- Preparation method of acetenyl aniline
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The invention discloses a preparation method of acetenyl aniline, wherein the preparation method comprises the following steps: by using nitroethylbenzene as a raw material and MBr-MBrO3-H2SO4 (M=Na or K) as a bromination reagent, carrying out free radical bromination reaction to prepare 1,1-dibromo-1-(nitrophenyl)ethane, carrying out elimination reaction under the action of alkali to obtain nitrophenylacetylene, and finally, carrying out Fe/HCl reduction to obtain acetenyl aniline. The preparation method provided by the invention has the advantages of cheap and easily available raw materials, simple and safe operation, good reaction selectivity, high product yield, less emission of three wastes and the like.
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Paragraph 0055; 0058-0059; 0062-0063; 0066-0067; 0070-0071
(2021/04/14)
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- Preparation method of m-aminophenylacetylene
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The invention discloses a preparation method of m-aminophenylacetylene, belonging to the technical field of organic synthesis. The method comprises the following steps of: subjecting m-nitroacetophenone serving as a raw material to reacting with triethyl phosphite under the action of a catalyst, continuously converting the m-nitroacetophenone into enol form, and condensing the enol form with the triethyl phosphite to obtain condensation ester, wherein the condensation ester is easy to separate and high in purity, m-nitrophenylacetylene is generated from the ester under the action of strong base, and m-aminophenylacetylene is generated from the ester through reduction. Compared with an acetophenone chlorination method, the method of the invention has the advantages that phosphorus oxychloride does not need to be used for changing oxygen of the m-nitroacetophenone into chlorine, pollution is small, purity is high ( 98% or more), the use of high-pollution raw material reagents is avoided, operation is simple, the environment-friendly effects are realized, and industrial production can be conveniently realized.
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Paragraph 0008; 0023
(2021/05/29)
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- Fast heck-cassar-sonogashira (hcs) reactions in green solvents
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The replacement of toxic solvents with greener alternatives in Heck-Cassar-Sonogashira (HCS) cross-couplings was investigated. The fine-tuning of the HCS protocol allowed to achieve complete conversions and high speed under mild conditions. N-Hydroxyethylpyrrolidone (HEP) gave the best results. Moreover, the methodology was successfully applied to the synthesis of an intermediate of the anticancer drug Erlotinib, demonstrating the versatility of the new green protocol.
- Cabri, W.,Corbisiero, D.,Daka, A.,Fantoni, T.,Ferrazzano, L.,Martelli, G.,Ricci, A.,Tolomelli, A.,Viola, A.
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supporting information
p. 3969 - 3973
(2020/06/08)
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- Differences in the selective reduction mechanism of 4-nitroacetophenone catalysed by rutile- And anatase-supported ruthenium catalysts
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Ru/TiO2 catalysts exhibit excellent catalytic performance for selective reduction of 4-nitroacetophenone to 4-aminoacetophenone at normal temperature and atmospheric hydrogen pressure. Moreover, 99.9% selectivity to 4-aminoacetophenone can be obtained over 2.7 wt% Ru/TiO2(anatase) catalyst even in a relatively wide temperature (55-115 °C) and time (1-12 h) range. Its excellent catalytic performance is derived from the activation of H2 on the Ru nanoparticles at atmospheric pressure and the strong interaction of nitro groups with the support surface. Additionally, Ru nanoparticles supported on different crystalline TiO2 phases (anatase and rutile) result in different reaction pathways for 4-nitroacetophenone. Since the Ti-Ti distance on the rutile surface is smaller than that on the anatase surface, the hydroxylamine species adsorbed on the Ti atoms of rutile are more susceptible to the coupling reaction. Therefore, Ru/TiO2(rutile) causes a series of intermediates to accumulate during the conversion process, while Ru/TiO2(anatase) allows the highly selective conversion of 4-nitroacetophenone to 4-aminophenone. In addition, Ru/TiO2(anatase) can achieve chemoselective reduction of nitroaromatics to the corresponding anilines in the presence of -CN, -CHO, and -COOH, especially nitroaromatics containing CC and CC, indicating the excellent applicability.
