The first example of the Fischer–Hepp type rearrangement in pyrimidines

• Inga Cikotiene,
• Mantas Jonusis and
• Virginija Jakubkiene

Beilstein J. Org. Chem. 2013, 9, 1819–1825, doi:10.3762/bjoc.9.212

• -pyrimidinediamines. It was found that the outcome of the reaction strongly depends on the structure of the pyrimidines. Activation of the pyrimidine ring by three groups with a positive mesomeric effect is crucial for the intramolecular nitroso group migration. Keywords: Fischer–Hepp rearrangement; nitrosation; 5

• -nitrosopyrimidines; nucleophilic substitution; pyrimidinediamines; Introduction The pyrimidine moiety is an important structural motif in natural products and therefore frequently used as a building block for pharmaceutical agents [1][2]. It is well-known that chemical properties of pyrimidines depend on the π

• rebuttal to the article about the electrophilic nitrosation of selected pyrimidines [15]. We showed that instead of the previously reported electrophilic attack of the C-5 by NO+, the secondary amino substituents in position 4 of the pyrimidine ring underwent N-nitrosation reactions (Scheme 2). We also

3-Pyridylnitrene, 2- and 4-pyrimidinylcarbenes, 3-quinolylnitrenes, and 4-quinazolinylcarbenes. Interconversion, ring expansion to diazacycloheptatetraenes, ring opening to nitrile ylides, and ring contraction to cyanopyrroles and cyanoindoles

• Curt Wentrup,
• Nguyen Mong Lan,
• Adelheid Lukosch,
• Pawel Bednarek and
• David Kvaskoff

Beilstein J. Org. Chem. 2013, 9, 743–753, doi:10.3762/bjoc.9.84

• 21 → 20, with free energies of activation of 18–22 kcal/mol in solution, has been demonstrated for 1,2,3-triazolo[1,5-a]pyrimidines [24] but not for 1,2,3-triazolo[1,5-c]pyrimidines [25][26]. However, 7-benzyl-3-ethoxycarbonyl-1,2,3-triazolo[1,5-c]pyrimidin-5-ol and its diazo valence tautomer, 6-(2

• -diazoethoxycarbonylmethylene)-2-(α-hydroxybenzyl)pyrimidin-4-(2H)-one, have been reported [27]. We find that FVT of the 4- and 2-(5-tetrazolyl)pyrimidines 22–24 also affords cyanopyrroles (Scheme 8). FVT of 2-(5-tetrazolyl)pyrimidine (22) affords a ca. 1:1 ratio of 2- and 3-cyanopyrroles (Scheme 8). The results of FVT of

Some aspects of radical chemistry in the assembly of complex molecular architectures

• Béatrice Quiclet-Sire and
• Samir Z. Zard

Beilstein J. Org. Chem. 2013, 9, 557–576, doi:10.3762/bjoc.9.61

• . Synthesis of bicyclic cyclobutane motifs. Construction of the CD rings of steroids. Rapid assembly of polyquinanes. Formation of a polycyclic structure via an allene intermediate. A polycyclic structure via the alkylative Birch reduction. Synthesis of polycyclic pyrimidines and indoline structures

Diarylethene-modified nucleotides for switching optical properties in DNA

• Sebastian Barrois and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2012, 8, 905–914, doi:10.3762/bjoc.8.103

• reactivity the 5-position of pyrimidines (U/T and C) and the 8-position of purines (A and G) are preferred as chromophore modification sites. The assumption, that these points of attachment allow the chromophores to point into the major groove is only partially true, if at all. In particular, large and

• base pairing. In the case of the pyrimidines the modification at position 5 should not significantly interfere with the preferred anti-conformation of the nucleosidic bond. Thus, the Watson–Crick base pairing of the corresponding modified oligonucleotides should be maintained. Over the past few years

Synthesis and characterization of Sant-75 derivatives as Hedgehog-pathway inhibitors

• Chao Che,
• Song Li,
• Bo Yang,
• Shengchang Xin,
• Zhixiong Yu,
• Taofeng Shao,
• Chuanye Tao,
• Shuo Lin and
• Zhen Yang

