Direct B-Alkyl Suzuki−Miyaura Cross-Coupling of 2-Halopurines. Practical Synthesis of ST1535, a Potent Adenosine A<sub>2A</sub> Receptor Antagonist

Bartoccini, Francesca; Cabri, Walter; Celona, Diana; Minetti, Patrizia; Piersanti, Giovanni; Tarzia, Giorgio

doi:10.1021/jo101027h

Cited by 15 publications

(9 citation statements)

References 36 publications

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“…264 The alkylation of these particular substrates was challenging but highly desirable, as it offers a concise route for the synthesis of ST1535, a potent adenosine A 2A receptor antagonist. Fortunately, applying a B -alkyl Suzuki-Miyaura cross-coupling in the presence of Cs 2 CO 3 and catalytic Pd (dppf)Cl 2 in THF afforded 2-alkylated purines in high yields.…”

Section: Cross-coupling With Alkylboron Reagentsmentioning

confidence: 99%

Advances in Transition Metal (Pd,Ni,Fe)-Catalyzed Cross-Coupling Reactions Using Alkyl-organometallics as Reaction Partners

2011

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Introduction 1418 1.1. List of Common Ligands 1419 2. Alkylzinc Reagents 1419 2.1. Synthesis of Alkylzinc Reagents 1419 2.2. Stability of Alkylzinc Reagents 1420 2.3. Cross-Coupling Reactions of Alkylzinc Reagents 1421 2.4. Palladium-Catalyzed Cross-Coupling Reactions of Alkylzinc Reagents 1423 2.4.1. Palladium-Catalyzed C(sp 2 )-C(sp 3 ) Negishi Coupling with Alkylzinc Reagents 1423 2.4.2. Palladium-Catalyzed C(sp 3 )-C(sp 3 ) Negishi Coupling with Alkylzinc Reagents 1427 2.4.3. Palladium-Catalyzed C(sp)-C(sp 3 ) Negishi Coupling with Alkylzinc Reagents 1428 2.4.4. Formation of Ketones via Palladium-Catalyzed Negishi Coupling with Alkylzinc Reagents 1429 2.5. Nickel-Catalyzed Cross-Coupling Reactions of Alkylzinc Reagents 1429 2.5.1. Nickel-Catalyzed C(sp 2 )-C(sp 3 ) Negishi Coupling with Alkylzinc Reagents 1429 2.5.2. Nickel-Catalyzed Carboxylations with Alkylzinc Reagents 1430 2.5.3. Nickel-Catalyzed C(sp 3 )--(sp 3 ) Negishi Coupling with Alkylzinc Reagents 1430 2.5.4. Mechanistic Insights in Nickel-Catalyzed Cross-Couplings 1433 3.

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Section: Cross-coupling With Alkylboron Reagentsmentioning

confidence: 99%

Advances in Transition Metal (Pd,Ni,Fe)-Catalyzed Cross-Coupling Reactions Using Alkyl-organometallics as Reaction Partners

2011

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“…Regioisomers were separated by flash chromatography on silica gel. [24,25] Scheme 10. Synthesis of compounds 45a-f in S N Ar reactions with azoles.…”

Section: C(8)-linked Azolylpurine Derivativesmentioning

confidence: 99%

“…[25] One can conclude that halopurines, inosine-and guanosine-derived sulfonate esters, and compounds possessing phosphorus-containing or O 6 -(benzotriazol-1-yl) leaving groups are suitable for the incorporation of azolyl groups in the purine system. The obtained 1,2,4-and 1,2,3-triazolylpurine derivatives can be used in further S N Ar reactions with other nucleophiles.…”

Section: C(8)-linked Azolylpurine Derivativesmentioning

confidence: 99%

“…The structures of these compounds indicated that medium-sized linear alkyl chains (CH 2 ) n CH 3 (where n Ͼ 2) or bulky alkyl chains [(CH 2 ) 2 Ph] promote affinity toward the adenosine A 2A receptor; in contrast, short or branched alkyl chains are not so active toward the receptor. [24,25] Other examples of observed biological activities of purine-azole conjugates are summarized in Table 9. Table 9.…”

Section: Biological Activitymentioning

confidence: 99%

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Synthesis and Applications of Azolylpurine and Azolylpurine Nucleoside Derivatives

2015

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Azolylpurines and azolylpurine nucleosides have important medicinal and biological applications. They are used as adenosine receptor agonists and antagonists and also as antivirals. Several compounds of this class exhibit fluorescent properties that can be applied in biological chemistry. This review summarizes and classifies all reported classes of purine‐azole conjugates, strategies for their syntheses, and suggestions of compound classes yet to be synthesized. Synthetic methodologies directed towards purine–azole conjugates, including SNAr reactions, cyclizations of amino‐ or hydrazinylpurines, and transition‐metal‐catalyzed cross‐coupling reactions, are discussed, as well as the use of selected azolylpurine derivatives as synthetic intermediates.

