An Efficient Synthesis of 2‐Chloropyrimidines via Pd‐catalyzed Regioselective Dechlorination of 2,4‐Dichloropyrimidines in the Presence of NaHCO<sub>3</sub>

Zhang, Yangming; Gu, Min; Ma, Hui; Tang, Jie; Lü, Wei

doi:10.1002/cjoc.200890176

Cited by 10 publications

(7 citation statements)

References 15 publications

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“…For example, Pd-catalyzed dechlorination of AU2 proceeded to afford 3a in 61% yield. 30 Introduction of ethyl acetoacetate to AU2 in an SNAr manner followed by decarboxylation and deacetoxylation furnished a methylated compound 3b in low yield. 31 Hydroxylation of AU2 proceeded to afford 3c in 78% yield.…”

Section: Resultsmentioning

confidence: 99%

Discovery of 2,6-Dihalopurines as Stomata Opening Inhibitors: Implication of an LRX-mediated H+-ATPase Phosphorylation Pathway

Itami

Ueda

Aihara

et al. 2022

Preprint

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Stomata are pores in the leaf epidermis of plants and their opening and closing regulate gas exchange and water transpiration. Stomatal movements play key roles in both plant growth and stress responses. In recent years, small molecules regulating stomatal movements have been used as a powerful tool in mechanistic studies, as well as key players for agricultural applications. Therefore, the development of new molecules regulating stomatal movement and the elucidation of their mechanisms have attracted much attention. We herein describe the discovery of 2,6-dihalopurines, AUs, as a new stomatal opening inhibitor, and their mechanistic study. Based on biological assays, AUs may involve in the pathway related with plasma membrane H+-ATPase phosphorylation. In addition, we identified leucine-rich repeat extensin proteins (LRXs), LRX3, LRX4 and LRX5 as well as RALF, as target protein candidates of AUs by affinity based pull down assay and molecular dynamics simulation. The mechanism of stomatal movement related with the LRXs–RALF is an unexplored pathway, and therefore further studies may lead to the discovery of new signaling pathways and regulatory factors in the stomatal movement.

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Section: Resultsmentioning

confidence: 99%

Discovery of 2,6-Dihalopurines as Stomata Opening Inhibitors: Implication of an LRX-mediated H+-ATPase Phosphorylation Pathway

Itami

Ueda

Aihara

et al. 2022

Preprint

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“…Regioselective palladium-catalyzed hydrogenolysis of 38 in the presence of Na 2 CO 3 occurred exclusively at the C-4 position [75], and substitution of the remaining C-2 chloride with methoxide provided 40 in 79% yield over the two steps. Electrophilic bromination of 40 using bromine in acetic acid gave the desired C-7 bromo compound 41 .…”

Section: Resultsmentioning

confidence: 99%

“…Starting with commercially available methyl 3-aminothiophene-2-carboxylate, formation of the pyrimidine moiety using potassium cyanate and chlorination with POCl 3 provided dichloride 38 [ 74 ]. Regioselective palladium-catalyzed hydrogenolysis of 38 in the presence of Na 2 CO 3 occurred exclusively at the C-4 position [ 75 ], and substitution of the remaining C-2 chloride with methoxide provided 40 in 79% yield over the two steps. Electrophilic bromination of 40 using bromine in acetic acid gave the desired C-7 bromo compound 41 .…”

Section: Resultsmentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of PKD Inhibitors

et al. 2011

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Protein kinase D (PKD) belongs to a family of serine/threonine kinases that play an important role in basic cellular processes and are implicated in the pathogenesis of several diseases. Progress in our understanding of the biological functions of PKD has been limited due to the lack of a PKD-specific inhibitor. The benzoxoloazepinolone CID755673 was recently reported as the first potent and kinase-selective inhibitor for this enzyme. For structure-activity analysis purposes, a series of analogs was prepared and their in vitro inhibitory potency evaluated.

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“…Starting with commercially available methyl 3-aminothiophene-2-carboxylate, formation of the pyrimidine moiety using potassium cyanate, followed by chlorination with POCl 3 gave dichloride 15. 35 Palladium-catalyzed regioselective dechlorination of 15 in the presence of Na 2 CO 3 occurred exclusively at the C-4 position, 36 and substitution of the remaining C-2 chloride with methoxide provided 17 in 79% yield over the two steps. Electrophilic bromination of 17 using bromine in AcOH 37 gave the desired C-7 brominated compound 18.…”

Section: T H Imentioning

confidence: 99%

Synthesis and Structure−Activity Relationships of Benzothienothiazepinone Inhibitors of Protein Kinase D

Bravo‐Altamirano¹,

George²,

Frantz³

et al. 2010

ACS Med. Chem. Lett.

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Protein kinase D (PKD) is a member of a novel family of serine/threonine kinases that regulate fundamental cellular processes. PKD is implicated in the pathogenesis of several diseases, including cancer. Progress in understanding the biological functions and therapeutic potential of PKD has been hampered by the lack of specific inhibitors. The benzoxoloazepinolone CID755673 was recently identified as the first potent and selective PKD inhibitor. The study of structure-activity relationships (SAR) of this lead structure led to further improvements in PKD1 potency. We describe herein the synthesis and biological evaluation of novel benzothienothiazepinone analogs. We achieved a ten-fold increase in the in vitro PKD1 inhibitory potency for the second generation lead kb-NB142-70 and accomplished a transition to an almost equally potent novel pyrimidine scaffold, while maintaining excellent target selectivity. These promising results will guide the design of pharmacological tools to dissect PKD function and pave the way for the development of potential anti-cancer agents.

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An Efficient Synthesis of 2‐Chloropyrimidines via Pd‐catalyzed Regioselective Dechlorination of 2,4‐Dichloropyrimidines in the Presence of NaHCO₃

Abstract: An efficient synthesis of 2‐chloropyrimidines from readily accessible 2,4‐dichloropyrimidines was achieved via Pd‐catalyzed regioselective dechlorination in the presence NaHCO3.

Cited by 10 publications

References 15 publications

Discovery of 2,6-Dihalopurines as Stomata Opening Inhibitors: Implication of an LRX-mediated H+-ATPase Phosphorylation Pathway

Discovery of 2,6-Dihalopurines as Stomata Opening Inhibitors: Implication of an LRX-mediated H+-ATPase Phosphorylation Pathway

Design, Synthesis, and Biological Evaluation of PKD Inhibitors

Synthesis and Structure−Activity Relationships of Benzothienothiazepinone Inhibitors of Protein Kinase D

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An Efficient Synthesis of 2‐Chloropyrimidines via Pd‐catalyzed Regioselective Dechlorination of 2,4‐Dichloropyrimidines in the Presence of NaHCO3

Abstract: An efficient synthesis of 2‐chloropyrimidines from readily accessible 2,4‐dichloropyrimidines was achieved via Pd‐catalyzed regioselective dechlorination in the presence NaHCO3.

Cited by 10 publications

References 15 publications

Discovery of 2,6-Dihalopurines as Stomata Opening Inhibitors: Implication of an LRX-mediated H+-ATPase Phosphorylation Pathway

Discovery of 2,6-Dihalopurines as Stomata Opening Inhibitors: Implication of an LRX-mediated H+-ATPase Phosphorylation Pathway

Design, Synthesis, and Biological Evaluation of PKD Inhibitors

Synthesis and Structure−Activity Relationships of Benzothienothiazepinone Inhibitors of Protein Kinase D

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An Efficient Synthesis of 2‐Chloropyrimidines via Pd‐catalyzed Regioselective Dechlorination of 2,4‐Dichloropyrimidines in the Presence of NaHCO₃