská,
• Dominik Rejman and
• Radek Pohl

Beilstein J. Org. Chem. 2014, 10, 1967–1980, doi:10.3762/bjoc.10.205

• analogs [12]. In this publication, we present a conformational analysis of pyrrolidine azanucleotide analogs 7–14 containing thymine and adenine as examples of pyrimidine and purine nucleobases, respectively (Figure 2), and show how the conformation is affected by the mode of the phosphonate moiety

Syntheses of ¹⁵N-labeled pre-queuosine nucleobase derivatives

• Jasmin Levic and
• Ronald Micura

Beilstein J. Org. Chem. 2014, 10, 1914–1918, doi:10.3762/bjoc.10.199

• . Keywords: heterocycles; ligands; nucleic acids; nucleobases; nucleosides; pyrrolopyrimidinones; Introduction The small pyrrolo[2,3-d]pyrimidine 7-(aminomethyl)-7-deazaguanine is a natural product, also termed prequeuosine base (preQ1 base) [1][2]. This guanine derivative is involved in the complex

• chromatography on SiO2 and isolated in good yields. The pyrrolo[2,3-d]pyrimidine ring system of preQ1 base was built in good yields via the cyclocondensation reaction between [15N1,15N3,H215N(C2)]-2,6-diaminopyrimidin-4-one (6) and the 2-bromo-3-phthalimidopropan-1-al (7). Finally, deprotection was performed

• pyrrolo[2,3-d]pyrimidine ring system is based on the cyclocondensation reaction between α-bromoaldehydes and 2,6-diaminopyrimidin-4-ones and utilizes [15N]-KCN, [15N]-phthalimide, and [15N3]-guanidine for 15N sources to achieve three complementary labeling patterns that cover all five nitrogen atoms of

Synthesis of a bifunctional cytidine derivative and its conjugation to RNA for in vitro selection of a cytidine deaminase ribozyme

• Nico Rublack and
• Sabine Müller

Beilstein J. Org. Chem. 2014, 10, 1906–1913, doi:10.3762/bjoc.10.198

• ',3'-bis-O-(tert-butyldimethylsilyl)-1-[4-(N'-biotinyl-3,6-dioxaoctane-1,8-diamine)pyrimidine-2(1H)-onyl]-β-D-riboside (12). I: 2.6 equiv ZnBr2, DCM, 1 d, rt, Ar, 82%; II: 1.1 equiv EDAC·HCl, 1.1 equiv biotin, DMF, 0 °C → rt, overnight, 65%; III: THF/TFA/H2O (4:1:1, v/v/v), 0 °C, 5 h, 94%. Formation

Structure/affinity studies in the bicyclo-DNA series: Synthesis and properties of oligonucleotides containing bc^en-T and iso-tricyclo-T nucleosides

• Branislav Dugovic,
• Michael Wagner and
• Christian J. Leumann

Beilstein J. Org. Chem. 2014, 10, 1840–1847, doi:10.3762/bjoc.10.194

• oligonucleotides under the conditions of measurement. The corresponding Tm-data are summarized in Table 2. The bcen-T modification destabilizes duplexes with complementary DNA by −1.4 to −2.0 °C per modification relative to dT in a somewhat sequence dependent context. If flanked by two pyrimidine nucleotides (ON1

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• a secondary amine (i.e., dimethylamine [49][50], diethylamine [51][52], N-methylbenzylamine [49], pyrrolidine [53][54], or piperidine [55][56]) at temperatures ranging from 60 °C to 100 °C afforded the corresponding 5-(alkylaminomethyl)pyrimidine nucleosides 2 (Scheme 2). Compounds 2 served as

• rather limited. Zhang et al. obtained a series of pyrimidine nucleoside-thazolidinone hybrids 15 from 5-formyl-3',5'-di-O-acetyl-2'-deoxyuridine (14), an arylamine and mercaptoacetic acid (Scheme 6) [65]. The reactions were performed in a ionic liquid ([bmim]PF6). Products 15 were obtained in good to

The chemoenzymatic synthesis of clofarabine and related 2′-deoxyfluoroarabinosyl nucleosides: the electronic and stereochemical factors determining substrate recognition by E. coli nucleoside phosphorylases

• Ilja V. Fateev,
• Konstantin V. Antonov,
• Irina D. Konstantinova,
• Tatyana I. Muravyova,
• Frank Seela,
• Roman S. Esipov,
• Anatoly I. Miroshnikov and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2014, 10, 1657–1669, doi:10.3762/bjoc.10.173