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“…More recently, during a study on the synthesis of ST1535, a potent adenosine A 2A receptor anatgonist, Bartoccini et al 185. found that 2‐ n ‐butyl‐ ( 505a ) and 2‐ethyl‐6‐chloro‐9‐methyl‐9 H ‐purines ( 505b ) could be efficiently and selectively synthesized by the PdCl 2 (dppf)‐catalyzed reaction of 6‐chloro‐2‐iodo‐9‐methylpurine ( 503 ) with 2.0 equiv.…”

Section: Cross‐coupling Reactions Of Polyhalogenated Heterocycle‐anmentioning

confidence: 99%

Selective Palladium‐Catalyzed Suzuki–Miyaura Reactions of Polyhalogenated Heteroarenes

2012

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The palladium-catalyzed Suzuki-Miyaura reaction of multiply halogenated, electron-rich and electron-deficient heteroarenes is one of the most reliable and environmentally friendly tools for installing a wide range of non-functionalized and functionalized carbon substituents onto heteroaromatic systems with exquisite chemo-and site-selectivity. For substrates with different halogen groups the chemoselectivity of the Suzuki-Miyaura reactions has been found to be dependent on the reactivity difference between the halogens. However, the hardest achievement of selectivity in Suzuki-Miyaura monocouplings involving polyhalogenated heteroarenes with identical halogen atoms has been shown to be dominated by steric and electronic effects and the presence of directing groups at positions neighbouring the reaction sites. Moreover, in the case of symmetrically substituted dihaloheteroarenes with identical halogen atoms, highly selective monocoupling reactions have often been achieved only after a careful optimization of reaction parameters including the catalyst precursor, base, solvent, and the molar ratio between electrophile and organoboron reagent. This critical review with 341 references covers developments on the chemo-and site-selective Suzuki-Miyaura monocoupling reactions of polyhalogenated heteroarenes with different or identical halogen atoms. It also includes the synthesis of polysubstituted heteroarenes, not easily accessible by other means, via consecutive monocoupling reactions and/ or a more synthetically valuable approach involving one-pot polycoupling reactions.

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Direct B-Alkyl Suzuki−Miyaura Cross-Coupling of 2-Halopurines. Practical Synthesis of ST1535, a Potent Adenosine A_2A Receptor Antagonist

Cited by 15 publications

References 36 publications

Advances in Transition Metal (Pd,Ni,Fe)-Catalyzed Cross-Coupling Reactions Using Alkyl-organometallics as Reaction Partners

Advances in Transition Metal (Pd,Ni,Fe)-Catalyzed Cross-Coupling Reactions Using Alkyl-organometallics as Reaction Partners

Synthesis and Applications of Azolylpurine and Azolylpurine Nucleoside Derivatives

Selective Palladium‐Catalyzed Suzuki–Miyaura Reactions of Polyhalogenated Heteroarenes

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Direct B-Alkyl Suzuki−Miyaura Cross-Coupling of 2-Halopurines. Practical Synthesis of ST1535, a Potent Adenosine A2A Receptor Antagonist

Cited by 15 publications

References 36 publications

Advances in Transition Metal (Pd,Ni,Fe)-Catalyzed Cross-Coupling Reactions Using Alkyl-organometallics as Reaction Partners

Advances in Transition Metal (Pd,Ni,Fe)-Catalyzed Cross-Coupling Reactions Using Alkyl-organometallics as Reaction Partners

Synthesis and Applications of Azolylpurine and Azolylpurine Nucleoside Derivatives

Selective Palladium‐Catalyzed Suzuki–Miyaura Reactions of Polyhalogenated Heteroarenes

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Product

Resources

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Direct B-Alkyl Suzuki−Miyaura Cross-Coupling of 2-Halopurines. Practical Synthesis of ST1535, a Potent Adenosine A_2A Receptor Antagonist