A novel approach to oxoisoaporphine alkaloids via regioselective metalation of alkoxy isoquinolines

• Benedikt C. Melzer and
• Franz Bracher

Beilstein J. Org. Chem. 2017, 13, 1564–1571, doi:10.3762/bjoc.13.156

• from 1-iodoisoquinolines 8a–c. Synthesis of the alkaloids 6-O-demethylmenisporphine (4), dauriporphinoline (5), and bianfugecine (6). Attempted synthesis of bianfugecine (6) via directed remote metalation and subsequent trapping of the carboxamide group. Outcome of a D2O quenching experiment after

New tricks of well-known aminoazoles in isocyanide-based multicomponent reactions and antibacterial activity of the compounds synthesized

• Maryna V. Murlykina,
• Maryna N. Kornet,
• Sergey M. Desenko,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Aleksander A. Brazhko,
• Vladimir I. Musatov,
• Erik V. Van der Eycken and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2017, 13, 1050–1063, doi:10.3762/bjoc.13.104

• -binucleophile, acid – catalyst). Literature data indicate [14][25][59][97][98][99][100][101] that 5-aminopyrazoles bearing in the fourth position electron-withdrawing substituents like carboxamide, carboxylate or a carbonitrile group, posses chemical properties being different from other 5-aminopyrazoles but

• sometimes similar to 3-amino-1,2,4-triazole that was described as a component of GBB-3CR earlier [71][72][73][74][75]. Therefore, the first type of aminoazoles studied in our work was 5-amino-N-aryl-1H-pyrazole-4-carboxamide that showed 1,3-binucleophile properties in the condensation with aromatic

• -pyrazole-4-carboxamide (2b), methyl benzaldehyde-4-carboxylate (1f) and tert-butylisocyanide (3a, Table 2). Obviously, this reaction requires a longer reaction time (min. 48 h) and a moderate temperature (not more than 85 °C) to avoid tarring. Thus, after 48 h of heating (oil bath) at 85 °C the starting

Regioselective (thio)carbamoylation of 2,7-di-tert-butylpyrene at the 1-position with iso(thio)cyanates

• Anna Wrona-Piotrowicz,
• Marzena Witalewska,
• Janusz Zakrzewski and
• Anna Makal

Beilstein J. Org. Chem. 2017, 13, 1032–1038, doi:10.3762/bjoc.13.102

• evaporated. The products were isolated by flash chromatography (eluent: CH2Cl2). 2,7-Di-tert-butyl-N-ethylpyrene-1-carboxamide (3a). White solid (293 mg, 76%). Mp 258–259 °C; 1H NMR (600 MHz, CDCl3) δ 8.26 (s, 1H), 8.20 (d, J = 1.8 Hz, 1H), 8.18 (d, J = 1.8 Hz, 1H), 8.03 (m, 3H), 7.98 (d, J = 9.0 Hz, 1H

Synthesis of ribavirin 2’-Me-C-nucleoside analogues

• Fanny Cosson,
• Aline Faroux,
• Jean-Pierre Baltaze,
• Jonathan Farjon,
• Régis Guillot,
• Jacques Uziel and
• Nadège Lubin-Germain

Beilstein J. Org. Chem. 2017, 13, 755–761, doi:10.3762/bjoc.13.74

• catalytic hydrogenolysis. The latter reaction simultaneously cleaves the benzyl and isopropylidene groups affording compound 2 as a single isomer [22]. In the case of 5-(2’-deoxy-2’-methyl-2’-fluoro-β-D-ribosyl)-1,2,3-triazole-4-carboxamide (3) the synthesis was more delicate as it is necessary to

• procedures for compounds 2, 5–7, and 10–18 are covered by the Ph.D. thesis of Fanny Cosson [22]. 5-(2’-C-Methyl-β-D-ribofuranosyl)-1,2,3-triazole-4-carboxamide (2) [22]: Through the solution of compound 7 (mixture of 7a and 7b, 0.49 g, 1.1 mmol) in anhydrous methanol (14 mL) was bubbled ammonia gas for 2 h