• ; Introduction Pyrimidine and purine 2-deoxy-2-fluoro-β-D-arabinofuranosides demonstrate a broad spectrum of biological activity [1][2][3][4][5][6][7][8][9] and are valuable constituents of artificial oligonucleotides of great molecular biological and medicinal potential [10][11]. Among this family of

• obtained in 29 and 39% yield, respectively [19]. Previously, we have applied the MacDonald method for the synthesis of α-D-arabinofuranose-1-phosphate (Ara-1P) and showed that it is a versatile substrate for the enzymatic synthesis of both purine and pyrimidine nucleosides [22][23]. In addition, we

• pyrimidine β-D-arabinofuranosides by using α-D-arabinofuranose-1-phosphate (Ara-1P) as the glycosylating agent and the respective recombinant E. coli nucleoside phosphorylases as biocatalysts [22][23]. It was thus shown that Ara-1P is a universal glycosylating substrate for the synthesis of both purine and

Pyrene-modified PNAs: Stacking interactions and selective excimer emission in PNA₂DNA triplexes

• Alex Manicardi,
• Lucia Guidi,
• Alice Ghidini and
• Roberto Corradini

Beilstein J. Org. Chem. 2014, 10, 1495–1503, doi:10.3762/bjoc.10.154

• sequence with prevalence of pyrimidine bases, complementary to cystic fibrosis W1282X point mutation were synthesized. These compounds showed sequence-selective switch-on of pyrene excimer emission in the presence of target DNA, due to PNA2DNA triplex formation, with stability depending on the number and

• recognition; triplex stabilization; Introduction Peptide nucleic acid (PNA) probes are very selective in the recognition of DNA and have been used in a large variety of diagnostic methods, easily allowing the detection of point mutations at very low concentrations [1][2][3]. Poly-pyrimidine PNA can form very

• homopyrimidine sequences since the presence of one or more purine residues destabilizes these complexes and favour the formation of less stable duplexes [8]. Therefore it would be of great value to adopt strategies for the stabilization of triplex structures even in the presence of non-pyrimidine bases. From the

Stereoselective synthesis of carbocyclic analogues of the nucleoside Q precursor (PreQ₀)

• Sabin Llona-Minguez and
• Simon P. Mackay

Beilstein J. Org. Chem. 2014, 10, 1333–1338, doi:10.3762/bjoc.10.135

• ; stereoselective amine synthesis; triol synthesis; Introduction 7-Deazapurine (pyrrolo[2,3-d]pyrimidine) nucleosides are commonly found in nature playing a variety of roles such as building blocks of nucleic acids and tRNA, metabolites or antimetabolites [1]. Deazapurine ribonucleosides also show interesting

• , respectively [5][6]. In turn, the biosynthesis of PreQ0 originates from guanosine 5’-triphosphate (GTP, 4) [7] (Figure 1) and involves four steps via a tetrahydropterine intermediate. The pyrrolo[2,3-d]pyrimidine core is a privileged scaffold for the development of kinase inhibitors; an inspection of the

• to prepare diverse chiral amine building blocks and react them with a common halo-purine intermediate to obtain the desired final products. The pyrrolo[2,3-d]pyrimidine core of PreQ0 was furnished following a method described by Klepper et al. [13] (Figure 3). The two step process started with the

Synthesis, characterization and DNA interaction studies of new triptycene derivatives

• Sourav Chakraborty,
• Snehasish Mondal,
• Rina Kumari,
• Sourav Bhowmick,
• Prolay Das and
• Neeladri Das

Beilstein J. Org. Chem. 2014, 10, 1290–1298, doi:10.3762/bjoc.10.130

• generated when a purine (A/G) or a pyrimidine (C/T) base is stripped off from the DNA strand and this is considered as the most common type of DNA damage lesions. We generated one abasic site in a 48-base pair long oligomer duplex by treating the DNA (Figure 3) with Uracil DNA Glycosylase (UDG) enzyme

Use of activated enol ethers in the synthesis of pyrazoles: reactions with hydrazine and a study of pyrazole tautomerism

• Denisa Tarabová,
• Stanislava Šoralová,
• Martin Breza,
• Marek Fronc,
• Wolfgang Holzer and
• Viktor Milata

Beilstein J. Org. Chem. 2014, 10, 752–760, doi:10.3762/bjoc.10.70

• species, which are possible for ester compounds 5b and 5c are shown in Figure 3, with the last character of the label being an E indicates enol, O denotes oxo, and (Z,E) – HO vs OH/=O Compound 5b was previously prepared by a ring contraction of pyrimidine-2,4-dione [19]. It is known from the literature

