- 4-Dimethylaminopyridine-catalyzed synthesis of isothiocyanates from amines and carbon disulfide
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Isothiocyanates were synthesized by reactions between primary amines and CS2 in the presence of 4-dimethylaminopyridine as a catalyst and tert-butyl hydroperoxide as an oxidant. Various aryl, benzyl, alkyl, and hydroxyl amines were transformed into the corresponding isothiocyanates in 41–82% yields.
- Rong, Hao-Jie,Chen, Tao,Xu, Ze-Gang,Su, Tian-Duo,Shang, Yu,Wang, Yong-Qiang,Yang, Cui-Feng
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- Synthesis method of 2-aminothiazole pyrimidine serving as CDK2 inhibitor
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The invention relates to the technical field of organic synthesis and medicines, and particularly discloses a synthesis method of 2-aminothiazole pyrimidine serving as a CDK/2 inhibitor. The synthesismethod comprises the following steps: converting amino into isothiocyanate, reacting the isothiocyanate with primary amine to generate thiourea, and carrying out Hantzsch thiazole synthesis reaction,fluorination reaction and condensation of enaminone and guanidine hydrochloride to form a pyrimidine ring. According to the method, through five steps of reactions, the total yield reaches 35%-48%. The method has the advantages that a traditional fluorination method is replaced by photocatalysis; the yield of the whole process is greatly increased, the yield is increased to 85% from 35% through the fluorination reaction, and compared with a traditional fluorination method in a low-temperature ice salt bath, the method is milder in condition, only needs to be carried out at the room temperature, and is a good process for synthesizing the CDK/2 inhibitor 2-aminothiazole pyrimidine.
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Paragraph 0026-0027
(2021/03/06)
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- Pyrazolopyrimidines: Potent Inhibitors Targeting the Capsid of Rhino- and Enteroviruses
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There are currently no drugs available for the treatment of enterovirus (EV)-induced acute and chronic diseases such as the common cold, meningitis, encephalitis, pneumonia, and myocarditis with or without consecutive dilated cardiomyopathy. Here, we report the discovery and characterization of pyrazolopyrimidines, a well-tolerated and potent class of novel EV inhibitors. The compounds inhibit the replication of a broad spectrum of EV in vitro with IC50 values between 0.04 and 0.64 μM for viruses resistant to pleconaril, a known capsid-binding inhibitor, without affecting cytochrome P450 enzyme activity. Using virological and genetics methods, the viral capsid was identified as the target of the most promising, orally bioavailable compound 3-(4-trifluoromethylphenyl)amino-6-phenylpyrazolo[3,4-d]pyrimidine-4-amine (OBR-5-340). Its prophylactic as well as therapeutic application was proved for coxsackievirus B3-induced chronic myocarditis in mice. The favorable pharmacokinetic, toxicological, and pharmacodynamics profile in mice renders OBR-5-340 a highly promising drug candidate, and the regulatory nonclinical program is ongoing. Curing the common cold! A cluster of pyrazolopyrimidines with potent broad-spectrum activity against enteroviruses was discovered. Extensive structure-property relationship analyses led to the identification of 3-(4-trifluoromethyl-phenyl)amino-6-phenylpyrazolo[3,4-d]pyrimidine-4-amine, shown to be a blocker of the viral capsid protein, as a lead compound for drug development with favorable physicochemical, pharmacokinetic, and toxicological properties.
- Makarov, Vadim A.,Braun, Heike,Richter, Martina,Riabova, Olga B.,Kirchmair, Johannes,Kazakova, Elena S.,Seidel, Nora,Wutzler, Peter,Schmidtke, Michaela
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supporting information
p. 1629 - 1634
(2015/10/06)
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- A new efficient synthesis of isothiocyanates from amines using di-tert-butyl dicarbonate
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Alkyl and aryl amines are converted smoothly to the corresponding isothiocyanates via the dithiocarbamates in good to excellent yields using di-tert-butyl dicarbonate (Boc2O) and 1-3 mol % of DMAP or DABCO as catalyst. As most of the byproducts are volatile, the work-up involves simple evaporation of the reaction mixture.
- Munch, Henrik,Hansen, Jon S.,Pittelkow, Michael,Christensen, J?rn B.,Boas, Ulrik
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p. 3117 - 3119
(2008/09/20)
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- The Improved Phosphoramidate Route to Isothiocyanates
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Moderate yields of isothiocyanates prepared by the Wadsworth-Emmons approach can be essentially improved when the reaction is carried out in the presence of catalytic amounts of tetrabutylammonium bromide.
- Olejniczak, Bogdan,Zwierzak, Andrzej
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p. 300 - 301
(2007/10/02)
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