• at 0 °C. Then the mixture was stirred for 12 h at rt and concentrated in vacuum. The residue was purified by flash chromatography (EtOAc/cyclohexane, 3:7 to 1:0) affording the mixture of the corresponding 1-benzyl-4-(2’,3’-O-isopropylidene-2’-C-methyl-β-D-ribofuranosyl)-1,2,3-triazole-5-carboxamide

Characterization of the synthetic cannabinoid MDMB-CHMCZCA

• Carina Weber,
• Stefan Pusch,
• Dieter Schollmeyer,
• Sascha Münster-Müller,
• Michael Pütz and
• Till Opatz

Beilstein J. Org. Chem. 2016, 12, 2808–2815, doi:10.3762/bjoc.12.279

• legislation in 17 of the 30 member states of the EMCDDA [8]. It contains an N-alkylated indole core structure with carboxamide substituent in C-3 position, linked to an tert-leucine methyl ester and in previous studies, the amino acid was shown to be S-configurated [9]. Lately, the new synthetic cannabinoid

Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction

• Salvatore V. Giofrè,
• Santa Cirmi,
• Raffaella Mancuso,
• Francesco Nicolò,
• Giuseppe Lanza,
• Laura Legnani,
• Agata Campisi,
• Maria A. Chiacchio,
• Michele Navarra,
• Bartolo Gabriele and
• Roberto Romeo

Beilstein J. Org. Chem. 2016, 12, 2793–2807, doi:10.3762/bjoc.12.278

• ]-4'-carboxamide (6e): Yellow oil (Yield: 52 mg, 38%); IR (neat) νmax: 1705, 1686, 1628 cm−1; 1H NMR (500 MHz, CDCl3) δ 7.71–7.67 (m, 1H), 7.62–7.26 (m, 8H), 4.17 (d, J = 12.7 Hz, 1H), 4.10–4.03 (m, 1H), 3.99 (d, J = 12.7 Hz, 1H), 3.88–3.79 (m, 1H), 3.74–3.66 (m, 1H), 3.62–3.54 (m, 1H), 3.54–3.40 (m

Enzymatic synthesis and phosphorolysis of 4(2)-thioxo- and 6(5)-azapyrimidine nucleosides by E. coli nucleoside phosphorylases

• Vladimir A. Stepchenko,
• Anatoly I. Miroshnikov,
• Frank Seela and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2016, 12, 2588–2601, doi:10.3762/bjoc.12.254

• ) and the role of some amino acid residues of the catalytic site was characterized by the single-site mutagenesis [41]. It was suggested that the uracil binding site includes Gln166, the carboxamide group of which forms two strong hydrogen bonds 3N(H)···(O=)C(R)-NH2···(O=)C-2. Moreover, the carbonyl

Diastereoselective synthesis of 3,4-dihydro-2H-pyran-4-carboxamides through an unusual regiospecific quasi-hydrolysis of a cyano group

• Mikhail Yu. Ievlev,
• Oleg V. Ershov,
• Mikhail Yu. Belikov,
• Angelina G. Milovidova,
• Viktor A. Tafeenko and
• Oleg E. Nasakin

Beilstein J. Org. Chem. 2016, 12, 2093–2098, doi:10.3762/bjoc.12.198

• TCNE and ketones) with aldehydes in an acidic media. An unusual process of quasi hydrolysis of the cyano group was observed in the course of the described regio- and diastereoselective transformation. Keywords: diastereoselectivity; 3,4-dihydro-2H-pyran-4-carboxamide; nitriles; pyran; quasi-hydrolysis

• been recently described is the involvement of diazolactones in an inverse electron-demand Diels–Alder reaction [13]. At the same time the synthesis of 3,4-dihydro-2H-pyrans with a carboxamide group is a not sufficiently explored area. There is only one way to produce 3,4-dihydro-2H-pyran-4-carboxamides

• diastereoselective cascade reaction [23]. The crucial stage of the described transformation is the formation of a pyran-4-carboxamide intermediate. A trace amount of it was isolated accidentally and we could not repeat this procedure and characterize the compound by spectra. Results and Discussion In continuation of