Beilstein J. Org. Chem. 2012, 8, 841–849, doi:10.3762/bjoc.8.94

• heterocycles (motif C) and the position of the nitrogen atom in pyridine. As shown in Scheme 6, para-substituted pyridine was first replaced with meta- and ortho-pyridine, and other heterocycles, including pyrimidines and five-membered heteroaryl rings, as well as nonaromatic heterocycles, such as morpholine

Chemistry of polyhalogenated nitrobutadienes, 10: Synthesis of highly functionalized heterocycles with a rigid 6-amino-3-azabicyclo[3.1.0]hexane moiety

• Viktor A. Zapol’skii,
• Jan C. Namyslo,
• Armin de Meijere and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2012, 8, 621–628, doi:10.3762/bjoc.8.69

• substitution. Therefore, upon treatment with the azabicyclohexane 1 under mild conditions (methanol, rt) the enamine 24 was formed in 86% yield (Scheme 6). Similar pyrido[1,2-a]pyrimidines show antiviral [29], antithrombotic [30] and antibacterial [31][32][33][34] activities. Alternatively, conversion of bis

Synthesis, solid-state fluorescence properties, and computational analysis of novel 2-aminobenzo[4,5]thieno[3,2-d]pyrimidine 5,5-dioxides

• Kenichirou Yokota,
• Masayori Hagimori,
• Naoko Mizuyama,
• Yasuhisa Nishimura,
• Hiroshi Fujito,
• Yasuhiro Shigemitsu and
• Yoshinori Tominaga

Beilstein J. Org. Chem. 2012, 8, 266–274, doi:10.3762/bjoc.8.28

• the π–π-electron conjugated system in the sulfonyl group of benzothienopyrimidine 5,5-dioxide is stronger than that of the carbonyl group of the indeno pyrimidines. Benzo[4,5]thieno[3,2-d]pyrimidine derivative 6 and benzo[4,5]furo[3,2-d]pyrimidine derivative 7 showed different emission properties from

Regioselectivity in the multicomponent reaction of 5-aminopyrazoles, cyclic 1,3-diketones and dimethylformamide dimethylacetal under controlled microwave heating

• Kamal Usef Sadek,
• Ramadan Ahmed Mekheimer,
• Tahany Mahmoud Mohamed,
• Moustafa Sherief Moustafa and
• Mohamed Hilmy Elnagdi

Beilstein J. Org. Chem. 2012, 8, 18–24, doi:10.3762/bjoc.8.3

• pyrazoloquinolinones (Hantzsch-type dihydropyridines). On the other hand, the use of sonication at room temperature under neutral conditions favours the formation of isomeric pyrazolo[5,1-b]quinazolin-8(4H)-ones (Biginelli-type dihydro-pyrimidines) [9]. Employing more nucleophilic bases to catalyse the reaction

Synthesis of diverse dihydropyrimidine-related scaffolds by fluorous benzaldehyde-based Biginelli reaction and post-condensation modifications

• Bruno Piqani and
• Wei Zhang

Beilstein J. Org. Chem. 2011, 7, 1294–1298, doi:10.3762/bjoc.7.150

• with four boronic acids yielded 5-biaryl-5H-thiazolo[3,2-a]pyrimidines 6a–h in 55–64% yields after F-SPE and flash chromatography purifications (Table 2). Dihydropyrimidinethione 4f was used for the Liebeskind–Srogl coupling reaction with a phenylboronic acid to convert to 2-aryl-1,6-dihydropyrimidine

Functionalization of heterocyclic compounds using polyfunctional magnesium and zinc reagents

• Paul Knochel,
• Matthias A. Schade,
• Sebastian Bernhardt,
• Georg Manolikakes,
• Albrecht Metzger,
• Fabian M. Piller,
• Christoph J. Rohbogner and
• Marc Mosrin

Beilstein J. Org. Chem. 2011, 7, 1261–1277, doi:10.3762/bjoc.7.147

• pyrimidines and purines are very important for the design of antiviral agents. The amination of this class of heterocycles is of particular importance. Recently, we developed an oxidative amination procedure for lithium derivatives using chloranil as oxidation agent [43]. We applied this procedure in the

• using TMPMgCl·LiCl (41) or TMP2Mg·2LiCl (129) The directed magnesiation of aromatic substrates using TMPMgCl·LiCl (41) constitutes an economical preparation of a range of functionalized arylmagnesium compounds [25][26]. Sensitive heterocycles such as pyrimidines can be readily magnesiated with

