- Copper-catalyzed oxidative methyl-esterification of 5-hydroxymethylfurfural using TBHP as an oxidizing and methylating reagent: A new approach for the synthesis of furan-2,5-dimethylcarboxylate
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Catalytic conversion of 5-hydroxymethylfurfural (HMF) into furan-2,5-dimethylcarboxylate (FDMC) is of great significance in the production of polyethylene furanoate (PEF), a renewable biomass-derived polymer that can replace the fossil dependent polyethylene terephthalate (PET). Herein, for the first time, we report the synthesis of FDMC from oxidative methyl-esterification of HMF using tert-butyl hydroperoxide (TBHP) as an oxidizing and methylating reagent catalyzed by mesoporous alumina nanospheres-embedded with CuO nanoparticles (CuO/m-Al2O3). The CuO/m-Al2O3 catalysts with different copper contents were prepared by evaporation-induced self-assembly of a structure-directing agent (Pluronic P-123). The decomposition of P-123 during calcination in air results into the formation of a mesoporous structure with highly dispersed CuO nanoparticles. The as-prepared 6-CuO/m-Al2O3 exhibits excellent catalytic activity towards oxidative methyl-esterification of HMF into FDMC with 92% yield and turnover frequency (TOF) of 0.56 h?1. Furthermore, oxidative methyl-esterification of a range of substrates through SP3 C[sbnd]H bond functionalization has also been demonstrated using the same catalyst.
- Gupta, Shyam Sunder R.,Kantam, Mannepalli Lakshmi,Vinu, Ajayan
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p. 259 - 269
(2020/06/27)
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- Method for synthesizing lenvatinib
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The invention belongs to the field of chemical pharmacy, and specifically relates to a method for synthesizing lenvatinib. The method comprises the following steps: step 1, taking 4-aminosalicylic acid as a raw material, and preparing 4-chloro-7-methoxyquinoline-6-formamide through methylation, condensation with meldrum's acid, high-temperature cyclization, chlorination and ammoniation; step 2, taking 3-chloro-4-aminophenol as a raw material, and reacting with phenyl chloroformate and cyclopropylamine to obtain 1-(2-chloro-4-hydroxy phenyl)-3-cyclopropyl urea; and step 3, enabling the 4-chloro-7-methoxyquinoline-6-formamide prepared in step 1 to react with the 1-(2-chloro-4-hydroxy phenyl)-3-cyclopropyl urea prepared in step 2 under action of potassium tert-butoxide to obtain the lenvatinib. The invention provides a brand-new route for synthesising the lenvatinib. The used reagent is cheap and is easily available, is simple in operation, has a yield higher than that of other methods, and is easy for industrial production.
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Paragraph 0022; 0023
(2019/03/28)
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- Synthetic method of anti-cancer drug lenvatinib
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The invention discloses a synthetic method of anti-cancer drug lenvatinib. Lenvatinib is synthesized from the compound p-aminosalicylic acid shown as drawing 1 as a starting material with the method.Reaction conditions are mild, special reaction equipment is not needed, and the applicable range is wider. Raw materials and reagents used in the method are easily purchased from the market, and reduction of production cost is facilitated. The method is simple to operate, short in synthesis period and more suitable for large-scale industrial production of lenvatinib. The method is high in synthesis efficiency, and purity of synthesized lenvatinib is high.
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Paragraph 0112; 0114-0118; 0148-0154; 0185-0190; 0221-0226
(2018/04/02)
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- Synthetic method of 4-amino-5-chloro-2-methoxyl benzoic acid
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The invention discloses a synthetic method of 4-amino-5-chloro-2-methoxyl benzoic acid, wherein the synthetic method includes the steps of dimethyl sulphate methylation, N-chloro-succinimide chlorination, alkaline hydrolysis de-esterification and hydrochloric acid acidification to prepare an intermediate product, wherein aminosalicylic acid, which is low in cost and easy to obtain, is employed as a raw material. The synthetic method is reasonable and simple in process route design, is mild in reaction conditions, is easy to industrially operate, is low in costs of raw material and devices, is high in yield and product quality, and is effectively reduced in production cost.
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Paragraph 0018; 0019; 0020
(2016/10/27)
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- QUINAZOLINE-BASED KINASE INHIBITORS
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The present disclosure is generally directed to compounds which can inhibit AAK1 (adaptor associated kinase 1), compositions comprising such compounds, and methods for inhibiting AAK1.