A flow reactor setup for photochemistry of biphasic gas/liquid reactions

• Josef Schachtner,
• Patrick Bayer and
• Axel Jacobi von Wangelin

Beilstein J. Org. Chem. 2016, 12, 1798–1811, doi:10.3762/bjoc.12.170

• convenience, reductive work-up with triphenylphosphine (PPh3) was performed to obtain the stable allyl alcohol derivative 3a which offers ample opportunities for chemical manipulations at the alcohol, alkene, and carboxamide functions. The choice of solvent is crucial as it determines the solubility of the

Synthesis of pyrrolo[2,1-f][1,2,4]triazin-4(3H)-ones: Rearrangement of pyrrolo[1,2-d][1,3,4]oxadiazines and regioselective intramolecular cyclization of 1,2-biscarbamoyl-substituted 1H-pyrroles

• Kkonnip Son and
• Seong Jun Park

Beilstein J. Org. Chem. 2016, 12, 1780–1787, doi:10.3762/bjoc.12.168

• of 3-chloro-1H-pyrrole-2-carboxylic acid (13) using the Vilsmeier reagent [9], followed by further amination to produce 1H-pyrrole-2-carboxamide 14 in good to excellent yield [9]. A reaction mixture of 14 with NaOH, NH4Cl, and NaClO led to the formation of the N-aminopyrrole 15 [11]. The addition of

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• as well as amino and carboxamide nucleophiles in lieu of a hydroxy group in 132 were accepted, yielding δ-lactam and glutarimide moieties, respectively [131][132]. When the B-domain of the rhiPKS was exchanged with an X-domain of glutarimide-producing PKS from the 9-methylstreptimidone PKS of S

Application of Cu(I)-catalyzed azide–alkyne cycloaddition for the design and synthesis of sequence specific probes targeting double-stranded DNA

• Svetlana V. Vasilyeva,
• Vyacheslav V. Filichev and
• Alexandre S. Boutorine

Beilstein J. Org. Chem. 2016, 12, 1348–1360, doi:10.3762/bjoc.12.128

• -aminobutyric acid, Py – N-methylpyrrole carboxamide and Dp – N,N-dimethylaminopropylamine residues) was synthesized in the laboratory by solid-phase method [36][37] and used as a polyamide component. The first model is interesting for an anti-HIV strategy, but it is not suitable for visualization of dsDNA

Enantioselective carbenoid insertion into C(sp³)–H bonds

• J. V. Santiago and
• A. H. L. Machado

Beilstein J. Org. Chem. 2016, 12, 882–902, doi:10.3762/bjoc.12.87

• ) carboxamide complexes (R)-18 and (S)-18, the configuration of the new stereogenic center of 20f was reversed, probably due to the lack of the oxygen atom in the substituent R, as suggested by the authors. In 1997, Davies and Hansen reported the intermolecular carbenoid insertion into C(sp3)–H catalyzed by

• reagents, also used as solvent, were cyclopentane, cyclohexane and cycloheptane. Two factors are noteworthy in this work. Unlike the carboxamide complexes (R)-18 and (S)-18 previously reported by Doyle and coworkers (Table 2), where the complexation of the chiral ligand to rhodium atoms occurs through the

• carboxamide group, in the new chiral catalyst (S)-23 the rhodium atoms are complexed to the chiral ligands by the carboxylate group, similar to those chiral complexes presented by Ikegami and coworkers (Table 1). Another important feature of this work is, unlike to the work that preceded it, that the new

New synthetic strategies for xanthene-dye-appended cyclodextrins

• Milo Malanga,
• Andras Darcsi,
• Mihaly Balint,
• Gabor Benkovics,
• Tamas Sohajda and
• Szabolcs Beni

Beilstein J. Org. Chem. 2016, 12, 537–548, doi:10.3762/bjoc.12.53

• of the compound (Supporting Information File 1, Figure S27). In the 2D spectrum shown in Supporting Information File 1, Figure S27, the cross peak between the carbon of the carboxamide at around 174 ppm and the proton of the methylene moiety of the glucose unit that bears the fluorophore (C6sub) at

