A Sequential Suzuki Coupling Approach to Unsymmetrical Aryl s‐Triazines from Cyanuric Chloride

Abstract

A practical approach has been developed for efficient synthesis of unsymmetrical aryl striazines via highly selective sequential Suzuki coupling of cyanuric chloride (2,4,6-trichlorotriazine) with aryl or vinyl boronic or diarylborinic acids catalysed by 0.1-0.5 mol% Pd(PPh 3 ) 2 Cl 2 under mild conditions. The second and third Suzuki couplings for unsymmetrically trisubstituted aryl striazines could be more practically conducted in one-pot procedure. An electron-withdrawing conjugate group at phenyl ring of arylboronic acids was unexpectedly found to completely block the coupling while steric hindrance from an ortho electrondonating substituent could be overcome.

Design, Synthesis, In Vitro and In Vivo Characterization of CDC42 GTPase Interaction Inhibitors for the Treatment of Cancer

“…The preparation of the two triazine analogues required a different specific strategy due to the peculiar reactivity of cyanuric chloride (2,4,6-trichlorotriazine) 37 (Scheme ). It is well known that the C–Cl bond reactivity of the triazine substrate subsequently decreases from cyanuric chloride 37 to monochlorotriazine toward both metal cross-coupling and aromatic nucleophilic substitution transformations. , Accordingly, the orthogonal chemoselective substitution of thrichlorotriazine with the three specific functionalities of final compounds 28 and 29 was carefully evaluated, changing the reaction conditions and the order of synthetic sequence.…”

Strategic Advances in Sequential C-Arylations of Heteroarenes

“…Pd catalyzed C3–I arylation, and last, C2–Cl arylation afforded triarylpyridine, 129 (Scheme A). s -Triazines ( s = symmetric) bearing only chloro substituent can undergo selective arylations with the stoichiometric addition of aryl/diaryl boronic acids with respect to heteroarene and by using anhydrous/aqueous conditions . Zou and co-workers used PdCl 2 (PPh 3 ) 4 for the sequential functionalization of 130 , where C2 arylation takes place in anhydrous conditions with 1.5 eq of triazine, and C4 arylation required K 2 CO 3 (aq.…”

Late-Stage Sulfoximination: Improved Synthesis of the Anticancer Drug Candidate Atuveciclib

“…25 However, surprisingly no reaction occurred when 2,4-dichloro-1,3,5-triazine (3) and boronic acid 5 were mixed under the same conditions. 26 Finally, the last step consisted of the sulfoximination reaction that was performed using our previously described conditions: 15c PIDA (2.1 equiv), AC (1.5 equiv) in methanol at room temperature. After 30 minutes, complete conversion was observed and atuveciclib was obtained in 75% yield on gram scale after purification on silica gel.…”