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Page/Page column 125
(2016/04/26)
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- 2,4-Pyrimidinediamine Compounds and Their Uses
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The present invention provides 2,4-pyrimidinediamine compounds that inhibit the IgE and/or IgG receptor signaling cascades that lead to the release of chemical mediators, intermediates and methods of synthesizing the compounds and methods of using the compounds in a variety of contexts, including in the treatment and prevention of diseases characterized by, caused by or associated with the release of chemical mediators via degranulation and other processes effected by activation of the IgE and/or IgG receptor signaling cascades.
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- ANTIVIRAL COMPOUNDS
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Disclosed herein are new antiviral compounds, together with pharmaceutical compositions that include one or more antiviral compounds, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a paramyxovirus viral infection with one or more small molecule compounds. Examples of paramyxovirus infection include an infection caused by human respiratory syncytial virus (RSV).
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Paragraph 0541
(2015/03/13)
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- ARYL AMIDE KINASE INHIBITORS
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The present disclosure is generally directed to compounds which can inhibit AAK1 (adaptor associated kinase 1), compositions comprising such compounds, and methods for inhibiting AAK1.
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Page/Page column 176
(2015/02/02)
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- Salicylic-acid derivatives as antennae for ratiometric luminescent probes based on lanthanide complexes
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Long-lived ratiometric sensors: Luminescent lanthanide complexes are widely used in time-resolved assays of biomolecules, but most of the sensors with these complexes rely on single-point intensity measurements. Herein, we introduce a simple strategy to create ratiometric probes by using salicylic-acid derivatives as the antenna moiety of Tb3+ complexes. As an example, a probe for alkaline phosphatase (ALP) was developed (see scheme). Copyright
- Terai, Takuya,Ito, Hiroki,Kikuchi, Kazuya,Nagano, Tetsuo
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p. 7377 - 7381
(2012/07/30)
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- AN IMPROVED PROCESS FOR PREPARATION OF AMISULPRIDE
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The present invention is related to a novel process for the preparation of amisulpride (I) which involves : methylation of 4-amino-salicylic-acid (VI) with dimethyl sulphate and base, optionally in presence of TBAB to obtain 4-amino-2-methoxy methyl benzoate (VII) and (ii) oxidation of 4-amino-2-methoxy-5-ethyl thio benzoic acid (IX) or 4-amino-2-methoxy-5- ethyl thio methyl benzoate (X) with oxidizing agent in the presence of sodium tungstate or ammonium molybdate to give 2-methoxy-4-amino-5-ethyl-sulfonyl benzoic acid (IV) or 2- methoxy-4-amino-5-ethyl-sulfonyl methyl benzoate (XI) respectively.
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Page/Page column 10
(2012/01/06)
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- Palladium-catalyzed, modular synthesis of highly functionalized indoles and tryptophans by direct annulation of substituted o-haloanilines and aldehydes
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(Chemical Equation Presented) One-pot synthesis of indoles by a palladium-catalyzed annulation of ortho-haloanilines and aldehydes has been developed. Coupling of ortho-iodoaniline with aldehyde is realized under mild ligandless conditions [Pd(OAc)2, DABCO, DMF, 85°C], whereas X-Phos is found to be the ligand of choice for coupling reactions involving ortho-chloroanilines/ortho-bromoanilines and aldehydes. A variety of orthohaloanilines with different electronic properties are suitable substrates, and aldehydes including chiral ones participated in this reaction without racemization. Coupling of (S)-2-N,N-di-tert-butoxycarbonyl-5-oxopentanoate, derived from L-glutamic acid, with ortho-haloanilines provides a rapid access to the ring-A-substituted tryptophans in good to excellent yields.
- Jia, Yanxing,Zhu, Jieping
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p. 7826 - 7834
(2007/10/03)
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- Indole-type derivatives as inhibitors of p38 kinase
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The invention is directed to methods to inhibit p38-α kinase using compounds comprising a phenyl or thienyl coupled through a piperidine or piperazine nucleus to an indole residue wherein the indole residue mandatorily has a substituent on the ring nitrogen which is an amino or substituted amino group.
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Page/Page column 70
(2008/06/13)
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- 3-CARBOXAMIDE DERIVATIVES OF 5H-PYRROLO[2,1-c][1,4]-BENZODIAZEPINES
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This invention relates to tricyclic non-peptide vasopressin antagonists which are useful in treating conditions where decreased vasopressin levels are desired, such as in congestive heart failure, in disease conditions with excess renal water reabsorption and in conditions with increased vascular resistance and coronary vasoconstriction, the compounds having general structure (I).
