83026-39-5Relevant academic research and scientific papers
Arylation of diethyl malonate and ethyl cyanoacetate catalyzed by palladium/di-tert-butylneopentylphosphine
Semmes, Jeffrey G.,Bevans, Stephanie L.,Mullins, C. Haddon,Shaughnessy, Kevin H.
supporting information, p. 3447 - 3450 (2015/02/05)
α-Arylated carbonyl derivatives are important structural motifs in many natural products and pharmaceutically active compounds. Although arylation of simple monocarbonyl compounds is a well-established methodology, metal-catalyzed arylation of β-dicarbonyl derivatives is significantly more challenging. The ability of β-dicarbonyl anions to bind to palladium in a κ2-O,O mode, rather than the κ1-C-bound mode required for bond formation, often results in the deactivation of catalyst systems. The C-bound form of the enolate can be favored through the use of sterically demanding ligands. Herein, we report that the sterically demanding di-tert-butylneopentylphosphine (DTBNpP) ligand in combination with Pd(dba)2 provides an effective catalyst for the coupling of aryl bromides and chlorides with diethyl malonate. The Pd/DTBNpP system also catalyzes the coupling of aryl bromides with ethyl cyanoacetate.
4-Amino-5-aryl-6-arylethynylpyrimidines: Structure-activity relationships of non-nucleoside adenosine kinase inhibitors
Matulenko, Mark A.,Paight, Ernest S.,Frey, Robin R.,Gomtsyan, Arthur,DiDomenico Jr., Stanley,Jiang, Meiqun,Lee, Chih-Hung,Stewart, Andrew O.,Yu, Haixia,Kohlhaas, Kathy L.,Alexander, Karen M.,McGaraughty, Steve,Mikusa, Joseph,Marsh, Kennan C.,Muchmore, Steven W.,Jakob, Clarissa L.,Kowaluk, Elizabeth A.,Jarvis, Michael F.,Bhagwat, Shripad S.
, p. 1586 - 1605 (2008/02/01)
A series of non-nucleoside adenosine kinase (AK) inhibitors is reported. These inhibitors originated from the modification of 5-(3-bromophenyl)-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4-ylamine (ABT-702). The identification of a linker that would approximate the spatial arrangement found between the pyrimidine ring and the aryl group at C(7) in ABT-702 was a key element in this modification. A search of potential linkers led to the discovery of an acetylene moiety as a suitable scaffold. It was hypothesized that the aryl acetylenes, ABT-702, and adenosine bound to the active site of AK (closed form) in a similar manner with respect to the orientation of the heterocyclic base. Although potent acetylene analogs were discovered based on this assumption, an X-ray crystal structure of 5-(4-dimethylaminophenyl)-6-(6-morpholin-4-ylpyridin-3-ylethynyl)pyrimidin-4-ylamine (16a) revealed a binding orientation contrary to adenosine. In addition, this compound bound tightly to a unique open conformation of AK. The structure-activity relationships and unique ligand orientation and protein conformation are discussed.
Palladium-catalyzed arylation of malonates and cyanoesters using sterically hindered trialkyl- and ferrocenyldialkylphosphine ligands
Beare, Neil A.,Hartwig, John F.
, p. 541 - 555 (2007/10/03)
Palladium-catalyzed reactions of aryl bromides and chlorides with two common stabilized carbanions - enolates of dialkyl malonates and alkyl cyanoesters - are reported. An exploration of the scope of these reactions was conducted, and the processes were shown to occur in a general fashion. Using P(t-Bu)3 (1), the pentaphenylferrocenyl ligand (Ph5C5)Fe(C5H4)P(t-Bu) 2 (2), or the adamantyl ligand (1-Ad)P(t-Bu)2 (3), reactions of electron-poor and electron-rich, sterically hindered and unhindered aryl bromides and chlorides were shown to react with diethyl malonate, di-tertbutyl malonate, diethyl fluoromalonate, ethyl cyanoacetate, and ethyl phenylcyanoacetate. Although alkyl malonates and ethyl alkylcyanoacetates did not react with aryl halides using these catalysts, the same products were formed conveniently in one pot from diethylmalonate by cross-coupling of an aryl halide in the presence of excess base and subsequent alkylation.
Ester Enolates from α-Acetoxy Esters. Synthesis of Aryl Malonic and α-Aryl Alkanoic Esters from Aryl Nucleophiles and α-Keto Esters
Ghosh, Subrata,Pardo, Simon N.,Salomon, Robert G.
, p. 4692 - 4702 (2007/10/02)
Ester enolates are generated by reductive α-deacetoxylation of α-acetoxy-α-arylmalonic esters or α-acetoxy-α-arylalkanoic esters with lithium in liquid ammonia or sodium α-(dimethylamino)naphthalenide in hexamethylphosphoramide-benzene.Since the requisite α-acetoxy esters are available from aryl nucleophiles, the reductions provide effective new synthetic routes to arylmalonic esters and α-arylalkanoic esters.For example, 2-(p-isobutylphenyl)propionic acid (ibuprofen, a commercially important nonsteroidal antiinflammatory agent) is obtained in 73percent yield overall from isobutylbenzene.Arenes, aryllithiums, or arylmagnesium halides react with α-keto esters, e.g., diethyl oxomalonate, ethyl pyruvate, methyl phenylglyoxalate, or alkyl glyoxylates, to afford α-hydroxy esters.These are acetylated with acetic anhydride-triethylamine and p-(dimethylamino)pyridine as a catalyst.Reductive α-deoxygenation then allows replacement of the acetoxy group by hydrogen or an alkyl group.
