First synthesis of acylated nitrocyclopropanes

• Kento Iwai,
• Rikiya Kamidate,
• Khimiya Wada,
• Haruyasu Asahara and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2023, 19, 892–900, doi:10.3762/bjoc.19.67

• reaction with dinucleophiles such as 2-aminopyridines, which affords pyrido[1,2-a]pyrimidinones through ring opening (Scheme 1, reaction a) [1]. Chemical transformations that take advantage of polyfunctionality are also possible. A six-membered ring forms between the aryl group and ester functionality

Synthesis and HDAC inhibitory activity of pyrimidine-based hydroxamic acids

• Virginija Jakubkiene,
• Gabrielius Ernis Valiulis,
• Markus Schweipert,
• Asta Zubriene,
• Daumantas Matulis,
• Franz-Josef Meyer-Almes and
• Sigitas Tumkevicius

Beilstein J. Org. Chem. 2022, 18, 837–844, doi:10.3762/bjoc.18.84

• ][28][29][30]. In this work, the pyrimidine-based hydroxamic acids were synthesized by aminolysis of the corresponding esters. The required esters 3 and 4 were obtained by alkylation of pyrimidinones 1 and 2 with ethyl 2-bromoethanoate in triethylamine in the presence of tetrabutylammonium bromide at

• methylene bridge linking the pyrimidine ring and the hydroxamic acid residue on the HDAC activity, hydroxamic acids 25–31 were synthesized (Scheme 2). In contrast to the synthesis of esters 3 and 4, alkylation of pyrimidinones 1 and 19 with the corresponding bromoesters in triethylamine in the presence of

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• , analgesic, etc. They form a major structural constituent of biomolecules like DNA and significant drugs like fluorouracil (65), zidovudine (66), lamivudine (67), risperidone (68), and buspirone (69, Figure 6) [65]. The biological importance of pyrimidinones like anticonvulsant (70), antiviral (71) and

• anticancer activities (72, Figure 6) [66][67][68][69] prompted chemists to develop newer methodologies for the synthesis of pyrimidinones with atom economy and high yields. The Biginelli reaction is one of the frequently employed MCRs for the synthesis of dihydropyrimidinones. The classical Biginelli

• -catalyzed three-component reaction between aromatic aldehydes 5, ethyl cyanoacetate (73) (active methylene group) and benzamidine (74) in aqueous media for the construction of substituted pyrimidinones 75 under microwave irradiation (Scheme 26). The study of the protocol on a conventional system directed a

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• fused at positions 16 and 17. In a recent report, Baji et al. [42] utilized a modified Biginelli-3CR between ketosteroid 41, urea and different benzaldehyde derivatives for the synthesis of steroid ring A-fused pyrimidinones 42. In this case, the heterocyclic ring was produced by a second step using the

Synthesis of pyrazolopyrimidinones using a “one-pot” approach under microwave irradiation

• Mark Kelada,
• John M. D. Walsh,
• Robert W. Devine,
• Patrick McArdle and
• John C. Stephens

Beilstein J. Org. Chem. 2018, 14, 1222–1228, doi:10.3762/bjoc.14.104

• the microwave-assisted synthesis of substituted pyrazolo[1,5-a]pyrimidinones, a core scaffold in many bioactive and pharmaceutically relevant compounds, has been established. A variety of substituents was tolerated at the 2 and 5 positions, including functionalized aryls, heterocycles, and alkyl

• the pyrazolo[1,5-a]pyrimidinones, that employ one-pot syntheses and/or processes have been encouraged and have become a major focus for many synthetic chemists [11]. As such, a convenient and general method of preparing the scaffold would be of significant interest to the pharmaceutical industry

• . Herein, we report such a strategy for the simple synthesis of functionalized pyrazolo[1,5-a]pyrimidinones that employs a one-pot microwave-assisted approach. Findings A number of synthetic approaches have been developed for the synthesis of privileged nitrogen-fused bicyclic systems such as the pyrazolo

