- Iron-catalyzed direct C-H arylation of heterocycles and quinones with arylboronic acids
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The arylation of C-H bonds to generate heteroaryl-aryl (Het-Ar) and arylated quinone (Quin-Ar) compounds has received great attention to achieve sustainable goals in synthetic chemistry. Despite significant advances, arylation of a broad range of Het-Ar and Quin-Ar derivatives remains a challenging task. Herein, a variety of heterocycles are arylated by using arylboronic acids in the presence of catalytic amounts of inexpensive Fe(NO 3)3. The C-arylated quinone compounds can be prepared by reacting arylboronic acids with either quinone or hydroquinone. The present method is operationally simple, scalable, does not require prefunctionalization of the heterocycle or quinone, and can tolerate a wide variety of functional groups in the coupling partners. These qualities are expected to render this method attractive for academic and industrial use. Direct C-H arylation of a variety of heterocycles and quinones with arylboronic acids has been developed. An inexpensive iron catalyst, Fe(NO3)3, and a co-oxidant, persulfate, were used in air. The protocol is applicable for large-scale synthesis and is expected to find application as a result of its operational simplicity. Copyright
- Deb, Arghya,Manna, Srimanta,Maji, Arun,Dutta, Uttam,Maiti, Debabrata
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supporting information
p. 5251 - 5256
(2013/09/02)
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- 9-Hydroxyazafluorenes and their use in thrombin inhibitors
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Optimization of a previously reported thrombin inhibitor, 9-hydroxy-9-fluorenylcarbonyl-L-prolyl-trans-4-aminocyclohexylmethylamide (1), by replacing the aminocyclohexyl P1 group provided a new lead structure, 9-hydroxy-9-fluorenylcarbonyl-L-prolyl-2-aminomethyl-5-chlorobenzylamide (2), with improved potency (Ki = 0.49 nM for human thrombin, 2× APTT = 0.37 μM in human plasma) and pharmacokinetic properties (F = 39%, iv T1/2 = 13 h in dogs). An effective strategy for reducing plasma protein binding of 2 and improving efficacy in an in vivo thrombosis model in rats was to replace the lipophilic fluorenyl group in P3 with an azafluorenyl group. Systematic investigation of all possible azafluorenyl P3 isomers and azafluorenyl-N-oxide analogues of 2 led to the identification of an optimal compound, 3-aza-9-hydroxyfluoren-9(R)-ylcarbonyl-L-prolyl-2-aminomethyl-5- chlorobenzylamide (19b), with high potency (Ki = 0.40 nM, 2× APTT = 0.18 μM), excellent pharmacokinetic properties (F = 55%, T 1/2 = 14 h in dogs), and complete efficacy in the in vivo thrombosis model in rats (inhibition of FeCl3-induced vessel occlusions in six of six rats receiving an intravenous infusion of 10 μg/kg/min of 19b). The stereochemistry of the azafluorenyl group in 19b was determined by X-ray crystallographic analysis of its N-oxide derivative (23b) bound in the active site of human thrombin.
- Stauffer, Kenneth J.,Williams, Peter D.,Selnick, Harold G.,Nantermet, Philippe G.,Newton, Christina L.,Homnick, Carl F.,Zrada, Matthew M.,Lewis, S. Dale,Lucas, Bobby J.,Krueger, Julie A.,Pietrak, Beth L.,Lyle, Elizabeth A.,Singh, Rominder,Miller-Stein, Cynthia,White, Rebecca B.,Wong, Bradley,Wallace, Audrey A.,Sitko, Gary R.,Cook, Jacquelyn J.,Holahan, Marie A.,Stranieri-Michener, Maria,Leonard, Yvonne M.,Lynch Jr., Joseph J.,McMasters, Daniel R.,Yan, Youwei
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p. 2282 - 2293
(2007/10/03)
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- DECOMPOSITION DU PEROXYDE DE BENZOYLE DANS DES MELANGES CARBOMETHOXY-4 PYRIDINE/BENZENE
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The decomposition kinetics of benzoyl peroxide in 4-carbomethoxy-pyridine and in 4-carbomethoxy-pyridine/benzene have been studied in the presence and absence of inhibitor.The rate constant for the radical induced decomposition of benzoyl peroxide was 2.6E-4 l/mol*s in 4-carbomethoxy-pyridine, and in benzene it was 9.2E-6 l/mol*s, a thirty fold decrease.A mechanism including the attack at the nitrogen atom of the pyridine ring by the phenyl radical and the oxidation of the sigma-complex by the 1-phenyl-4-carbomethoxy pyridinium ion has been proposed.The system of the differential equations obtained from the proposed mechanism has been numerically solved.
- Court, J.,Vidal, S.,Bonnier, J. M.
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p. 6623 - 6632
(2007/10/02)
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