110969-44-3Relevant academic research and scientific papers
Aryl Amination Using Soluble Weak Base Enabled by a Water-Assisted Mechanism
Lau, Sii Hong,Yu, Peng,Chen, Liye,Madsen-Duggan, Christina B.,Williams, Michael J.,Carrow, Brad P.
supporting information, p. 20030 - 20039 (2021/01/01)
The amination of aryl halides has become one of the most commonly practiced C-N bond-forming reactions in pharmaceutical and laboratory syntheses. The widespread use of strong or poorly soluble inorganic bases for amine activation nevertheless complicates the compatibility of this important reaction class with sensitive substrates as well as applications in flow and automated synthesis, to name a few. We report a palladium-catalyzed C-N coupling using Et3N as a weak, soluble base, which allows a broad substrate scope that includes bromo- and chloro(hetero)arenes, primary anilines, secondary amines, and amide type nucleophiles together with tolerance for a range of base-sensitive functional groups. Mechanistic data have established a unique pathway for these reactions in which water serves multiple beneficial roles. In particular, ionization of a neutral catalytic intermediate via halide displacement by H2O generates, after proton loss, a coordinatively unsaturated Pd-OH species that can bind amine substrate triggering intramolecular N-H heterolysis. This water-assisted pathway operates efficiently with even weak terminal bases, such as Et3N. The use of a simple, commercially available ligand, PAd3, is key to this water-assisted mechanism by promoting coordinative unsaturation in catalytic intermediates responsible for the heterolytic activation of strong element-hydrogen bonds, which enables broad compatibility of carbon-heteroatom cross-coupling reactions with sensitive substrates and functionality.
Synthesis of Nitrogen-Containing Goniothalamin Analogues with Higher Cytotoxic Activity and Selectivity against Cancer Cells
Meirelles, Matheus A.,Braga, Carolyne B.,Ornelas, Catia,Pilli, Ronaldo A.
supporting information, p. 1403 - 1417 (2019/08/01)
Two series of racemic goniothalamin analogues displaying nitrogen-containing groups were designed and synthesized. A total of 19 novel analogues were evaluated against a panel of four different cancer cell lines, along with the normal prostate cell line PNT2 to determine their selectivity. Among them, goniothalamin chloroacrylamide 13 e displayed the lowest IC50 values for both MCF-7 (0.5 μm) and PC3 (0.3 μm) cells, about 26-fold more potent than goniothalamin (1). Besides its higher potency, compound 13 e also displayed much higher selectivity than goniothalamin. In contrast, goniothalamin isobutyramide 13 c was the most potent analogue against Caco-2 cells (IC50=0.8 μm), about 10-fold more potent and 17-fold more selective than 1. These results reveal the potential of compounds 13 c and 13 e for further in vivo studies, representing the first goniothalamin analogues with IC50 values in the low micromolar range and high selectivity against MCF-7, Caco-2, and PC3 cancer cell lines.
MECHANISTIC TARGET OF RAPAMYCIN SIGNALING PATHWAY INHIBITORS AND THERAPEUTIC APPLICATIONS THEREOF
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Paragraph 00128; 00129; 00130, (2018/04/11)
Selective mTOR inhibitors of formulas (I)-(III), processes for their preparation, pharmaceutical compositions containing them, and their use in the treatment of diseases and disorders, arising from abnormal cell growth, functions, or behaviors mediated by an mTOR kinase and/or one or more PI3K enzyme, are provided. Such diseases and disorder include cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine function disorders and neurological disorders.
ORGANIC REACTIONS CARRIED OUT IN AQUEOUS SOLUTION IN THE PRESENCE OF A HYDROXYALKYL(ALKYL)CELLULOSE OR AN ALKYLCELLULOSE
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Page/Page column 217; 222; 223, (2017/08/21)
The present invention relates to a method of carrying out an organic reaction in aqueous solution in the presence of a hydroxyalkyl(alkyl)cellulose or an alkylcellulose.