Friedel–Crafts-type reaction of pyrene with diethyl 1-(isothiocyanato)alkylphosphonates. Efficient synthesis of highly fluorescent diethyl 1-(pyrene-1-carboxamido)alkylphosphonates and 1-(pyrene-1-carboxamido)methylphosphonic acid

• Anna Wrona-Piotrowicz,
• Janusz Zakrzewski,
• Anna Gajda,
• Tadeusz Gajda,
• Anna Makal,
• Arnaud Brosseau and
• Rémi Métivier

Beilstein J. Org. Chem. 2015, 11, 2451–2458, doi:10.3762/bjoc.11.266

• approximately two-fold increase in solution fluorescence quantum yield in comparison with that of a model N-alkyl pyrene-1-carboxamide. This effect was tentatively explained by stiffening of the amidophosphonate lateral chain which was caused by the interaction (intramolecular hydrogen bond) of phosphonate and

• photodecomposition in this solvent [32], we found that this did not happen in the case of the compounds investigated here). Electronic absorption and emission spectra of 3a in various solvents are shown in Figure 2. The introduction of a phosphonato group into the N-alkyl chain of the pyrene carboxamide fluorophore

The marine sponge Agelas citrina as a source of the new pyrrole–imidazole alkaloids citrinamines A–D and N-methylagelongine

• Christine Cychon,
• Ellen Lichte and
• Matthias Köck

Beilstein J. Org. Chem. 2015, 11, 2029–2037, doi:10.3762/bjoc.11.220

• . The structure of 1 is very similar to mauritiamine (7) [12] and its 2´-debromo derivative nagelamide P (18) [13]. The 1D and 2D 1H and 13C NMR spectra of 1 showed two additional signals for sp2 methines indicating two 3-bromopyrrole carboxamide moieties (Table 1). The similarities of the NMR data of 1

Development of variously functionalized nitrile oxides

• Haruyasu Asahara,
• Keita Arikiyo and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2015, 11, 1241–1245, doi:10.3762/bjoc.11.138

• , amides, aldehyde, and ketone upon treatment with hydroxide, alkoxide, amine, diisobutylaluminium hydride and Grignard reagent, respectively. In these transformations, N-methyl-N-tosylcarboxamides behave like a Weinreb amide. Similarly, N-methyl-5-phenylisoxazole-3-carboxamide was converted into 3

• aromatic and aliphatic amides, and a similar conversion of N-methyl-5-phenylisoxazole-3-carboxamide (3), which is equal to the generation of variously functionalized nitrile oxides. Results and Discussion At the outset, methanesulfonylation (mesylation) of amides was studied. To a suspension of N,4

• alcohol 11j were also detected (Table 2, entries 18 and 19). In contrast to tosylated amides 8Ab and 8Bb, tosylated N-methyl-5-phenylisoxazole-3-carboxamide 12 exhibited higher reactivity. Upon tosylation under similar conditions 3 did not afford product 12, and isoxazole-3-carboxylic acid 5a, a

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

• hydroxyaryl group as well as tricyclic nitrogen-containing heterocycles derived from salicylaldehyde have been reported as anticancer [1], antihypertensive agents [2], neuropeptide Y antagonists [3], and calcium channel blockers [4]. Fused azoloazines containing carboxamide substituents also exhibit a broad

• 48 h the reaction proceeded to form mainly two compounds – Knoevenagel adduct 7 and Schiff base 8 (Scheme 3). Trace amounts of 2-hydroxy-N-(2-methoxyphenyl)-2-methyl-4-(3-methylisoxazol-5-ylamino)chroman-3-carboxamide (4a) were detected in the reaction mixture as well. Furthermore, both conventional

• alia, ultrasonic activation was applied to promote this multicomponent reaction. It was established that the three-component cyclocondensation of the starting compounds under ultrasonication at room temperature for 4 h led to the selective formation of the substituted chroman-3-carboxamide 4a in 58

Synthesis and characterization of a new photoinduced switchable β-cyclodextrin dimer