- Gu, Xianmo,Pei, Linjuan,Wang, Jie,Zhang, Jin,Zheng, Zhanfeng,Zhu, Pengqi
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p. 1518 - 1528
(2020/03/26)
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- Design, synthesis and biological evaluation of novel uracil derivatives bearing 1, 2, 3-triazole moiety as thymidylate synthase (TS) inhibitors and as potential antitumor drugs
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Research on thymidylate synthase inhibitors has been a hot spot for anticancer drug development. Here, based on the structures and pharmacological properties of two types of TS inhibitors, through a molecular assembly principle of drugs design, we designed and synthesized a series of 30 novel uracil derivatives as TS inhibitors. The antiproliferative ability of these compounds was evaluated against four cancer cell lines (A549, OVCAR-3, SGC-7901, and HepG2) by the MTT assay. Most of them showed excellent activities against all the tested cell lines. Furthermore, hTS assay results showed that these compounds have the unique ability to inhibit hTS activity in vitro. Notably, compound 13j exhibited the most potent activity against A549 cells (IC50 = 1.18 μM) and extremely prominent enzyme inhibition (IC50 = 0.13 μM), which was superior to the pemetrexed (PTX, IC50 = 3.29 μM and IC50 = 2.04 μM). Flow cytometric analysis showed the compound 13j could inhibit A549 cells proliferation by arresting the cell cycle in the G1/S phase, then induced the cell apoptosis. Further western blot analysis showed that compound 13j could down-regulate the cycle checkpoint proteins cyclin D1 and cyclin E to inhibit the cell cycle progression, and then induce intrinsic apoptosis by activating caspase-3, and reducing the ratio of bcl-2/bax. All of these results demonstrated that this new structure has potential drug-making properties and provides new ideas for drug development.
- Lu, Guo-qing,Li, Xin-yang,Mohamed O, Kamara,Wang, Depu,Meng, Fan-hao
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p. 282 - 296
(2019/03/27)
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- Design, synthesis, and structure-activity relationship of 7-propanamide benzoxaboroles as potent anticancer agents
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Benzoxaboroles, as a novel class of bioactive molecules with unique physicochemical properties, have been shown to possess excellent antimicrobial activities with tavaborole approved in 2014 as an antifungal drug. Although urgently needed, the investigation of benzoxaboroles as anticancer agents has been lacking so far. In this study, we report the design, synthesis, and anticancer structure-activity relationship of a series of 7-propanamide benzoxaboroles. Compounds 103 and 115 showed potent activity against ovarian cancer cells with IC50 values of 33 and 21 nM, respectively. Apoptosis was induced by these compounds and colony formation was effectively inhibited. Furthermore, they also showed excellent efficacy in ovarian tumor xenograft mouse model.
- Zhang, Jiong,Zhang, Jinyi,Hao, Guiyun,Xin, Weixiang,Yang, Fei,Zhu, Mingyan,Zhou, Huchen
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p. 6765 - 6784
(2019/08/20)
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- Ultradispersed Nickel Phosphide on Phosphorus-Doped Carbon with Tailored d-Band Center for Efficient and Chemoselective Hydrogenation of Nitroarenes
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Nickel phosphide is a promising catalyst for hydrogenation of nitroarenes but suffers from sluggish H desorption and low chemoselectivity. Herein, we overcome these problems through reducing the Ni2P into subnanosized clusters, tailoring the d-band center of Ni, and coupling them with P-doped carbon. Using density functional theory (DFT) calculations, we predicted that electron transfer from P-doped carbon to Ni2P cluster results in downshift of d-band center of Ni that promotes H desorption on highly charged antibonding orbital of Ni-H, and reactant is preferentially adsorbed on P-doped carbon surface through nitro group due to the geometrical hindrance on Ni2P clusters that leads to good selectivity. Then we developed a chemical anchoring method to fabricate Ni2P supported on P-doped carbon with high dispersion of 81.3%. The synthesized catalyst delivers high activity and selectivity chemoselective hydrogenation of nitroarenes, and outperforms various noble- and transition-metal catalysts. Moreover, we revealed the origins of the superior performance of catalyst by characterizations, and confirmed the conclusion of DFT calculation. Such concept of tailoring d-band center and improving dispersion of active phase can provide insight for design of catalysts for hydrogenation and beyond.