• enol ether/hydrazine is 1:1, as in the case of the reaction with 3c, the formation of 7-aminopyrazolo[1,5-a]pyrimidine-3,6-dicarbonitrile could be expected as a byproduct [24][25]. When hydrazine hydrochloride is used [14], ethyl 3-ethoxypyrazole-4-carboxylate was obtained in 41% yield and the expected

The Flögel-three-component reaction with dicarboxylic acids – an approach to bis(β-alkoxy-β-ketoenamides) for the synthesis of complex pyridine and pyrimidine derivatives

• Mrinal K. Bera,
• Moisés Domínguez,
• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 394–404, doi:10.3762/bjoc.10.37

• dihydropyrimidinones or the corresponding dihydropyrimidinethiones. Due to their general importance (e.g. as biologically active compounds) the development of efficient protocols for the preparation of functionalized pyridine [10][11][12][13][14][15][16][17][18][19][20] and pyrimidine derivatives [21][22][23][24][25

• E- and Z-configured enamide moieties [51][52], finally leading to identical products. After these successful multicomponent reactions we investigated the intramolecular condensations of the bis(β-ketoenamides) 13–15 to pyridine and pyrimidine derivatives. Enamides 13 and 14 were treated with

• acetate in a sealed tube we obtained a 1:1 mixture of bis(pyrimidine) derivative 23a and pyrimidine 23b still containing one β-ketoenamide unit with an overall yield of 68%. However, full conversion of 13 into 23a was achieved by increasing the amount of ammonium acetate to 16 equiv and using a higher

Organobase-catalyzed three-component reactions for the synthesis of 4H-2-aminopyrans, condensed pyrans and polysubstituted benzenes

• Moustafa Sherief Moustafa,
• Saleh Mohammed Al-Mousawi,
• Maghraby Ali Selim,
• Ahmed Mohamed Mosallam and
• Mohamed Hilmy Elnagdi

Beilstein J. Org. Chem. 2014, 10, 141–149, doi:10.3762/bjoc.10.11

• the products. Finally, these compounds were used for the efficient synthesis of 6-amino-5-cyanonicotinic acid ester derivatives 31a,b, ethyl 4-amino-5H-pyrano[2,3-d]pyrimidine-6-carboxylates 33a,b, 4-amino-6H-pyrrolo[3,4-g]quinazoline-9-carbonitrile 39, and 1,7-diamino-6-(N'-hydroxycarbamimidoyl)-3

• acid derivatives 31a,b, ethyl 4-amino-5H-pyrano[2,3-d]pyrimidine-6-carboxylates 33a,b, 4-amino-6H-pyrrolo[3,4-g]quinazoline-9-carbonitrile 39, and 1,7-diamino-6-(N'-hydroxycarbamimidoyl)-3-oxo-5-phenyl-3H-isoindole-4-carboxylate 40. X-ray crystal structure of 9. X-ray crystal structure of 13a. X-ray

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

IBD-mediated oxidative cyclization of pyrimidinylhydrazones and concurrent Dimroth rearrangement: Synthesis of [1,2,4]triazolo[1,5-c]pyrimidine derivatives

• Caifei Tang,
• Zhiming Li and
• Quanrui Wang

Beilstein J. Org. Chem. 2013, 9, 2629–2634, doi:10.3762/bjoc.9.298

• Caifei Tang Zhiming Li Quanrui Wang Department of Chemistry, Fudan University, 200433 Shanghai, P. R. of China 10.3762/bjoc.9.298 Abstract Oxidative cyclization of 6-chloro-4-pyrimidinylhydrazones 4 with iodobenzene diacetate (IBD) in dichloromethane gives rise to [1,2,4]triazolo[4,3-c]pyrimidine

• pyrimidine moiety is an important pharmacophore [1]. Especially, the fused bi- or tricyclic heterocyles containing a pyrimidine motif have received considerable interest in the design and discovery of new compounds for pharmaceutical and herbicidal applications [2][3]. For example, the pyrrolo[2,3-d

• ]pyrimidine derivative, ruxolitinib (INCB018424), was discovered as a selective JAK1 and JAK2 inhibitor, which is currently under clinical investigation [4]. To date, a number of fused pyrimidine-type compounds have been successfully commercialized, such as the pyrazolo[3,4-d]pyrimidine allopurinol and the