Installation of protected ammonia equivalents onto aromatic & heteroaromatic rings in water enabled by micellar catalysis
Isley, Nicholas A.,Dobarco, Sebastian,Lipshutz, Bruce H.
supporting information, p. 1480 - 1488 (2014/03/21)
A single set of conditions consisting of a palladium catalyst, a commercially available ligand, and a base, allow for several types of C-N bond constructions to be conducted in water with the aid of a commercially available "designer" surfactant (TPGS-750-M). Products containing a protected NH2 group in the form of a carbamate, sulfonamide, or urea can be fashioned starting with aryl or heteroaryl bromides, iodides, and in some cases, chlorides, as substrates. Reaction temperatures are in the range of room temperature to, at most, 50 °C, and result in essentially full conversion and good isolated yields.
"nok": A phytosterol-based amphiphile enabling transition-metal-catalyzed couplings in water at room temperature
Klumphu, Piyatida,Lipshutz, Bruce H.
, p. 888 - 900 (2014/03/21)
The third-generation designer amphiphile/surfactant, "Nok" (i.e., SPGS-550-M; β-sitosterol methoxypolyethyleneglycol succinate), soon to be commercially available from Aldrich, can be prepared in two steps using an abundant plant feedstock and β-sitosterol, together with succinic anhydride and PEG-550-M. Upon dissolution in water, it forms nanomicelles that serve as nanoreactors, which can be characterized by both cryo-TEM and dynamic light scattering analyses. Several transition-metal-catalyzed reactions have been run under micellar conditions to evaluate this surfactant relative to results obtained in nanoparticles composed of TPGS-750-M (i.e., a second-generation surfactant). It is shown that Nok usually affords yields that are, in general, as good or better than those typically obtained with TPGS-750-M, and yet is far less costly.
A selective turn-on fluorescent probe for Cd2+ based on a boron difluoride β-dibenzoyl dye and its application in living cells
Xin, Li,Chen, Yu-Zhe,Niu, Li-Ya,Wu, Li-Zhu,Tung, Chen-Ho,Tong, Qing-Xiao,Yang, Qing-Zheng
, p. 3014 - 3019 (2013/07/26)
Herein we report the first example of a difluoroboron dibenzoyl based fluorescent probe for Cd2+ detection. The probe displays high selectivity and sensitivity toward Cd2+ over Zn2+ in aqueous solution under physiological conditions. Fluorescence imaging experiments demonstrate its potential application for detecting Cd2+ in living cells. The Royal Society of Chemistry 2013.
Palladium-catalyzed amidation of aryl halides using 2-dialkylphosphino- 2′-alkoxyl-1,1′-binaphthyl as ligands
Ma, Fangfang,Xie, Xiaomin,Zhang, Lei,Peng, Zhiyong,Ding, Lina,Fu, Lei,Zhang, Zhaoguo
experimental part, p. 5279 - 5285 (2012/08/07)
Palladium-catalyzed intermolecular C-N bond-forming reactions between aryl halides and amides are described using 2-dialkylphosphino-2′-alkoxyl-1, 1′-binaphthyl, which is both bulky and electron-rich, as the ligand. A variety of amides, including aliphatic and aromatic primary amides, lactams, and carbamates, were viable substrates for the amidation, which exhibited good functional group compatibility. By tuning the substituents at the 2,2′-position of 1,1′-binaphthyl of the ligand, the palladium-catalyzed amidation of bulky aryl halides was realized and this coupling reaction was used to synthesize 2-amino-2′-methoxy-1,1′- binaphthyl in high yield.
IMIDAZOLYL PYRIMIDINE INHIBITOR COMPOUNDS
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Page/Page column 36-37, (2010/02/17)
A compound of general Formula (I) having histone deacetylase (HDAC) and/or Cyclin-dependent kinase (CDK) inhibitory activity, a pharmaceutical composition comprising the compound, and a method useful to treat diseases using the compound.
PYRIMIDINYL-PYRAZOLE INHIBITORS OF AURORA KINASES
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Page/Page column 42-43, (2010/11/26)
The present invention provides a compound represented by Formula (I): or a pharmaceutically acceptable salt thereof, or a solvate thereof, or a combination thereof, wherein the substituents are as defined herein. The present invention also relates to a co
