- Cu-Catalyzed Site-Selective Benzylic Chlorination Enabling Net C–H Coupling with Oxidatively Sensitive Nucleophiles
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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
- Lopez, Marco A.,Buss, Joshua A.,Stahl, Shannon S.
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supporting information
p. 597 - 601
(2022/01/20)
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- N-(Pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinolin-6-amine Derivatives as Selective Janus Kinase 2 Inhibitors for the Treatment of Myeloproliferative Neoplasms
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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.
- 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
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p. 14921 - 14936
(2020/12/22)
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- Aminoazanium of DABCO: An Amination Reagent for Alkyl and Aryl Pinacol Boronates
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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.
- Liu, Xingxing,Zhu, Qing,Chen, Du,Wang, Lu,Jin, Liqun,Liu, Chao
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p. 2745 - 2749
(2020/01/25)
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- Amination reagent as well as preparation method and application thereof
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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.
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Paragraph 0115-0117; 0148-0149; 0151
(2020/03/12)
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- Oxidative Amide Coupling from Functionally Diverse Alcohols and Amines Using Aerobic Copper/Nitroxyl Catalysis
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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
- Piszel, Paige E.,Vasilopoulos, Aristidis,Stahl, Shannon S.
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supporting information
p. 12211 - 12215
(2019/07/31)
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- Overcoming inaccessibility of fluorinated imines-synthesis of functionalized amines from readily available fluoroacetamides
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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.
- Czerwiński, Pawe? J.,Furman, Bart?omiej
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supporting information
p. 9436 - 9439
(2019/08/15)
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- Synthesis method of glibenclamide
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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.
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Paragraph 0048; 0055
(2018/04/26)
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- meta-Selective C?H Borylation of Benzylamine-, Phenethylamine-, and Phenylpropylamine-Derived Amides Enabled by a Single Anionic Ligand
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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.
- Davis, Holly J.,Genov, Georgi R.,Phipps, Robert J.
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supporting information
p. 13351 - 13355
(2017/10/07)
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- Hexamethyldisilazane as an acylation generator for perfluorocarboxylic acids in quantitative derivatization of primary phenylalkyl amines confirmed by GC/MS and computations
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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.
- Molnr, Borbla,Csmpai, Antal,Molnr-Perl, Ibolya
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p. 848 - 852
(2015/02/19)
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- Quantitative Silylation Speciations of Primary Phenylalkyl Amines, Including Amphetamine and 3,4-Methylenedioxyamphetamine Prior to Their Analysis by GC/MS
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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.
- Molnár, Borbála,Fodor, Blanka,Boldizsár, Imre,Molnár-Perl, Ibolya
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p. 10188 - 10192
(2015/11/09)
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- Iridium-catalyzed asymmetric intramolecular allylic amidation: Enantioselective synthesis of chiral tetrahydroisoquinolines and saturated nitrogen heterocycles
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For the first time iridium catalysis has been used for the synthesis of chiral tetrahydroisoquinolines with excellent yields and high enantioselectivities (see scheme; cod=1,5-cyclooctadiene, DBU=1,8- diazabicyclo[5.4.0]undec-7-ene). These products are important chiral building blocks for the synthesis of biologically active compounds, in particular alkaloids. Copyright
- Teichert, Johannes F.,Fananas-Mastral, Martin,Feringa, Ben L.
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supporting information; experimental part
p. 688 - 691
(2011/04/18)
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- Convenient one-pot synthesis of N-substituted 3-trifluoroacetyl pyrroles
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A new one-pot strategy for the synthesis of a series of new N-substituted 3-trifluoroacetyl pyrroles is presented. These compounds were obtained by the reaction of 3-trifluoroacetyl-4,5-dihydrofuran with primary amines, which generated 1,1,1-trifluoro-3-(2-hydroxyethyl)-4-alkylaminobut-3-en-2-one intermediates. In most cases these intermediates were not stable enough to be isolated. Thus, in the same reaction vessel they were directly submitted to oxidation with PCC (Corey's reagent) to furnish 1,1,1-trifluoro-3-(2-ethanal)-4- alkylaminobut-3-en-2-ones, which under reflux underwent intramolecular cyclization to give the desired N-substituted 3-trifluoroacetyl pyrroles, in moderate yields. All of these pyrroles were tested against pan-susceptible Mycobacterium tuberculosis H37Rv and clinical isolates INH- and RMP-resistant strain and some of these compounds showed significant in vitro antimicrobial activity. Georg Thieme Verlag Stuttgart.
- Zanatta, Nilo,Wouters, Ana D.,Fantinel, Leonardo,Da Silva, Fabio M.,Barichello, Rosemário,Da Silva, Pedro E. A.,Ramos, Daniela F.,Bonacorso, Helio G.,Martins, Marcos A. P.
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experimental part
p. 755 - 758
(2009/07/18)
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- Direct ortho iodination of β- and γ-aryl alkylamine derivatives
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Two in one! A trifluoroacetamide protecting group not only masks an amine functionality, but also mimics peptidyl directing effects as a controlling unit in an efficient ortho iodination of a variety of biologically relevant small molecules (see example). (Chemical Equation Presented).
- Barluenga, Jose,Alvarez-Gutierrez, Julia M.,Ballesteros, Alfredo,Gonzalez, Jose M.