- Gao, Ruijie,Pan, Lun,Wang, Huiwen,Zhang, Xiangwen,Wang, Li,Zou, Ji-Jun
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p. 8420 - 8429
(2018/09/06)
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- Preparation method of 3-aminophenylacetylene
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The invention discloses a preparation method of 3-aminophenylacetylene. The preparation method of 3-aminophenylacetylene comprises the steps: with nitrobenzene as a starting raw material, firstly, synthesizing 3-nitrophenylacetylene by photocatalysis; and then, synthesizing 3-aminophenylacetylene. Therefore, a target product of 3-aminophenylacetylene is high in yield, few in byproducts, low in cost, safe and environmentally friendly.
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Page/Page column 7; 8; 9
(2018/11/03)
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- Preparation method of 3-aminophenylacetylene
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The invention relates to the field of organic synthesis, in particular to a preparation method of 3-aminophenylacetylene. The preparation method of 3-aminophenylacetylene comprises the following steps: preparing a compound shown as formula III from a compound shown as formula I and a compound shown as formula II through a coupling reaction; preparing a compound shown as formula V from the compoundshown as the formula III. The preparation method of 3-aminophenylacetylene is short in synthetic route, low in energy consumption and environmentally friendly, and the target product can be obtainedparticularly from 3-bromophenylacetylene as a raw material through two steps of reactions. Besides, prepared 3-aminophenylacetylene is used as a raw material of an anticancer drug, so that generationof potential genotoxic impurities containing halogen and ethylenic linkage structures can be avoided effectively from the source.
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Paragraph 0115; 0116; 0118
(2018/09/13)
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- A synthesis method of erlotinib hydrochloride (by machine translation)
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The invention relates to a technical field of drug synthesis, relates to a new synthetic method of erlotinib hydrochloride. The steps are as follows: 1) to acetophenone as a starting material, in the nitration reaction takes place in the mixed between nitro acetophenone; 2) between nitro acetophenone with chlorinated reagent in the organic solvent in the reaction of chloride 1 - chloro - 1 - (3 - nitrophenyl) ethylene; 3) 1 - chloro - 1 - (3 - nitrophenyl) ethylene in the presence of an organic solvent and alkali to obtain between the dehydrochlorination nitrobenzene acetylene; 4) m acetylene through the nitro-selective reduction to obtain between amino acetylene; reduction method as a reducing agent or catalytic hydrogenation reduction; 5) between amino acetylene and 4 - chloro - 6, 7 - b - (2 - methoxyethoxy) quinazoline in reaction of organic solvent to obtain the erlotinib hydrochloride; raw materials of the invention is cheap, low production cost, simple operation, mild reaction conditions and the like, and is suitable for industrial production. (by machine translation)
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Paragraph 0046; 0047; 0048; 0049; 0050; 0051
(2017/06/30)
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- Ruthenium nanoparticle-catalyzed, controlled and chemoselective hydrogenation of nitroarenes using ethanol as a hydrogen source
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This communication describes a ruthenium nanoparticle-catalyzed reduction of nitroarenes giving azoxyarenes, azoarenes, or anilines in good to excellent yields using ethanol as a hydrogen source. Copyright
- Kim, Ju Hyun,Park, Ji Hoon,Chung, Young Keun,Park, Kang Hyun
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supporting information
p. 2412 - 2418
(2012/11/07)
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- New method for the preparation of erlotinib
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The present invention refers to an alternative method for the preparation of Erlotinib through a new chemical reaction for the preparation of the 4-(3-aminophenyl)-2-methyl-3-butyn-2-ol key intermediate of formula (IV) according to the following scheme.
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- METHOD FOR THE PREPARATION OF ERLOTINIB
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An alternative method for the preparation of Erlotinib through a new chemical reaction for the preparation of the 4-(3-aminophenyl)-2-methyl-3-butyn-2-ol key intermediate of formula (IV) according to the following scheme.