Continuous-flow retro-Diels–Alder reaction: an efficient method for the preparation of pyrimidinone derivatives

• Imane Nekkaa,
• Márta Palkó,
• István M. Mándity and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2018, 14, 318–324, doi:10.3762/bjoc.14.20

• syntheses of various pyrimidinones as potentially bioactive products by means of the highly controlled continuous-flow retro-Diels–Alder reaction of condensed pyrimidinone derivatives are presented. Noteworthy, the use of this approach allowed us to rapidly screen a selection of conditions and quickly

• confirm the viability of preparing the desired pyrimidinones in short reaction times. Yields typically higher than those published earlier using conventional batch or microwave processes were achieved. Keywords: continuous-flow; desulfurisation; norbornene-fused heterocycles; pyrimidinones; retro-Diels

• the developed CF technology is superior to existing conventional batch technologies. Results and Discussion The starting materials, i.e., fused tricyclic or tetracyclic pyrimidinones 1–8 have been previously prepared by literature methods [26][45][46][47][48][49][50]. Cyclization of the corresponding

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• good oxidant for this reaction and allowed to carry out the trifluoromethylation exclusively at the α-position of the carbonyl group in the pyranone ring. The substrate scope was large and included 17 coumarins, 2 quinolines and 3 pyrimidinones. With coumarins bearing electron-donating groups on the

• give intermediate radical 65, which was oxidised by Mn(OAc)3 to form the carbocation 66 and, after deprotonation, the trifluoromethyl compounds (Scheme 39) [62]. The same group also reported a straightforward method for the trifluoromethylation of pyrimidinones and pyridinones under the same reaction

• conditions. 5-Trifluoromethylpyrimidinones and 3-trifluoromethylpyridinones were selectively obtained in moderate to good yields (Scheme 40). It was observed that the substituent R1 provided no stabilisation for the radical intermediate, so the less bulky substituents at 6-position of pyrimidinones or 4

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• . Magnesium iodide-catalyzed synthesis of quinazolines. Ferrous chloride-catalyzed aerobic dehydrogenation of 1,2,3,4-tetrahydroquinolines. Cu(I)-catalyzed oxidative aromatization of indoles. Putative mechanism of the transformation. Oxidative dehydrogenation of pyrimidinones and pyrimidines. Putative

Regiochemistry of cyclocondensation reactions in the synthesis of polyazaheterocycles

• Patrick T. Campos,
• Leticia V. Rodrigues,
• Andrei L. Belladona,
• Caroline R. Bender,
• Juliana S. Bitencurt,
• Fernanda A. Rosa,
• Davi F. Back,
• Helio G. Bonacorso,
• Nilo Zanatta,
• Clarissa P. Frizzo and
• Marcos A. P. Martins

Beilstein J. Org. Chem. 2017, 13, 257–266, doi:10.3762/bjoc.13.29

• in the ring junction represents the cyclocondensation reaction [4]. Pyrido[1,2-a]pyrimidinones [5], thiazolo[3,2-a]pyrimidinones [6], and pyrimido[1,2-a]benzimidazole [7] are examples of polyazaheterocycles obtained through the reaction of 1,3-dielectrophiles and 1,3-dinucleophiles. Appropriately

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• -deficient isocyanates resulted in lower yields. We then turned our attention to the pivotal intramolecular allylic substitution reaction of 19 to access syn- and anti-pyrimidinones 23 and 24. As previously reported [31], this diastereodivergent coupling could indeed be realized as shown in Scheme 4. Based

• [56][57], and the resulting aldehydes (not shown) were reduced to the terminal alcohols with NaBH4, giving the desired pyrimidinones 3 and 4. These compounds represent key intermediates which may be transformed into the targeted natural products 1 and 2 following previously established protocols [6

• precursor 5. Divergent Tsuji–Trost coupling and completion of the synthesis of authentic pyrimidinones 3 and 4. Supporting Information Supporting Information File 132: Full experimental details, characterization data of all products, copies of 1H and 13C NMR spectra and X-ray crystallographic data for 28