- 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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- Oxidative Annulations Involving DMSO and Formamide: K2S2O8 Mediated Syntheses of Quinolines and Pyrimidines
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An efficient strategy toward 4-arylquinolines and 4-arylpyrimidines from readily available precursors is described. Oxidative annulation promoted by K2S2O8 involving anilines, aryl ketones, and DMSO as a methine (=CH-) equivalent leads to 4-arylquinolines via a cascade that entails generation of a sulfenium ion, subsequent C-N and C-C bond formations, and cyclization. The application of this strategy to the activation of acetophenone-formamide conjugates toward the synthesis of 4-arylpyrimidines is also described.
- Jadhav, Santosh D.,Singh, Anand
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supporting information
p. 5673 - 5676
(2017/10/25)
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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 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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- Fast and green one-pot multicomponent synthesis of a library of pyrrolo[1,2-c] pyrimidines under microwave irradiation
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A simple, clean and rapid one-pot three component, microwave-assisted synthesis of pyrrolo[1,2-c]pyrimidine derivatives starting from various substituted pyrimidines, 2-bromoacetophenones and nonsymmetrical, electron deficient alkynes in 1,2-epoxybutane which acts both as solvent and acid scavenger is reported. This one-pot three component synthesis implies short reaction times being at the same time highly cost-effective and environmental friendly.
- Georgescu, Emilian,Georgescu, Florentina,Draghici, Constantin,Cristian, Liliana,Popa, Marcel Mirel,Dumitrascu, Florea
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p. 851 - 857
(2014/03/21)
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- Design, synthesis, and structure-activity relationships of novel 6,7-disubstituted-4-phenoxyquinoline derivatives as potential antitumor agents
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Two series of quinoline derivatives bearing the pyridine/pyrimidine scaffold were synthesized, and evaluated for their c-Met kinase inhibitory activity and antiproliferative activity against 5 cancer cell lines (HT-29, H460, MKN-45, A549, and U87MG) were evaluated in vitro. Most compounds showed moderate to excellent potency, and compared to foretinib, the most promising analog 18b (c-Met half-maximal inhibitory concentration [IC50] = 1.39 nM) showed a 7.3-fold increase in activity against HT-29 cell line in vitro. Structure-activity relationship studies indicated that regulation of the electron density on the pyridine/pyrimidine ring to a proper degree was a key factor in improving the antitumor activity.
- Tang, Qidong,Zhao, Yanfang,Du, Xinming,Chong, Lian'E,Gong, Ping,Guo, Chun
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