- A novel method for synthesis of flutamide on the bench-scale
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Flutamide has been synthesised conveniently in high yields and by an economically beneficial method. Benzotrifluoride was first nitrated and the product was reduced and acylated in one pot in the presence of iron powder and isobutyric acid to produce 3-trifluoroisobutyranilide. Finally, flutamide was produced by further nitration.
- Ghaffarzadeh, Mohammad,Rahbar, Sahar
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- A Nickel(II)-Mediated Thiocarbonylation Strategy for Carbon Isotope Labeling of Aliphatic Carboxamides
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A series of pharmaceutically relevant small molecules and biopharmaceuticals bearing aliphatic carboxamides have been successfully labeled with carbon-13. Key to the success of this novel carbon isotope labeling technique is the observation that 13C-labeled NiII-acyl complexes, formed from a 13CO insertion step with NiII-alkyl intermediates, rapidly react in less than one minute with 2,2’-dipyridyl disulfide to quantitatively form the corresponding 2-pyridyl thioesters. Either the use of 13C-SilaCOgen or 13C-COgen allows for the stoichiometric addition of isotopically labeled carbon monoxide. Subsequent one-pot acylation of a series of structurally diverse amines provides the desired 13C-labeled carboxamides in good yields. A single electron transfer pathway is proposed between the NiII-acyl complexes and the disulfide providing a reactive NiIII-acyl sulfide intermediate, which rapidly undergoes reductive elimination to the desired thioester. By further optimization of the reaction parameters, reaction times down to only 11 min were identified, opening up the possibility of exploring this chemistry for carbon-11 isotope labeling. Finally, this isotope labeling strategy could be adapted to the synthesis of 13C-labeled liraglutide and insulin degludec, representing two antidiabetic drugs.
- Pedersen, Simon S.,Donslund, Aske S.,Mikkelsen, Jesper H.,Bakholm, Oskar S.,Papp, Florian,Jensen, Kim B.,Gustafsson, Magnus B. F.,Skrydstrup, Troels
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- 3-(Ethoxycarbonyl)-1-(5-methyl-5-(nitrosooxy)hexyl)pyridin-1-ium cation: A green alternative to tert-butyl nitrite for synthesis of nitro-group-containing arenes and drugs at room temperature
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Due to their remarkable properties, task-specific ionic liquids have turned out to be progressively popular over the last few years in the field of green organic synthesis. Herein, for the first time, we report that a new task-specific nitrite-based ionic liquid such as 3-(ethoxycarbonyl)-1-(5-methyl-5-(nitrosooxy)hexyl)pyridin-1-ium bis(trifluoromethanesulfonyl)imides (TS-N-IL) derived from biodegradable ethyl nicotinate indeed acted as an efficient and eco-friendly reagent for the synthesis of highly valuable nitroaromatic compounds and drugs including nitroxynil, tolcapone, niclofolan, flutamide, niclosamide and nitrazepam. The bridging of an ionic liquid with nitrite group not only increases the yield and rate of direct C[sbnd]N bond formation reaction but also allows easy product separation and recyclability of a byproduct. Nonvolatile nature, easy synthesis, merely stoichiometric need and mildness are a portion of the extra focal points of TS-N-IL while contrasted with tert-butyl nitrite an outstanding and highly-flammable reagent utilized largely in organic synthesis.
- Chaudhary, Renu,Natarajan, Palani,Rani, Neetu,Sakshi,Venugopalan, Paloth
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supporting information
(2019/12/30)
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- Synthesis method of drug intermediate flutamide
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The invention discloses a synthesis method of a drug intermediate flutamide. N-hexane, m-trifluoromethylaniline, isobutyric anhydride, NaOH, m-isobutyramidobenzotrifluoride, sodium hydrogen carbonateand ethyl orthosilicate are used as main raw materials; a method of combining a sol-gel method with calcination is utilized; SiO2 is used as a carrier; a perfluorosulfonic resin solution is directly dispersed on a porous SiO2 colloid serving as a skeleton; a mixing-ratio relation among raw materials is strictly explored; a catalyst for preparing the flutamide from the isobutyric anhydride, which has certain crystal form, grain size, pore structure and specific area and high mechanical strength is developed; the raw materials used by the synthesis method are according to the following mixing ratios in which a mass ratio of the isobutyric anhydride to the m-trifluoromethylaniline is 2 to 1, a volume ratio of the n-hexane to the NaOH is 2 to 1, and the volume ratio of concentrated sulfuric acid to concentrated nitric acid is 10 to 1; a preparation method of the flutamide has the characteristics of simpleness, easiness, feasibleness, short preparation period and the like, and the raw materials and the catalyst which are used in a technical process have high efficiency, wide application ranges and an excellent catalytic effect on the preparation of the flutamide from the isobutyric anhydride, are simple, convenient, quick and extremely environment-friendly, moreover, are easily recovered and can be regenerated.