Synthesis, reactivity and biological activity of 5-alkoxymethyluracil analogues

• Lucie Brulikova and
• Jan Hlavac

Beilstein J. Org. Chem. 2011, 7, 678–698, doi:10.3762/bjoc.7.80

• efficient synthetic route for the preparation of ethoxy-substituted 5-(perfluoroalkyl)pyrimidines (Scheme 10) and investigated their regioselective transformations [18]. Some of these fluorine-containing pyrimidine analogues are potent antitumor and antiviral agents. The reported synthesis started with the

• treatment of 5-bromo-2,4-diethoxypyrimidine (65) with either perfluorobutyl or perfluorohexyl iodide in the presence of activated copper bronze in DMSO. This reaction afforded 5-(perfluoroalkyl)pyrimidines 66 and 67 in high yields. Subsequent acid hydrolysis of 66 and 67 provided 5-(perfluoroalkyl

• )pyrimidines 68 and 69. The latter readily underwent nucleophilic attack by alkoxide ions to yield alicyclic or cyclic acetals 70–73 and 74, respectively, depending on the alcohol used. Uridine and arabinofuranosyl analogues: 5-Substituted uracil nucleosides where the sugar component is ribose or arabinose

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

C–C (alkynylation) vs C–O (ether) bond formation under Pd/C–Cu catalysis: synthesis and pharmacological evaluation of 4-alkynylthieno[2,3-d]pyrimidines

• Dhilli Rao Gorja,
• K. Shiva Kumar,
• K. Mukkanti and
• Manojit Pal

Beilstein J. Org. Chem. 2011, 7, 338–345, doi:10.3762/bjoc.7.44

• /C–CuI–PPh3 catalytic system facilitated C–C bond formation between 4-chlorothieno[2,3-d]pyrimidines and terminal alkynes in methanol with high selectivity without generating any significant side products arising from C–O bond formation between the chloro compounds and methanol. A variety of novel 4

• -alkynylthieno[2,3- d]pyrimidines were prepared via alkynylation of 4-chlorothieno[2,3-d]pyrimidines in good to excellent yields. Some of the compounds synthesized were tested for cytotoxic activity in vitro. Keywords: catalysis; C–C bond; copper; palladium; thieno[2,3-d]pyrimidine; Introduction Alkynyl

• substituted pyrimidines are of considerable pharmacological interest because of their notable biological activities [1], in particular, adenosine kinase inhibitory activity in the treatment of pain and inflammatory diseases [2] and thymidylate synthase inhibitory properties in cancer therapy [3]. On the other

Approaches towards the synthesis of 5-aminopyrazoles

• Ranjana Aggarwal,
• Vinod Kumar,
• Rajiv Kumar and
• Shiv P. Singh

Beilstein J. Org. Chem. 2011, 7, 179–197, doi:10.3762/bjoc.7.25

• -dielectrophiles has been extensively used for the preparation of bicyclic nitrogen heterocycles, especially in the preparation of condensed heterocycles such as pyrazolo[3,4-d]pyrimidines, pyrazolo[3,4-b]pyridines, imidazopyrazoles etc. In view of significant interest in the synthesis of these heterocyclics, we

Synthesis of some novel hydrazono acyclic nucleoside analogues

• Mohammad N. Soltani Rad,
• Ali Khalafi-Nezhad and
• Somayeh Behrouz

Beilstein J. Org. Chem. 2010, 6, No. 49, doi:10.3762/bjoc.6.49

• ], hereby, we wish to report the synthesis of some novel hydrazono acyclic nucleosides having similar scaffolds to the miconazole framework. In these compounds, the nucleobases including pyrimidines, purines and other azole derivatives were substituted as heterocyclic cores and the ether bond in miconazole

• . This proved to be the case, and the corresponding ketones 1h–1o could not be obtained satisfactorily by this method. The main limitation of using the aforementioned pathway for purines and pyrimidines is their low solubility in acetonitrile, which results in low yields of the corresponding ketones 1h

Synthesis of some novel annulated pyrido[2,3-d]pyrimidines via stereoselective intramolecular hetero Diels–Alder reactions of 1-oxa-1,3-butadienes