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p. 1281 - 1283
(2008/03/27)
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- 5-AMIDINO-2-HYDROXYBENZENESULFONAMIDE DERIVATIVES, MEDICINAL COMPOSITIONS CONTAINING THE SAME, MEDICINAL USE THEREOF AND INTERMEDIATES IN THE PRODUCTION THEREOF
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The present invention relates to a 5-amidino-2-hydroxybenzenesulfonamide derivative represented by the general formula: wherein R1 is an optionally substituted lower alkyl group, an optionally substituted lower alkoxy group, an optionally substituted lower alkenyl group, a cycloalkyl group or a lower acyl group etc.; Q is a hydrogen atom or an optionally substituted lower alkyl group; and Z is a hydrogen atom or a hydroxy group etc., or a pharmaceutically acceptable salt thereof, which exert a potent and selective activated blood coagulation factor X inhibitory activity and is useful as an agent for the prevention or treatment of a disease occurred associating an activated blood coagulation factor X, a pharmaceutical composition comprising the same and an intermediate thereof. These compounds are useful as preventives or remedies for various diseases such as brain infarction, cerebral thrombosis, cerebral embolism, TIA, cerebral vascular jerk, Alzheimer's diseases, myocardial infarction, heart attack, heart failure, thrombosis, pulmonary infarction and pulmonary embolism.
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- BENZOTHIAZOLE DERIVATIVES HAVING BETA-2-ADRENORECEPTOR AGONIST ACTIVITY
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Compounds of Formula (I) in free or salt or solvate form, wherein X has the meaning indicated in the specification, are useful for treating conditions that are prevented or alleviated by activation of the ?2-adrenoreceptor. Pharmaceutical compositions that contain the compounds and processes for preparing the compounds are also described.
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- Aminoalcohol derivatives
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The present invention relates to a compound formula [I]: wherein R1 is hydrogen or halogen, R2 is hydrogen or an amino protective group, R3 is hydrogen or lower alkyl, X is bond, —CH2— or —O—, and Y is ?in which R4 is lower alkoxycarbonyl, ?in which R5 is carboxy(lower)alkyl, etc., ?in which R6 is hydroxy, etc., and so on, or a salt thereof. The compound [I] of the present invention and pharmaceutically acceptable salts thereof are useful for the prophylactic and/or the therapeutic treatment of pollakiurea or urinary incontinence.
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Page/Page column 8-9
(2010/02/07)
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- Sulfonamide derivatives
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The present invention provides certain sulfonamide derivatives useful for potentiating glutamate receptor function in a patient and therefore, useful for treating a wide variety of conditions, such as psychiatric and neurological disorders.
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- Anti-herpesvirus compounds and methods for identifying, making and using same
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This invention relates to methods for inhibiting herpes replication and for treating herpes infection in a mammal by inhibiting the herpes helicase-primase enzyme complex. This invention also relates to thiazolyphenyl derivatives that inhibit the herpes helicase-primase and to pharmaceutical compositions comprising the thiazolylphenyl derivatives, to methods of using and methods of producing the thiazolylphenyl derivatives.
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- A convenient trifluoroacetylation reagent: N- (trifluoroacetyl)succinimide
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N-(Trifluoroacetyl)succinimide, easily prepared from trifluoroacetic anhydride and succinimide forms a novel, convenient trifluoroacetylating reagent. It trifluoroacetylates alcohols, phenols and mines, to generate trifluoroacetate esters, and trifluoroacetamides in excellent yields with very efficient work up procedures.
- Katritzky, Alan R.,Yang, Baozhen,Guofang, Qiu,Zhang, Zhongxing
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- AMIDINE DERIVATIVES WITH NITRIC OXIDE SYNTHETASE ACTIVITIES
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Amidine derivative compounds of formula I as defined in the Specification having nitric oxide synthetase inhibitory activity as well as processes for the preparation of and compositions containing said compounds are described
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- Preparation of 1,2,3,4-tetrahydroisoquinolines lacking electron donating groups - An intramolecular cyclization complementary to the Pictet-Spengler reaction
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The synthesis of 1,2,3,4-tetrahydroisoquinolines via an intramolecular cyclization of N-trifluoroacylated phenethylamines devoid of electron donating groups, with paraformaldehyde mediated by acetic/sulfuric acid milieu is described.
- Stokker
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p. 5453 - 5456
(2007/10/03)
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- 1-(p-Substituted or unsubstituted aminoalkyl)phenylpropane-1,2-dione bis(thiosemicarbazone) derivatives, and their production and use
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A radioactive diagnostic agent which comprises a physiologically active substance and a radioactive metallic element combined with a compound of the formula: STR1 wherein R, R', R1 and R2 are each a hydrogen atom or a C1 -
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- Friedel-Crafts Acylation with N-(Trifluoroacetyl)-α-amino Acid Chlorides. Application to the Preparation of β-Arylalkylamines and 3-Substituted 1,2,3,4-Tetrahydroisoquinolines
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Several N-(trifluoroacetyl)-α-amino acid chlorides have been reacted with benzene, anisole, and veratrole in the presence of AlCl3 or SnCl4 to produce the corresponding aromatic ketones in fair to high yields.The products are reductible under neutral or acidic conditions to the corresponding N-(trifluoroacetyl)-β-hydroxy-β-arylakylamines or N-(trifluoroacetyl)-β-arylalkylamines.The latter can be readily detrifluoroacetylated by mild basic hydrolysis and thence converted to the corresponding 3-substituted 1,2,3,4-tetrahydroisoquinolines by condensation with formaldehyde.
- Nordlander, Eric J.,Payne, Mark J.,Njoroge, George F.,Balk, Michael A.,Laikos George D.,Vishwanath, Vasanth M.
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p. 4107 - 4111
(2007/10/02)
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- NOVEL CONDENSING AGENTS FOR BISCHLER-NAPIERALSKI TYPE CYCLODEHYDRATION
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Trifluoroacetic anhydride and trifluoromethyl sulfonyl anhydride are used in Bischler-Napieralski type cyclization.Starting from the appropriate amides, the dihydroisoquinolines are formed in excellent yields.
- Nagubandi, Sreeramulu,Fodor, G.
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p. 165 - 177
(2007/10/02)
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