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- Diruthenium phenylacetylide complexes bearing para -/ meta -amino phenyl substituents
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Presented herein is the synthesis and characterization of four diruthenium(II,III) compounds of formulas Ru2(Xap) 4(C≡C-C6H4-4-NH2) (Xap is 2-anilinopyridinate, 1a; and 2-(3,5-dimethoxy)anilinopyridinate, 1b) and Ru 2(Xap)4(C≡C-C6H4-3-NH 2) (2a/2b). X-ray structural studies of compounds 1b and 2a revealed minimal changes in the coordination sphere of the Ru2 core. Voltammetric measurements showed that compounds 1 exhibit three one-electron redox processes: a reversible reduction of Ru2, a reversible oxidation of Ru2, and a quasi-reversible oxidation of an amino group. Compounds 2 display the same Ru2-based redox processes but not the -NH2 oxidation. Compounds 1a/1b were successfully converted to the corresponding diazonium salts [Ru2(Xap)4-(C≡C-C 6H4-4-N2)](BF4) (3a/3b) via oxidation by nitrosonium tetrafluoroborate, which was generated in situ from t-BuONO and BF3. However, the attempt to convert compounds 2 to the corresponding diazonium salts was unsuccessful. DFT calculations of model compounds were performed to rationalize some unusual structural and electrochemical characteristics observed for compounds 1/2.
- Cummings, Steven P.,Cao, Zhi,Liskey, Carl W.,Geanes, Alex R.,Fanwick, Phillip E.,Hassell, Kerry M.,Ren, Tong
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experimental part
p. 2783 - 2788
(2010/08/06)
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- METHOD OF PRODUCING ETHYNYL COMPOUND, METHOD OF HANDLING ETHYNYL COMPOUND, AND METHOD OF USING ASCORBIC ACID OR SALT THEREOF
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A method of producing a first ethynyl compound represented by the following formula (1), the method including reacting a second ethynyl compound represented by the following formula (2) in a liquid phase in the presence of a reducing agent to obtain the first ethynyl compound, wherein Q1 represents an organic group; R1 and R2 each independently represent a hydrogen atom or a hydrocarbon group; and R1 and R2 may be bonded to each other.
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Page/Page column 6
(2008/12/09)
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- Combination therapy of her expressing tumors
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The invention relates to tumors expressing HER2 and EGFR, using HER2-dimerization inhibitors (HDIs) and EGFR inhibitors.
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Page/Page column 59-60
(2008/06/13)
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- Process for preparing 3-aminophenylacetylenes
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A process for preparing a 3-aminophenylacetylene compound of formula (5), including: a) reacting a 3-haloaniline compound of formula (1) with an acetylene compound of formula (2) in the presence of a palladium compound, a copper compound, and an amine compound of formula (3) to form an aniline compound of formula (4); b) precipitating the aniline compound of formula (4) in the form of a crystal, and isolating it by solid/liquid separation; and c) reacting the aniline compound of formula (4) with a base to obtain 3-aminophenylacetylene.
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Page/Page column 8-9
(2008/06/13)
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- Methods of using death receptor agonists and EGFR inhibitors
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Methods for using death receptor ligands, such as Apo-2 ligand/TRAIL polypeptides or death receptor antibodies, and EGFR inhibitors to treat pathological conditions such as cancer are provided. Embodiments of the invention include methods of using Apo2L/TRAIL or death receptor antibodies such as DR5 antibodies and DR4 antibodies in combination with EGFR inhibitors, such as Tarceva?.
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Page/Page column 35-36
(2008/06/13)
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- Stable polymorph of N-(3-ethynylphenyl)-6, 7-bis (2-methoxyethoxy)-4-quinazolinamine hydrochloride, methods of production, and pharmaceutical uses thereof
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The present invention relates to a stable crystalline form of N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine hydrochloride designated the B polymorph, its production in essentially pure form, and its use. The invention also relates to the pharmaceutical compositions containing the stable polymorph B form of N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine as hydrochloride, as well other forms of the compound, and to methods of treating hyperproliferative disorders, such as cancer, by administering the compound.
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Page/Page column 16
(2008/06/13)
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- FUSED BICYCLIC PYRIMIDINE DERIVATIVES
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The invention relates to compounds of the formula 1and to pharmaceutically acceptable salts thereof, wherein R1, R2 and Z are as defined herein. The invention also relates to pharmaceutical compositions containing the compounds of formula I and to methods of using said compounds in the treatment of hyperproliferative diseases such as cancer.