• Florian Hamon,
• Claire Blaszkiewicz,
• Marie Buchotte,
• Estelle Banaszak-Léonard,
• Hervé Bricout,
• Sébastien Tilloy,
• Eric Monflier,
• Christine Cézard,
• Laurent Bouteiller,
• Christophe Len and
• Florence Djedaini-Pilard

Beilstein J. Org. Chem. 2014, 10, 2874–2885, doi:10.3762/bjoc.10.304

• ’-Bis[6I-deoxy-β-cyclodextrin-6I-yl]carboxamide-4,4’-azobenzene, AZO-CDim (1): β-CD-NH2 (2.02 g, 1.78 mmol, 2 equiv) and 3 (404 mg, 0.87 mmol, 1 equiv) were dissolved in 5 mL of dried distilled DMF. After 16 h of stirring at room temperature, the mixture was concentrated and the product precipitated by

Asymmetric Ugi 3CR on isatin-derived ketimine: synthesis of chiral 3,3-disubstituted 3-aminooxindole derivatives

• Giordano Lesma,
• Fiorella Meneghetti,
• Alessandro Sacchetti,
• Mattia Stucchi and
• Alessandra Silvani

Beilstein J. Org. Chem. 2014, 10, 1383–1389, doi:10.3762/bjoc.10.141

• amine and the isonitrile-derived primary carboxamide functional groups (Scheme 1). Also, this chemical correlation of the major diastereoisomer 10a allowed us to further confirm the prevailing S-configuration at the tetrasubstituted stereocenter C3 of the Ugi products. Compound 15a was submitted to a

Integration of enabling methods for the automated flow preparation of piperazine-2-carboxamide

• Richard J. Ingham,
• Claudio Battilocchio,
• Joel M. Hawkins and
• Steven V. Ley

Beilstein J. Org. Chem. 2014, 10, 641–652, doi:10.3762/bjoc.10.56

• Abstract Here we describe the use of a new open-source software package and a Raspberry Pi® computer for the simultaneous control of multiple flow chemistry devices and its application to a machine-assisted, multi-step flow preparation of pyrazine-2-carboxamide – a component of Rifater®, used in the

• treatment of tuberculosis – and its reduced derivative piperazine-2-carboxamide. Keywords: automation; flow chemistry; hydration; hydrogenation; sustainable processing; Introduction Enabling synthesis technologies such as flow chemistry are becoming commonplace in modern laboratories (for recent reviews

• database for medicinal chemistry. For example, piperazine-2-carboxamide (1, Figure 2a) is an amino acid derivative with interesting biological properties [17]. At the time of writing, racemic 1 was identified as a notably expensive building block [18] and thus a good target for this transformation. We have

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

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

• . 2'-(4-tert-Butyl-5-methoxy-6-methylpyrimidin-2-yl)-N-(4-methoxy-2,2-dimethyl-5-oxohex-3-en-3-yl)biphenyl-2-carboxamide (24b): IR (ATR) ν: 3325 (N-H), 3065–2865 (=C-H, C-H), 1700, 1665 (C=O), 1550–1445 (C=C) cm−1; 1H NMR (CDCl3, 500 MHz) δ 0.71 (s, 9H, t-Bu), 1.26 (s, 9H, t-Bu), 2.31, 2.33 (2 s, 3H

An efficient method for the construction of polysubstituted 4-pyridones via self-condensation of β-keto amides mediated by P₂O₅ and catalyzed by zinc bromide

• Liquan Tan,
• Peng Zhou,
• Cui Chen and
• Weibing Liu

Beilstein J. Org. Chem. 2013, 9, 2681–2687, doi:10.3762/bjoc.9.304

• -diphenylpyridine-3-carboxamide (2a) in 94% GC yield (Table 1, entries 2, 4–6). Results of the screening study of the amount of ZnBr2 and P2O5 (Table 1, entries 6–8 and 12) indicated that 0.2 equiv of ZnBr2 and 1.5 equiv of P2O5 was sufficient for the completion of this transformation. In order to improve the

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265