Synthesis and biological evaluation of allenic quinazolines using palladium-catalyzed hydride-transfer reaction

Synthesis and Reactivity of Propargylamines in Organic Chemistry

“…On the basis of the same principle of anion equivalency, the same authors attempted to introduce allenic groups into the backbone of pharmacologically active molecules in order to produce new pharmacological properties . Allenic quinazolines 1029 were synthesized from the coupling of corresponding iodides 1027 and dicyclohexyl-propargylamine via Sonogashira/hydrogen-transfer reactions (Scheme ).…”

Allene as an Alternative Functional Group for Drug Design: Effect of CC Multiple Bonds Conjugated with Quinazolines on the Inhibition of EGFR Tyrosine Kinase

“…[23][24][25] We were therefore interested in the utility of allene as an alternative functional group for pharmaceutical drug design, and we focused on an acetylene moiety in Tarceva. [26] According to the X-ray crystal structure, the acetylene group is located in the hydrophobic kinase pocket of EGFR. [27] Herein we demonstrate the effect of CÀC multiple bonds in quinazolines on the inhibition of EGFR tyrosine kinase activity by replacement with allenyl, vinyl, and ethyl groups in the framework.…”

1,2-Bis(diphenylphosphino)carborane As a Dual Mode Ligand for Both the Sonogashira Coupling and Hydride-Transfer Steps in Palladium-Catalyzed One-Pot Synthesis of Allenes from Aryl Iodides

“…The proper choice of ligands for transition-metal-catalyzed reactions is crucial for expanding the scope of reactions in organic synthesis . We recently found the allene transformation from propargylic amines via palladium-catalyzed hydride-transfer reaction . In this transformation, propargylic amines can be handled as an allenyl anion equivalent, which reacts with various aryl halides and heterocyclic halides through the Sonogashira coupling reaction to be transformed into allenes.…”

“…In this transformation, propargylic amines can be handled as an allenyl anion equivalent, which reacts with various aryl halides and heterocyclic halides through the Sonogashira coupling reaction to be transformed into allenes. Although trispentafluorophenylphosphine [(C 6 F 5 ) 3 P] was found to be a potent ligand for the palladium-catalyzed hydride-transfer reaction, it was not effective for the Sonogashira coupling step 2a. Therefore, two separate steps were needed for the synthesis of allenes from organic halides ( 1 → 3 → 4 pathway in Scheme ).…”

“…The use of P(OPh) 3 as a ligand increased the yield of 4a (40%, entry 2). However, the reaction did not proceed in the presence of P(C 6 F 5 ) 3 ligand, which is effective for the palladium-catalyzed hydride-transfer step (entry 3) 2a. Although the reactions failed with various bidentate phosphine ligands, such as bis(diphenylphosphino)methane (dppm), 1,2-bis(diphenylphosphino)ethane (dppe), and 1,1‘-bis(diphenylphosphino)ferrocene (dppf), (C 6 F 5 ) 2 PC 2 H 4 P(C 6 F 5 ) 2 was found to be effective for both the Sonogashira coupling and hydride-transfer steps and 4a was obtained in 87% yield, exclusively (entry 4).…”