931-53-3Relevant articles and documents
One-Pot Synthesis of Thiocarbamates
Barther, Dennis,Malliaridou, Triantafillia,Meier, Michael A. R.,Moatsou, Dafni,Waibel, Kevin A.
supporting information, p. 4508 - 4516 (2021/08/30)
An efficient isocyanide-based synthesis of S-thiocarbamates was discovered and thoroughly investigated. The new reaction protocol is a one-pot procedure and allows the direct conversion of N-formamides into thiocarbamates by initial dehydration with p-toluene sulfonyl chloride to the respective isocyanide and subsequent addition of a sulfoxide component. Contrary to recent literature, which also uses isocyanides as starting material, but with other sulfur reagents than sulfoxides, in this protocol, no isolation and purification of the isocyanide component is necessary, thus significantly decreasing the environmental impact and increasing the efficiency of the synthesis. The new protocol was applied to synthesize a library of sixteen thiocarbamates, applying four N-formamides and four commercially available sulfoxides. Furthermore, experiments were conducted to investigate the reaction mechanism. Finally, four norbornene-based thiocarbamate monomers were prepared and applied in controlled ring-opening metathesis polymerization (ROMP) reactions. The polymers were characterized by size-exclusion chromatography (SEC) and their properties were investigated utilizing differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA).
A more sustainable and highly practicable synthesis of aliphatic isocyanides
Waibel,Nickisch,M?hl,Seim,Meier
supporting information, p. 933 - 941 (2020/02/21)
Synthesis protocols to convert N-formamides into isocyanides using three different dehydration reagents (i.e. p-toluenesulfonyl chloride (p-TsCl), phosphoryl trichloride (POCl3) and the combination of triphenylphosphane (PPh3) and iodine) were investigated and optimized, while considering the principles of green chemistry. Comparison of the yield and the E-factors of the different synthesis procedures revealed that, in contrast to the typically applied POCl3 or phosgene derivatives, p-TsCl was the reagent of choice for non sterically demanding aliphatic mono- or di-N-formamides (yields up to 98% and lowest E-factor 6.45). Apart from a significantly reduced E-factor, p-TsCl is cheap, offers a simplified reaction protocol and work-up, and is less toxic compared to other dehydration reagents. Thus, this procedure offers easier and greener access to aliphatic isocyanide functionalities.
Tandem reaction strategy of the Passerini/Wittig reaction based on the in situ capture of isocyanides: One-pot synthesis of heterocycles
Liu, Ming-Guo,Liu, Na,Xu, Wen-Heng,Wang, Long
, p. 2748 - 2754 (2019/04/04)
This paper reports the tandem reaction strategy of the Passerini/Wittig reaction based on the in situ capture of isocyanides. According to this strategy, plenty of isocyanides have been synthesized, which is immediately used for the tandem reaction of Passerini/Wittig reaction in one pot. Compared to the previous work, this strategy avoids the separation, purification, and storage of isocyanides, which prominently solves the problems of isocyanide-based multicomponent reaction such as: (a) The environmentally unfriendly (strong foul odor), (a) the labile of Isocyanides, (c) high toxicity of isocyanides. In the meantime, in order to expand the application scope of our strategy, 1H-isochromenes and 3H-2-benzoxepin-1-ones have also been synthesized, which undergoes four-step transformations in one-pot. In addition, a relatively credible reaction mechanism has also been proposed, based on a series of control experiments. Furthermore, preliminary testing was performed on biological activity of some obtained compounds; These results showed that the synthesized compounds exhibited certain activity over P. digitatum and P. italicum. 2019 Elsevier Science. All rights reserved.
Odorless Isocyanide Chemistry: One-Pot Synthesis of Heterocycles via the Passerini and Postmodification Tandem Reaction Based on the in Situ Capture of Isocyanides
Liu, Na,Chao, Fei,Liu, Ming-Guo,Huang, Nian-Yu,Zou, Kun,Wang, Long
, p. 2366 - 2371 (2019/05/16)
This paper reports the tandem reaction strategy of the Passerini/Staudinger/aza-Wittig reaction based on the in situ capture of isocyanides. According to this strategy, isocyanides are synthesized in situ and immediately work as the substrate for the Passerini reaction and postmodification tandem reaction in one pot. In addition, two types of new compounds, 5-oxo-3,5-dihydrobenzo[e][1,4]oxazepines and 6-oxo-5,6-dihydro-2H-1,4-oxazines, were synthesized using the tandem reaction strategy that includes five-step transformations in one pot.
Facile, catalyst-free cascade synthesis of sulfonyl guanidines: Via carbodiimide coupling with amines
Hazarika, Debojit,Borah, Arun Jyoti,Phukan, Prodeep
supporting information, p. 1418 - 1421 (2019/02/05)
An expeditious catalyst-free cascade coupling of N,N-dibromoarylsulfonamides with isonitriles and amines via carbodiimide intermediates has been developed. The protocol represents an elegant pathway for sulfonyl guanidines at room temperature within a short time with high yields and wide substrate scope. The carbodiimide intermediate could also be isolated in an appreciable yield.