• Mohit L. Deb and
• Pulak J. Bhuyan

Beilstein J. Org. Chem. 2010, 6, No. 11, doi:10.3762/bjoc.6.11

• Mohit L. Deb Pulak J. Bhuyan Medicinal Chemistry Division, North East Institute of Science & Technology, Jorhat 785006, Assam, India, Fax: 0376 2370011 10.3762/bjoc.6.11 Abstract Some novel annulated pyrido[2,3-d]pyrimidines 6 and 7 were synthesized stereoselectively by intramolecular hetero

• Diels–Alder reactions involving 1-oxa-1,3-butadienes. Keywords: β-halo aldehydes; hetero Diels–Alder reaction; 1-oxa-1,3-butadiene; pyrido[2,3-d]pyrimidines; uracil; Introduction The importance of uracil and its annulated derivatives is well recognized by synthetic as well as biological chemists [1][2

• ][3][4][5][6][7][8]. Pyrido[2,3-d]pyrimidines represent a broad class of annelated uracils which have received considerable attention over the past years due to their wide range of biological activities such as antibacterial [9][10], antitumor [11][12], cardiotonic [13][14], hepatoprotective [13

Synthesis of 2-substituted 9-oxa-guanines {5-aminooxazolo[5,4-d]pyrimidin- 7(6H)-ones} and 9-oxa-2-thio- xanthines {5-mercaptooxazolo[5,4-d]pyrimidin- 7(6H)-ones}

• Subrata Mandal,
• Wen Tai Li,
• Yan Bai,
• Jon D. Robertus and
• Sean M. Kerwin

Beilstein J. Org. Chem. 2008, 4, No. 26, doi:10.3762/bjoc.4.26

• Subrata Mandal Wen Tai Li Yan Bai Jon D. Robertus Sean M. Kerwin College of Pharmacy, 1 University Station, University of Texas, Austin, TX, 78712, USA Department of Biochemistry,1 University Station, University of Texas, Austin, TX, 78712, USA 10.3762/bjoc.4.26 Abstract Oxazolo[5,4-d]pyrimidines

• preparation of a series of 2-substituted 5-aminooxazolo[5,4-d]pyrimidin-7(6H)-ones and related 5-thio-oxazolo[5,4-d]pyrimidines is described, including analogs suitable for further elaboration employing “click” chemistry utilizing copper-catalyzed Huisgen 1,3-dipolar cycloadditions. Two of the compounds

• prepared were found to inhibit ricin with IC50 ca. 1–3 mM. Keywords: Annulation; Click Chemistry; Cyclization; Purine Analogs; Ricin; Introduction Oxazolo[5,4-d]pyrimidines have been reported to possess a variety of biological activities including kinase inhibition [1][2], adenosine receptor antagonism

Perhalogenated pyrimidine scaffolds. Reactions of 5-chloro- 2,4,6-trifluoropyrimidine with nitrogen centred nucleophiles

• Emma L. Parks,
• Graham Sandford,
• John A. Christopher and
• David D. Miller

Beilstein J. Org. Chem. 2008, 4, No. 22, doi:10.3762/bjoc.4.22

• desirable process but one of the most difficult to achieve in practice. Pyrimidines are electron-deficient aromatic systems and, when halogenated, become very useful substrates for a variety of nucleophilic aromatic substitution (SNAr) processes [9] and, since numerous chloropyrimidines are commercially

The tert- amino effect in heterocyclic chemistry: Synthesis of new fused pyrazolinoquinolizine and 1,4-oxazinopyrazoline derivatives

• Dipak Prajapati and
• Kalyan Jyoti Borah

Beilstein J. Org. Chem. 2007, 3, No. 43, doi:10.1186/1860-5397-3-43

• undergoing a 1,5-(4 → 5) hydride shift prior to cyclization to yield a 6-membered ring product 6 (Scheme 2). This is in contrast to an earlier report by Sandhu et al to obtain pyrrolo [2,3-d]pyrimidines from 6-tert-amino-substituted uracils and dimethyl acetylenedicarboxylate.[32] However, further work is in

An easy synthesis of 5-functionally substituted ethyl 4-amino- 1-aryl- pyrazolo- 3-carboxylates: interesting precursors to sildenafil analogues

