- Mechanistic aspect of ring transformations in the reaction of 5-nitro-4-pyrimidinone with acetophenone derivatives and cycloalkanones depending on the electron density/ring size of the ketone
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3-Methyl-5-nitro-4-pyrimidinone undergoes two kinds of nucleophilic type ring transformations upon treatment with cycloalkanones in the presence of ammonium acetate, which affords 4,5-disubstituted pyrimidines and 5,6-disubstituted 3-nitro-2-pyridones. In order to improve the synthetic utility of this reaction, it is necessary to control the regioselectivity of these ring transformations. In the present work, we performed DFT calculation to realize the selectivity of two ring transformation products. In cases of adduct intermediates derived from cyclohexanone and cyclooctanone, the 2-attack proceeds preferably to give condensed pyrimidines. On the other hand, the adduct intermediate derived from cycloheptanone undergoes the 4-attack predominantly to afford condensed nitropyridone.
- Nishiwaki, Nagatoshi,Sugimoto, Ryuichi,Saigo, Kazuhiko,Kobiro, Kazuya
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- Catalyst free synthesis of mono- and disubstituted pyrimidines from O-acyl oximes
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Transition-metal or iodine catalyzed transformations of O-acyl oximes to various N-heterocycles are well established. Herein, we report a catalyst free, oxime carboxylate based, three-component condensation method to access mono- and disubstituted pyrimidines. A broad range of substituted pyrimidines were prepared in moderate to excellent yields. Control experiments reveal that in situ generated formamidine is the key intermediate.
- Upare, Atul,Sathyanarayana, Pochampalli,Kore, Ranjith,Sharma, Komal,Bathula, Surendar Reddy
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p. 2430 - 2433
(2018/05/23)
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- Pd-catalyzed decarboxylative cross-coupling of sodium pyrimidinecarboxylates with (hetero)aryl bromides
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A straightforward method for the synthesis of functionalized 4- or 5-(hetero)arylpyrimidines via decarboxylative cross-coupling reaction from readily available pyrimidine-4- and pyrimidine-5-carboxylates was described. In the presence of dual-catalyst system of Pd(PPh3)4/Cu2O, the reaction proceeds smoothly, tolerates a variety of functional groups, and provides easy access to the synthesis of different (hetero)arylpyrimidines compounds.
- Wang, Shengqiang,Lu, Hongtao,Zou, Dapeng,Wu, Yangjie,Li, Jingya,Wu, Yusheng,Zou, Dapeng,Wu, Yusheng,Li, Jingya
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supporting information
p. 2723 - 2726
(2017/06/23)
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- Synthesis, and docking studies of phenylpyrimidine-carboxamide derivatives bearing 1H-pyrrolo[2,3-b]pyridine moiety as c-Met inhibitors
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Four series of phenylpyrimidine-carboxamide derivatives bearing 1H-pyrrolo[2,3-b]pyridine moiety (14a-e, 15a-g, 16a-e and 17a-g) were designed, synthesized and evaluated for the IC50 values against three cancer cell lines (A549, PC-3 and MCF-7). Four selected compounds (15e, 16a-b and 17a) were further evaluated for the activity against c-Met kinase, HepG2 and Hela cell lines. Most of the compounds showed excellent cytotoxicity activity and selectivity with the IC50 valuables in single-digit μM to nanomole range. Eleven of them are equal to more active than positive control Foretinib against one or more cell lines. The most promising compound 15e showed superior activity to Foretinib against A549, PC-3 and MCF-7 cell lines, with the IC50 values of 0.14 ± 0.08 μM, 0.24 ± 0.07 μM and 0.02 ± 0.01 μM, which were 4.6, 1.6 and 473.5 times more active than Foretinib (0.64 ± 0.26 μM, 0.39 ± 0.11 μM, 9.47 ± 0.22 μM), respectively. Structure-activity relationships (SARs) and docking studies indicated that the replacement of phenylpicolinamide scaffold with phenylpyrimidine fragment of the target compounds was benefit for the activity. What's more, the introduction of fluoro atom to the aminophenoxy part played no significant impact on the activity and any substituent group on aryl group is unfavourable for the activity.
- Zhu, Wufu,Wang, Wenhui,Xu, Shan,Wang, Jianqiang,Tang, Qidong,Wu, Chunjiang,Zhao, Yanfang,Zheng, Pengwu
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p. 1749 - 1756
(2016/04/05)
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- Synthesis, activity and docking studies of phenylpyrimidine–carboxamide Sorafenib derivatives
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Two series of Sorafenib derivatives bearing phenylpyrimidine–carboxamide moiety (16a–g and 17a–p) were designed, synthesized and evaluated for the IC50values against three cancer cell lines (A549, MCF-7 and PC-3). Two selected compounds (17f and 17n) were further evaluated for the activity against VEGFR2/KDR kinase. More than half of the synthesized compounds showed moderate to excellent activity against three cancer cell lines. Compound 17f showed equal activity to Sorafenib against MCF-7 cell line, with the IC50values of 6.35 ± 0.43 μM. Meanwhile, compound 17n revealed more active than Sorafenib against A549 cell line, with the IC50values of 3.39 ± 0.37 μM. Structure–activity relationships (SARs) and docking studies indicated that the second series (17a–p) showed more active than the first series (16a–g). What's more, the introduction of fluoro atom to the phenoxy part played no significant impact on activity. In addition, the presence of electron-donating on aryl group was benefit for the activity.
