458-85-5Relevant articles and documents
Cu-Catalyzed Site-Selective Benzylic Chlorination Enabling Net C–H Coupling with Oxidatively Sensitive Nucleophiles
Lopez, Marco A.,Buss, Joshua A.,Stahl, Shannon S.
supporting information, p. 597 - 601 (2022/01/20)
Site-selective chlorination of benzylic C–H bonds is achieved using a CuICl/bis(oxazoline) catalyst with N-fluorobenzenesulfonimide as the oxidant and KCl as a chloride source. This method exhibits higher benzylic selectivity, relative to estab
N-(Pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinolin-6-amine Derivatives as Selective Janus Kinase 2 Inhibitors for the Treatment of Myeloproliferative Neoplasms
Yang, Tao,Hu, Mengshi,Chen, Yong,Xiang, Mingli,Tang, Minghai,Qi, Wenyan,Shi, Mingsong,He, Jun,Yuan, Xue,Zhang, Chufeng,Liu, Kongjun,Li, Jiewen,Yang, Zhuang,Chen, Lijuan
, p. 14921 - 14936 (2020/12/22)
In this study, we described a series of N-(pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinolin-6-amine derivatives as selective JAK2 (Janus kinase 2) inhibitors. Systematic exploration of the structure-activity relationship though cyclization modification based on previously reported compound 18e led to the discovery of the superior derivative 13ac. Compound 13ac showed excellent potency on JAK2 kinase, SET-2, and Ba/F3V617F cells (high expression of JAK2V617F mutation) with IC50 values of 3, 11.7, and 41 nM, respectively. Further mechanistic studies demonstrated that compound 13ac could downregulate the phosphorylation of downstream proteins of JAK2 kinase in cells. Compound 13ac also showed good selectivity in kinase scanning and potent in vivo antitumor efficacy with 82.3% tumor growth inhibition in the SET-2 xenograft model. Moreover, 13ac significantly ameliorated the disease symptoms in a Ba/F3-JAK2V617F allograft model, with 77.1% normalization of spleen weight, which was more potent than Ruxolitinib.
Aminoazanium of DABCO: An Amination Reagent for Alkyl and Aryl Pinacol Boronates
Liu, Xingxing,Zhu, Qing,Chen, Du,Wang, Lu,Jin, Liqun,Liu, Chao
, p. 2745 - 2749 (2020/01/25)
The aminoazanium of DABCO (H2N-DABCO) has been developed as a general and practical amination reagent for the direct amination of alkyl and aryl pinacol boronates. This compound is stable and practical for use as a reagent. Various primary, secondary. and tertiary alkyl?Bpin and aryl?Bpin substrates were aminated to give the corresponding amine derivatives. The amination is stereospecific. The anti-Markovnikov hydroamination of olefins was easily achieved by catalytic hydroboration with HBpin and in subsequent situ amination using H2N-DABCO. Moreover, the combination of 1,2-diboration of olefins, using B2pin2, with this amination process achieved the unprecedented 1,2-diamination of olefins. The amination protocol was also successfully extended to aryl pinacol boronates.
Amination reagent as well as preparation method and application thereof
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Paragraph 0115-0117; 0148-0149; 0151, (2020/03/12)
The invention discloses an amination reagent as well as a preparation method and application thereof. The amination reagent has a structure as shown in a formula disclosed in the invention, wherein Xis selected from any one of I, Cl, Br, NO3 and ClO4, and Y and Z are independently selected from H or alkyl with the carbon atom number of 1-4. The process for preparing the amination reagent is simple, the raw materials are easy to obtain, the cost is low, the yield is stable, and the prepared amination reagent is stable in character, can be stored at room temperature for a long time and can be taken as needed; meanwhile, the prepared amination reagent is efficient in performance, boron substrate applicability is excellent, reaction effect is good, and limitation of amination reaction of organic boron compounds on substrates is greatly expanded.
Overcoming inaccessibility of fluorinated imines-synthesis of functionalized amines from readily available fluoroacetamides
Czerwiński, Pawe? J.,Furman, Bart?omiej
supporting information, p. 9436 - 9439 (2019/08/15)
Although imines are convenient substrates for the synthesis of functionalized amines, they may be hard to obtain, as in the case of fluorinated imines. To aid in overcoming this issue, we propose a protocol of corresponding amine synthesis from simple fluoroacetic acid-derived amides using Schwartz's reagent.
Oxidative Amide Coupling from Functionally Diverse Alcohols and Amines Using Aerobic Copper/Nitroxyl Catalysis
Piszel, Paige E.,Vasilopoulos, Aristidis,Stahl, Shannon S.
supporting information, p. 12211 - 12215 (2019/07/31)
The aerobic Cu/ABNO catalyzed oxidative coupling of alcohols and amines is highlighted in the synthesis of amide bonds in diverse drug-like molecules (ABNO=9-azabicyclo[3.3.1]nonane N-oxyl). The robust method leverages the privileged reactivity of alcohol
Synthesis method of glibenclamide
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Paragraph 0048; 0055, (2018/04/26)
The invention discloses a synthesis method of glibenclamide, which includes the steps of: 1) protection of amino groups with trichloroacetic anhydride; 2) sulfonation; 3) sulfo-amidation; 4) amidation: performing a reaction to 5-chloro-2-methoxybenzoic acid with N,N-carbonyl diimidazole and performing a reaction to the product with a compound (III) under effect of a second acid-binding agent; 5) addition: adding the second acid-binding agent and crown ether, in catalytic amount, to perform an addition reaction to a compound (IV) with cyclohexyl isocyanate to prepare the glibenclamide. The method is high in yields in all steps, wherein residue of impurities is effectively reduced during processes of protection, deprotection, acid treatment, alkali treatment and water-adding separation of the substrate. According to the method, a phase-transfer catalyst is matched with the second acid-binding agent, so that compatibility between the isocyanate and the compound (IV) is effectively increased, and the nucleophilic reaction is carried out more completely. The produced product is higher in purity.