• Said A. S. Ghozlan,
• Khadija O. Badahdah and
• Ismail A. Abdelhamid

Beilstein J. Org. Chem. 2007, 3, No. 15, doi:10.1186/1860-5397-3-15

• report results of our work aimed at exploring this synthetic methodology and adoption of products for the synthesis of pyrazolo[4.3-d]pyrimidines. Thus, compounds 1a-c, were prepared according to literature procedures via coupling of ethyl cyanoacetate with aromatic diazonium salts [10]. It has been

The Elbs and Boyland- Sims peroxydisulfate oxidations

• E. J. Behrman

Beilstein J. Org. Chem. 2006, 2, No. 22, doi:10.1186/1860-5397-2-22

• Intermediate with the Hydroxide Ion. A Catalytic Cycle for Peroxydisulfate Consumption. A Non-catalytic cycle for Peroxydisulfate Consumption. Oxidation of phenols Oxidation of anilines Oxidation of coumarins Oxidation of xanthones Oxidation of flavones Oxidation of pyridines Oxidation of pyrimidines Oxidation

Microwave- assisted ring closure reactions: Synthesis of 8-substituted xanthine derivatives and related pyrimido- and diazepinopurinediones

• Joachim C. Burbiel,
• Jörg Hockemeyer and
• Christa E. Müller

Beilstein J. Org. Chem. 2006, 2, No. 20, doi:10.1186/1860-5397-2-20

• derivatives by refluxing in HMDS, while the analogous ring closure reactions of imidazo [1,2-c]pyrimidines (e.g. 14) to the corresponding imidazo [1,2,3-cd]purine derivatives, and of pyrimido [1,6-a][1,3]diazepines (e.g. 16) to the diazepino [1,2,3-cd]purine derivatives failed under these conditions (Table 1

An efficient synthesis of novel pyrano[2,3-d]- and furopyrano[2,3-d]pyrimidines via indium- catalyzed multi- component domino reaction

• Dipak Prajapati and
• Mukut Gohain

Beilstein J. Org. Chem. 2006, 2, No. 11, doi:10.1186/1860-5397-2-11

• Dipak Prajapati Mukut Gohain Department of Medicinal Chemistry, Regional Research Laboratory, Jorhat 785006, Assam, India 10.1186/1860-5397-2-11 Abstract Various novel pyrano [2,3-d]pyrimidines 5 and furopyrano [2,3-d]pyrimidines 7 were synthesized in 80–99% yields via a multicomponent domino

• , [19][20][21] most of which rely on multi-step reactions with yields being low. [22][23] The furo [2,3-d]pyrimidine derivatives act as useful sedatives, antihistamines, diuretics, muscle relaxants and antiulcer agents. Furthermore, pyrano [2,3-d]pyrimidines also represent broad classes of annelated

• ], we have investigated a new, simple and efficient synthesis of novel fused pyrimidines based on inverse electron-demand Diels-Alder reaction using ethyl vinyl ether/dihydrofuran and α,β-ethylenic ketones formed in situ as heterodienes in presence of 1 mol% of indium(III) trichloride (Scheme 1). This

One-pot synthesis of novel 1H-pyrimido[4,5-c][1,2]diazepines and pyrazolo[3,4-d]pyrimidines

• Dipak Prajapati,
• Partha P. Baruah,
• Baikuntha J. Gogoi and
• Jagir S. Sandhu

Beilstein J. Org. Chem. 2006, 2, No. 5, doi:10.1186/1860-5397-2-5

• ]diazepines 3 & 4 and pyrazolo [3,4-d]pyrimidines 6 were regioselectively synthesised by the reaction of 1,3-dimethyl-6-hydrazinouracils 1 with various α,β-unsaturated compounds 2 and α-ketoalkynes 8 in excellent yields. Introduction The importance of uracil and its annelated substrates is well recognized by

• heteroannulation of uracils usually require either forcing conditions[16][17] or relatively longer synthetic pathways.[18] Also, pyrazolo [3,4-d]pyrimidines are a class of naturally occurring fused uracils that possess a wide range of biological activity.[19] Allopurinol (6-dehydroxy-pyrazolo [3,4-d]pyrimidine

• -unsaturated compounds and α-ketoalkynes, which give access to an efficient unprecedented one-pot synthesis of novel pyrimido [4,5-c][1,2]diazepine-6,8-diones 3 or 4 and pyrazolo [3,4-d]pyrimidines 6 in excellent yields. A previous synthesis of pyrimido [4,5-c][1,2]diazepines reported by Mallory et al.[25