- Wang, Wenhui,Wu, Chunjiang,Wang, Jianqiang,Luo, Rong,Wang, Caolin,Liu, Xiaobo,Li, Jiqing,Zhu, Wufu,Zheng, Pengwu
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p. 6166 - 6173
(2016/12/06)
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- Direct access to pyrimidines through organocatalytic inverse-electron-demand Diels-Alder reaction of ketones with 1,3,5-triazine
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An organocatalytic inverse-electron-demand Diels-Alder reaction of ketones with 1,3,5-triazine through enamine catalysis has been developed. This method could furnish 4,5-disubstituted pyrimidines in good yields and high levels of regioselectivities.
- Yang, Gongming,Jia, Qianfa,Chen, Lei,Du, Zhiyun,Wang, Jian
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p. 76759 - 76763
(2015/09/28)
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- One-pot and three-component synthesis of substituted pyrimidines catalysed by boron sulfuric acid under solvent-free conditions
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An efficient, simple and one-pot synthesis of pyrimidine derivatives by a three-component reaction of ketones, triethyl orthoformate, and ammonium acetate in the presence of boron sulfuric acid as a reusable and efficient catalyst under solvent-free conditions is reported. The reusability of catalyst, simplicity of the starting materials, short reaction time, one-pot, and good yields of products are the main advantages.
- Soheilizad, Mehdi,Adiba, Mehdi,Sajjadifarb, Sami
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p. 524 - 527
(2014/12/10)
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- One-pot synthesis of pyrimidines under solvent-free conditions
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N,N,N',N'-Tetrabromobenzene-1,3-disulfonamide was used as an efficient catalyst for the one-pot synthesis of pyrimidine derivatives in excellent yields from triethoxymethane, ammonium acetate, and various ketone derivatives at 100-110 °C under solvent-fre
- Ghorbani-Vaghei, Ramin,Karimi-Nami, Rahman,Toghraei-Semiromi, Zahra,Amiri, Mostafa,Salimi, Zahra,Ghavidel, Mehdi
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p. 324 - 330
(2014/04/17)
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- Copper catalyzed ipso-nitration of iodoarenes, bromoarenes and heterocyclic haloarenes under ligand-free conditions
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A catalytic protocol for the conversion of haloarenes into the corresponding nitroarenes is presented using copper salts under ligand-free conditions. The method was effectively utilized for the ipso-nitration of a broad variety of haloarenes that includes iodoarenes, bromoarenes, and heterocyclic haloarenes.
- Amal Joseph,Priyadarshini,Lakshmi Kantam,Maheswaran
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supporting information; experimental part
p. 1511 - 1513
(2012/03/27)
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- One-step synthesis of 4,5-disubstituted pyrimidines using commercially available and inexpensive reagents
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4,5-Disubstituted pyrimidines are synthesized from the corresponding ketone in one-step using inexpensive reagents (formamidine acetate, n-propanol, heat). Contrasted to other methods, this process appears quite amenable to large-scale use in industrial settings.
- Baran, Phil S.,Shenvi, Ryan A.,Nguyen, Steven A.
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p. 581 - 586
(2008/02/02)
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- Novel synthesis of bihetaryl compounds
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The ring transformation of nitropyrimidinone 1 with acetophenone derivatives 2 affords two kinds of azaheterocyclic compounds, 4-phenylpyrimidines 3 and 3-nitro-6-phenyl-2-pyridones 4. On the basis of the relationship between electronic properties of the substituent and ratios of products, a plausible reaction mechanism is provided. Furthermore, the present reaction could be applied to heterocyclic ketones giving bihetaryl compounds.
- Nishiwaki, Nagatoshi,Yamashita, Keiko,Azuma, Mayumi,Adachi, Tomoko,Tamura, Mina,Ariga, Masahiro
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p. 1996 - 2000
(2007/10/03)
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- NOVEL SYNTHESIS OF SUBSTITUTED PYRIMIDINES: A RING TRANSFORMATION OF 3-METHYL-5-NITROPYRIMIDIN-4(3H)-ONE
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A novel ring transformation of 3-methyl-5-nitropyrimidin-4(3H)-one with ketones in the presence of ammonia was found to be an elegant method for synthesizing 5,6-disubstituted pyrimidines.Tetrahydroquinazoline was readily obtained in good yields when cyclohexanone was employed as a substrate.The present reaction was applicable to cyclopentanone, acetophenone and p-nitroacetophenone to give corresponding pyrimidine derivatives.
- Nishiwaki, Nagatoshi,Matsunaga, Tomoko,Thoda, Yasuo,Ariga, Masahiro
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p. 249 - 252
(2007/10/02)
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