meta-Selective C?H Borylation of Benzylamine-, Phenethylamine-, and Phenylpropylamine-Derived Amides Enabled by a Single Anionic Ligand
Davis, Holly J.,Genov, Georgi R.,Phipps, Robert J.
supporting information, p. 13351 - 13355 (2017/10/07)
Selective functionalization at the meta position of arenes remains a significant challenge. In this work, we demonstrate that a single anionic bipyridine ligand bearing a remote sulfonate group enables selective iridium-catalyzed borylation of a range of common amine-containing aromatic molecules at the arene meta position. We propose that this selectivity is the result of a key hydrogen bonding interaction between the substrate and catalyst. The scope of this meta-selective borylation is demonstrated on amides derived from benzylamines, phenethylamines and phenylpropylamines; amine-containing building blocks of great utility in many applications.
Hexamethyldisilazane as an acylation generator for perfluorocarboxylic acids in quantitative derivatization of primary phenylalkyl amines confirmed by GC/MS and computations
Molnr, Borbla,Csmpai, Antal,Molnr-Perl, Ibolya
, p. 848 - 852 (2015/02/19)
A novel, selective acylation of primary phenylalkyl amines (PPAAs) using hexamethyldisilazane (HMDS) and perfluorocarboxylic acids (PFCAs) is noted. Couples, like HMDS and trifluoroacetic acid, HMDS and pentafluoropropionic acid, or HMDS and heptafluorobutyric acid trigger PPAAs' quantitative acylation. Processes' selectivity was characterized by applying all couples to derivatize benzyl, 2-phenylethyl, 3-phenylpropyl, 4-phenylbutyl amines, and their relevant substituted versions. Aliphatic amines were unreactive. Identification, quantification, proportionality, and stoichiometry in derivatization processes were determined by gas chromatography/mass spectrometry. Reaction conditions were optimized depending on reagents' molar ratios, solvents, and temperatures applied. The new acylation method, in comparison to the traditional ones, obtained with trifluoroacetic anhydride, heptafluorobutyric anhydride, and N-methyl-bis(trifluoroacetamide), offers numerous advantages. Derivatives, provided by couples, can be directly injected onto the column, avoiding loss of species, saving time, work, and cost in the preparation process. Due to traditional reagents' excess evaporation by nitrogen drying, the loss of trifluoroacylated species proved to be 65% or less. Regarding heptafluorobutyryl species, their losses varied between 25% and 5%. Unified huge responses, obtained with the HMDS and PFCA couples are attributable to their direct injection onto the column and to fragments sourced from the molecular ions and from their self-chemical ionization ([M]?+, [M+147]+, i.e., [M+(CH3)2-Si=O-Si-(CH3)3]+). The reaction mechanism, due to the HMDS symmetrical structure, acting HMDS as acylation generator for PFCAs, was confirmed by density functional theory (DFT) computation.
Quantitative Silylation Speciations of Primary Phenylalkyl Amines, Including Amphetamine and 3,4-Methylenedioxyamphetamine Prior to Their Analysis by GC/MS
Molnár, Borbála,Fodor, Blanka,Boldizsár, Imre,Molnár-Perl, Ibolya
, p. 10188 - 10192 (2015/11/09)
A novel, quantitative trimethylsilylation approach derivatizing 11 primary phenylalkyl amines (PPAAs), including amphetamine (A) and 3,4-methylenedioxyamphetamine (MDA), was noted. Triggering the fully derivatized ditrimethylsilyl (diTMS) species with the N-methyl-N-(trimethylsilyl)-trifluoroacetamide (MSTFA) reagent, a new principle was recognized followed by GC/MS. In the course of method optimization, the complementary impact of solvents (acetonitrile, ACN; ethyl acetate, ETAC; pyridine, PYR) and catalysts (trimethylchlorosilane, TMCS; trimethyliodosilane, TMIS) was studied: the role of solvent and catalyst proved to be equally crucial. Optimum, proportional, huge responses were obtained with the MSTFA/PYR = 2/1-9/1 (v/v) reagent applying catalysts; A and MDA needed the TMIS, while the rest of PPAAs provided the diTMS products also with TMCS. Similar to derivatives generated with hexamethyldisilazane and perfluorocarboxylic acid (HMDS and PFCA) (Molnár et al. Anal. Chem. 2015, 87, 848'852), the fully silylated PPAAs offer several advantages. Both of our methods save time and cost by allowing for direct injection of analytes into the column; this is in stark contrast with the requirement to evaporate acid anhydrides by nitrogen prior to their injection. Efficiences of the novel catalyzed trimethylsilylation (MSTFA) and our recently introduced (now, for A and MDA extended) acylation principle were contrasted. Catalyzed trimethylsilylation led to diTMS derivatives resulting in on average a 1.7 times larger response compared to the corresponding acylated species. Catalyzed trimethylsilylation of PPAAs, A, and MDA were characterized with retention, mass fragmentation, and analytical performance properties (R2, LOQ values). The practical utility of ditrimethylsilyation was shown by analyzing A in urine and mescaline (MSC) in cactus samples.