Discovery of AG-120 (Ivosidenib): A First-in-Class Mutant IDH1 Inhibitor for the Treatment of IDH1 Mutant Cancers
Popovici-Muller, Janeta,Lemieux, René M.,Artin, Erin,Saunders, Jeffrey O.,Salituro, Francesco G.,Travins, Jeremy,Cianchetta, Giovanni,Cai, Zhenwei,Zhou, Ding,Cui, Dawei,Chen, Ping,Straley, Kimberly,Tobin, Erica,Wang, Fang,David, Muriel D.,Penard-Lacronique, Virginie,Quivoron, Cyril,Saada, Véronique,De Botton, Stéphane,Gross, Stefan,Dang, Lenny,Yang, Hua,Utley, Luke,Chen, Yue,Kim, Hyeryun,Jin, Shengfang,Gu, Zhiwei,Yao, Gui,Luo, Zhiyong,Lv, Xiaobing,Fang, Cheng,Yan, Liping,Olaharski, Andrew,Silverman, Lee,Biller, Scott,Su, Shin-San M.,Yen, Katharine
supporting information, p. 300 - 305 (2018/04/20)
Somatic point mutations at a key arginine residue (R132) within the active site of the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) confer a novel gain of function in cancer cells, resulting in the production of d-2-hydroxyglutarate (2-HG), an oncometabolite. Elevated 2-HG levels are implicated in epigenetic alterations and impaired cellular differentiation. IDH1 mutations have been described in an array of hematologic malignancies and solid tumors. Here, we report the discovery of AG-120 (ivosidenib), an inhibitor of the IDH1 mutant enzyme that exhibits profound 2-HG lowering in tumor models and the ability to effect differentiation of primary patient AML samples ex vivo. Preliminary data from phase 1 clinical trials enrolling patients with cancers harboring an IDH1 mutation indicate that AG-120 has an acceptable safety profile and clinical activity.
One-step synthesis of N, N′-substituted 4-imidazolidinones by an isocyanide-based pseudo-five-multicomponent reaction
Attorresi, Cecilia I.,Bonifazi, Evelyn L.,Ramírez, Javier A.,Gola, Gabriel F.
supporting information, p. 8944 - 8949 (2018/12/10)
A pseudo-five-multicomponent reaction involving an isocyanide, a primary amine, two molecules of formaldehyde and water is reported, which gives N,N′-substituted 4-imidazolidinones when trifluoroethanol is used as the solvent. The reaction proceeds with good yields and with a wide variety of amines and isocyanides, providing an efficient new entry to these heterocycles. A preliminary study of the reaction mechanism suggests that trifluoroethanol, although acting as the solvent, is directly involved as a reagent in the reaction pathway.
2-Isocyano glucose used in Ugi four-component reaction: An approach to enhance inhibitory effect against DNA oxidation
Zhao, Peng-Fei,Liu, Zai-Qun
, p. 458 - 466 (2017/05/05)
The Ugi four-component-reaction (Ugi 4CR) allowed synthesizing bisamide from carboxylic acid, aldehyde, amine, and isocyanide in one-pot operation. However, introducing 2-isocyano glucose into the Ugi 4CR and investigating the inhibitory effects of Ugi adducts against radical-induced oxidation of DNA remained technical challenges. We herein applied 2-isocyano glucose (acetylation of hydroxy groups) to perform a catalyst-free Ugi 4CR at room temperature. The gallic, ferulic, caffeic, or p-hydroxybenzoic acids, aniline (or benzylamine and p-aminophenol), and formaldehyde acted as reagents. In the case of inhibiting DNA oxidations induced by 2,2’-azobis(2-amidinopropane hydrochloride) (AAPH), hydroxy radical, and Cu2+/glutathione, the Ugi adduct containing glucose moiety exhibited higher antioxidative activities than the structural analog without glucose moiety involved. It was also proved that high antioxidative property was owing to hydroxy groups in glucose moiety. Therefore, sugar-appended Ugi adducts might hold promising inhibitors for DNA oxidation.
Synthesis and structure–activity relationship of α-keto amides as enterovirus 71 3C protease inhibitors
Zeng, Debin,Ma, Yuying,Zhang, Rui,Nie, Quandeng,Cui, Zhengjie,Wang, Yaxin,Shang, Luqing,Yin, Zheng
supporting information, p. 1762 - 1766 (2016/12/22)
α-Keto amide derivatives as enterovirus 71 (EV71) 3C protease (3Cpro) inhibitors have been synthesized and assayed for their biochemical and antiviral activities. structure–activity relationship (SAR) study indicated that small moieties were primarily tolerated at P1' and the introduction of para-fluoro benzyl at P2 notably improved the potency of inhibitor. Inhibitors 8v, 8w and 8x exhibited satisfactory activity (IC50= 1.32 ± 0.26 μM, 1.88 ± 0.35 μM and 1.52 ± 0.31 μM, respectively) and favorable CC50values (CC50> 100 μM). α-Keto amide may represent a good choice as a warhead for EV71 3Cproinhibitor.
Efficient isocyanide-less isocyanide-based multicomponent reactions
Neochoritis, Constantinos G.,Stotani, Silvia,Mishra, Bhupendra,D?mling, Alexander
supporting information, p. 2002 - 2005 (2015/04/27)
Isocyanides are the Jekyll and Hyde of organic chemistry allowing for extremely interesting transformations that are not only extremely odorous but also noxious. Therefore, an isocyanide-less isocyanide-based multicomponent reaction (IMCR) has been developed, and this protocol is expected to replace many of the old procedures in the future not only in IMCR but in other areas of organic chemistry as well.