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Paragraph 0008; 0010-0028
(2018/06/21)
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- TCDA: Practical Synthesis and Application in the Trifluoromethylation of Arenes and Heteroarenes
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A practical synthesis of the reagent trimethylsilyl chlorodifluoroacetate (TCDA) is reported on 50 g scale. The trifluoromethylation with TCDA was optimized, and the reaction shows very broad scope with respect to electron-deficient, -neutral, -rich aryl/heteroaryl iodides, as well as excellent functional group tolerability, such as ester, amide, aldehyde, hydroxyl, and carboxylic acid. The reagent was also applied to the late-stage trifluoromethylation of three medicinally relevant compounds. Additionally, the building block trifluoromethylpyridine and one drug related molecule Boc-Fluoxetin were synthesized in 10 g scale by this method, demonstrating its practical applications in process chemistry.
- Wang, Jian,Zhang, Xiaomin,Wan, Zehong,Ren, Feng
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p. 836 - 839
(2016/05/19)
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- Palladium-Catalyzed Synthesis of Aryl Amides through Silanoate-Mediated Hydrolysis of Nitriles
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A procedure for the formation of aryl amides through the palladium-catalyzed coupling of nitriles and aryl bromides, via the formation of intermediary silanoate derived imidate species is reported. Optimization was undertaken and examples of the process are described that furnish the products in up to 86% isolated yield.
- McPherson, Christopher G.,Livingstone, Keith,Jamieson, Craig,Simpson, Iain
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supporting information
p. 88 - 92
(2015/12/26)
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- Mild and Efficient Cobalt-Catalyzed Cross-Coupling of Aliphatic Amides and Aryl Iodides in Water
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A convenient protocol for the C-N cross-coupling of aliphatic amides and iodobenzene is demonstrated using a simple and inexpensive Co(C2O4)·2H2O/N,N′-dimethylethylenediamine (DMEDA) catalytic system in water. Good yields of N-arylated products were isolated (up to 85%) and the protocol has been successfully applied to the synthesis of the anticancer drug, flutamide.
- Tan, Bryan Yong-Hao,Teo, Yong-Chua
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supporting information
p. 1697 - 1701
(2015/07/20)
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- An azobenzene-containing metal-organic framework as an efficient heterogeneous catalyst for direct amidation of benzoic acids: Synthesis of bioactive compounds
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An azobenzene-containing zirconium metal-organic framework was demonstrated to be an effective heterogeneous catalyst for the direct amidation of benzoic acids in tetrahydrofuran at 70°C. This finding was applied to the synthesis of several important, representative bioactive compounds.
- Hoang, Linh T. M.,Ngo, Long H.,Nguyen, Ha L.,Nguyen, Hanh T. H.,Nguyen, Chung K.,Nguyen, Binh T.,Ton, Quang T.,Nguyen, Hong K. D.,Cordova, Kyle E.,Truong, Thanh
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supporting information
p. 17132 - 17135
(2015/12/04)
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- PRODUCTION OF RED BLOOD CELLS AND PLATELETS FROM STEM CELLS
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This disclosure provides methods of making a megakaryocyte-erythroid progenitor cell (MEP), comprising differentiating a stem cell into a MEP in culture in the presence of an aryl hydrocarbon receptor (AhR) agonist. In some embodiments the stem cell is a pluripotent stem cell. In some embodiments the MEP co-expresses CD41 and CD235. In some embodiments the number of MEPs produced in the culture increases exponentially. Methods of making a red blood cell (RBC) by culturing a MEP in the presence of an AhR agonist are also provided. Methods of making a megakaryocyte and/or a platelet, comprising culturing a MEP in the presence of an AhR modulator are also provided. In some embodiments the AhR modulator is an AhR antagonist. This disclosure also provides compositions comprising at least 1 million MEPs per ml and compositions in which at least 50% of the cells are MEPs.