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- Preparation of 2′-aminoacetophenones: A one-pot hydration and reduction of 1-ethynyl-2-nitrobenzenes
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The reductive hydration of 1-ethynyl-2-nitrobenzenes to the corresponding 2′-aminoacetophenones with a range of common reducing agents is described.
- Bosch, Eric,Jeffries, Laura
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p. 8141 - 8142
(2007/10/03)
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- Discovery of a new stable polymorph of 4-(3-ethynylphenylamino)-6,7-bis(2-methoxyethoxy)quinazolinium methanesulfonate using near-infrared spectroscopy to monitor form change kinetics
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Polymorphism is an important property of crystalline organic molecules, particularly when used to develop medicines. Discovery of all the polymorphs in a series is often difficult. This paper highlights the use of near-infrared spectroscopy to monitor the kinetics of form changes of polymorphs and solvates (hydrates). In the case of mesylate salt 5, this led to the discovery of a new preferred form. Identification and confirmation of unique polymorph crystal states are determined using X-ray powder diffraction patterns. This complements and confirms the kinetic change observed in the near-infrared. The technique is generally applicable to the study of two-phase solid-liquid crystal slurries under isothermal conditions.
- Norris, Timothy,Santafianos, Dinos
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p. 2498 - 2502
(2007/10/03)
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- Synthesis of Some Substituted Dimethyl and Diethyl 4-(Phenylethynyl)-2,6-pyridinedicarboxylates
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Substituted dimethyl and diethyl 4-(phenylethynyl)-2,6-pyridinedicarboxylates were prepared by coupling reactions between dialkyl 4-halo-2,6-pyridinedicarboxylates and terminal arylacetylenes in the presence of an organopalladium catalyst and copper(I) iodide in a suitable solvent system.The terminal acetylenes needed in this work were synthesized from the corresponding aryl halides using either (trimethylsilyl)acetylene or 2-methyl-3-butyn-2-ol followed by deprotection of the triple bond, depending on the nature of the compound in question.
- Takalo, Harri,Kankare, Jouko,Haenninen, Elina
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p. 448 - 454
(2007/10/02)
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- Selective hydrogenation of nitro groups on nitroaromatic acetylenes using an unsupported cobalt polysulfide catalyst
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Aromatic nitroacetylene compounds wherein both the nitro and acetylene groups are directly connected to aromatic ring carbon atoms are hydrogenated at high conversion levels to selectively reduce the nitro function using an unsupported cobalt polysulfide catalyst. Of particular interest is the preparation of aminophenylacetylenes from nitrophenylacetylene.
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- Selective hydrogenation of certain nitroaromatic hydroxy substituted acetylenes over a heterogeneous RuS2 catalyst
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Nitroaromatic hydroxy substituted acetylene compounds wherein both the nitro and acetylene groups are directly connected to aromatic ring carbon atoms are hydrogenated in an inert solvent to selectively reduce the nitro function over a ruthenium disulfide catalyst. Of particular interest is the preparation of aminophenylacetylene from nitrophenyl hydroxy substituted acetylene.
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- Novel substituted amino-aromatic acetylenes and their method of preparation
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Substituted acetylenes wherein the amino and acetylene groups are directly connected to aromatic ring carbon atoms and wherein the substituted acetylene has at least 3 carbon atoms and a hydroxyl group on the carbon atom adjacent to the acetylene group are claimed as new compositions of matter. The new compositions are prepared by the selective reduction of the corresponding nitroaromatic by contacting the nitroaromatic and free molecular hydrogen with a catalyst consisting essentially of ruthenium. A new process is also described for the preparation of an aminophenylacetylene.
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- Process for making nitroarylacetylenes and nitroarylaldehydes
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I have discovered a process for making nitroarylacetylenes and aminoarylacetylenes in which the aryl radical is a phenylene radical or a diphenylene radical. With the exception of p-aminophenylacetylene, the compounds produced by this process are novel. The compounds are all useful as intermediates in the preparation of addition polymers utilizing a polymeric backbone of polyimides. The addition polymers are useful as adhesives and as laminating resins.
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