Efficient Construction of the Nucleus of Rosuvastatin Calcium

Abstract

A novel and efficient five‐step synthetic route, including a Biginelli reaction, dehydrogenation, chlorination, sulfonamidation, and reduction, for the core of Rosuvastatin was established. All steps were systematically studied. Tert‐butylhydroperoxide aqueous solution was applied in the dehydrogenation instead of nitric acid. N,N‐dimethylaniline was employed as a catalyst to accelerate the chlorination proceeding smoothly, and its catalytic mechanism is discussed. In the sulfonamidation, the conversion of compound 5 was obviously improved by use of NaH and acetonitrile. In addition, two sulfonamidation side products 6 and 7 were detected and isolated. Thus, under the optimized reaction conditions, the target product was obtained in 60.4% total yield, much higher than the reported yield (36.4%).

Interrogation of 2,2′-Bipyrimidines as Low-Potential Two-Electron Electrolytes

“…Importantly, the first two steps in the sequence have been reported to be highly scalable (∼400 kg scale, conditions i and iii) 37 without the need for purification (products 1 and 2 could be obtained cleanly through a simple filtration in most cases). Converting 2-hydroxypyrimidines (2) to their respective 2chloropyrimidines (3) proceeded smoothly through the use of POCl 3 (condition v), 39 with the exception of acid-sensitive esters which required the use of Appel type conditions (condition vi). 40,41 Finally, a Ni-catalyzed homocoupling, originally developed for the synthesis of bipyridines by Weix and co-workers, could be adapted to the synthesis of the desired bipyrimidine products (4).…”

“…Converting 2-hydroxypyrimidines ( 2 ) to their respective 2-chloropyrimidines ( 3 ) proceeded smoothly through the use of POCl 3 (condition v), with the exception of acid-sensitive esters which required the use of Appel type conditions (condition vi). , Finally, a Ni-catalyzed homocoupling, originally developed for the synthesis of bipyridines by Weix and co-workers, could be adapted to the synthesis of the desired bipyrimidine products ( 4 ) . While these conditions were not optimized for a particular substrate, it was discovered that some minor changes could furnish the products with higher efficiency (see SI for details).…”

N-Directed Pd-Catalyzed Photoredox-Mediated C–H Arylation for Accessing Phenyl-Extended Analogues of Biginelli/Suzuki-Derived Ethyl 4-Methyl-2,6-diphenylpyrimidine-5-carboxylates

“…Access to multi-substituted pyrimidines, by means of C2 modification of 3,4-DHPMs, to eventually form a C-heteroatom or C-C bond, requires prior aromatization of Biginelli products [10][11][12][13][14] and conversion of the resulting C2-OH to a good leaving group, such as halide or sulfonate (Scheme 1) [31][32][33]. This is eventually replaced by nucleophiles [34][35][36] or submitted to cross-coupling reactions [37][38][39][40].…”