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- THERAPEUTIC FOR HEPATIC CANCER
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A novel pharmaceutical composition for treating or preventing hepatocellular carcinoma and a method of treatment are provided. A pharmaceutical composition for treating or preventing liver cancer is obtained by combining a chemotherapeutic agent with an anti-glypican 3 antibody. Also disclosed is a pharmaceutical composition for treating or preventing liver cancer which comprises as an active ingredient an anti-glypican 3 antibody for use in combination with a chemotherapeutic agent, or which comprises as an active ingredient a chemotherapeutic agent for use in combination with an anti-glypican 3 antibody. Using the chemotherapeutic agent and the anti-glypican 3 antibody in combination yields better therapeutic effects than using the chemotherapeutic agent alone, and mitigates side effects that arise from liver cancer treatment with the chemotherapeutic agent.
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- Anti-Claudin 3 Monoclonal Antibody and Treatment and Diagnosis of Cancer Using the Same
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Monoclonal antibodies that bind specifically to Claudin 3 expressed on cell surface are provided. The antibodies of the present invention are useful for diagnosis of cancers that have enhanced expression of Claudin 3, such as ovarian cancer, prostate cancer, breast cancer, uterine cancer, liver cancer, lung cancer, pancreatic cancer, stomach cancer, bladder cancer, and colon cancer. The present invention provides monoclonal antibodies showing cytotoxic effects against cells of these cancers. Methods for inducing cell injury in Claudin 3-expressing cells and methods for suppressing proliferation of Claudin 3-expressing cells by contacting Claudin 3-expressing cells with a Claudin 3-binding antibody are disclosed. The present application also discloses methods for diagnosis or treatment of cancers.
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- Novel and gram-scale green synthesis of flutamide
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Isobutyric acid in the presence of cyanuric chloride and N-methylmorpholine was converted into active ester 3 at 0-5°C, and it was subsequently treated with 3-aminobenzotrifluoride 4 at 25°C to furnish corresponding amide 5. This amide finally, on nitration, produced the desired product flutamide, 2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]propionamide 6 in good yield. By-product 2,4,6-trihydroxy-1,3,5-triazine 7 was converted into the useful starting material cyanuric chloride 1 by refluxing with N,N-diethylamine and POCl3. Copyright Taylor & Francis Group, LLC.
- Bandgar,Sawant
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p. 859 - 864
(2007/10/03)
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- Process for the production of dry pharmaceutical forms and the thus obtained pharmaceutical compositions
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A process for the production of a solid dispersion of at least one therapeutic agent in a hydrophilic carrier having enhanced solubility in an aqueous media comprising dissolving at least one therapeutic agent in a volatile organic solvent containing a very hydrophilic polymer and evaporating the solvent to dryness; to form a co-precipitate of therapeutic agent and hydrophilic polymer. This invention relates to the resulting products and to their therapeutic method of use.
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- Process for the production of dry pharmaceutical forms and the thus obtained pharmaceutical compositions
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A process for the production of a solid dispersion of at least one therapeutic agent in a hydrophilic carrier having enhanced solubility in an aqueous media comprising dissolving at least one therapeutic agent in a volatile organic solvent containing a very hydrophilic polymer and evaporating the solvent to dryness to form a co-precipitate of therapeutic agent and hydrophilic polymer and the resulting products and their therapeutic method of use.
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- Combination with anti-hormonal compounds and binding molecules for the treatment of cancer
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The invention refers to a combination comprising an anti-hormonal compound and a binding molecule specifically binding a c-erb B-2 protein wherein the binding molecule may induce inhibition of tumor cell proliferation., The combination of the invention may be used as medicament for a therapeutic application for treating cancer, wherein the anti-hormonal compound and the binding molecule are administered simultaneously, separately or sequentially.
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- Process for nitrating anilides
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This invention describes a novel process whereby meta-substituted anilides are nitrated in the para position in high yields.
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- Substituted anilides as anti-androgens
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This application relates to certain 4'-substituted and to 3',4'-disubstituted anilides, to methods for their preparation and to methods for their use as anti-androgens.
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- Antiandrogenic agents and method for the treatment of androgen dependent disease states
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This application relates to certain 4''-substituted and to 3'',4''-disubstituted anilides, to methods for their preparation and to methods for their use as antiandrogens. These substituted anilides are useful in the treatment of androgen dependent disease states, such as benign prostatic hypertrophy, hirsutism, acne and the like.
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