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- Synthesis and crystallographic studies of new acridinic esters and amides: An efficient synthetic route to 4-methyl functionalized acridines
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In order to open a new way in antitumor drugs research, an efficient synthetic route to mono functional 4-substitued acridine derivatives has been developed on the basis of direct electrophilic substitution of acridine. This method leads to a wide range of simple acridinic patterns that can be linked to various side chains. We present here the synthesis of two new families of acridine ester and amide derivatives, obtained from acridinic alcohol and amine respectively, with high yields. Some crystallographic aspects of one representative compound of each family are discussed.
- Chiron, Julien,Galy, Jean-Pierre
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p. 1653 - 1672
(2007/10/03)
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- Synthesis and radiolabeling of (S)-4-amino-5-iodo-2-methoxy-N (1- azabicyclo[2.2.2]oct-3-yl)benzamide, the Active enantiomer of [125i]iodozacopride, and re-evaluation of its 5-HT3 receptor affinity
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We report an improved synthesis of unlabeled (S)-iodozacopride, the radiolabeling of (S)-[125I]iodozacopride via deschloro-(S)-zacopride, and a re-evaluation of its affinity for the 5-HT3 receptor. Unlabeled (S)- iodozacopride was prepared in seven steps from 4-aminosalicylic acid via alkaline hydrolysis of its 4-acetamide derivative. Catalytic hydrogenation of (S)-iodozacopride gave deschloro-(S)-zacopride, identical to that obtained from (S)-3-amino-quinuclidine and 4-amino-2-metihoxybenzoic acid via its corresponding 1-imidazole derivative. Radioiodination to produce (S)- [125I]iodozacopride was accomplished by treatment of deschloro-(S)- zacopride with 5mCi sodium 125iodide and chloramine-T in hydrochloric acid. Purification of the reaction products using an HPLC system capable of detecting chlorinated side-products revealed a mixture of 2.1 mCi (1.3nmol) (S)-[125I]iodozacopride and (S)-zacopride (1.5 nmol). Saturation analysis of the binding of the purified (S)-[125I]iodozacopride to whole rat brain homogenates gave an estimated K(D) of 1.10±0.07 nM. As anticipated, this is approximately haft the K(D) reported for binding of racemic [125I]iodozacopride, and differs from the previously reported value by an order of magnitude. Analysis of the apparent binding affinity of a 1: 1 mixture of (S)-[125I]iodozacopride and (S)-zacopride suggests that the previous result may have been confounded by contamination of the product with unlabeled (S)-zacopride. Competition analysis of the displacement of (S)- [125I]iodozacopride binding by unlabeled (S)-iodozacopride and (S)- zacopride gave K(i) values of 0.95 and 0.21 nM, respectively.
- Hewlett, William A.,De Paulis, Tomas,Mason, N. Scott,Schmidt, Dennis E.,Trivedi, Bakula L.,Zhang, Zhang-Jin,Ebert, Michael H.
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p. 2079 - 2084
(2007/10/03)
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- Preparation and in vitro pharmacology of 5-HT4 receptor ligands. Partial agonism and antagonism of metoclopramide analogous benzoic esters
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Alicyclic ester analogues of the gastroprokinetic benzamide metoclopramide (1) and its ester congener SDZ 205557 (2), a 5-HT4 receptor antagonist, were prepared by O-alkylation of 4-amino-5-chloro-2-methoxybenzoate with N-(2-chloroethyl) substituted alicyclic amines. The bromo and iodo analogue of compound 13b (2-(1-piperidinyl)ethyl 4-amino-5-chloro-2-methoxybenzoate) were obtained by halogenation of dechloro-13b with N-halogenated succinimides. The series was evaluated in functional in vitro assays with regard to affinity for serotoninergic 5-HT4, 5-HT3 and muscarinic M3 receptors. The affinities for 5-HT3 and M3 receptors were below 6.0 (pK(B) or pA2). On 5-HT4 receptors in guinea-pig ileal longitudinal muscle and rat oesophagus, the majority of compounds revealed partial 5-HT4 receptor agonism susceptible to blockade by SDZ 205557, a reference 5-HT4 receptor antagonist (pK(B) = 7.25-7.73 (guinea-pig ileum) and 7.09-7.43 (rat oesophagus)). The relative agonist potency was in the range of 5-303% (5-HT: 100%). Compound 13b and its bromo analogue 17 were the most potent esters of the series. The enantiomers of 13g ((R)- and (S)-2-(2-methyl-1-piperidinyl)ethyl 4-amino-5-chloro-2-methoxybenzoate) interacted stereoselectively with 5-HT4 receptors and displayed enantiomeric potency ratios (R)/(S) of 4.3-8.7. There was an excellent correlation between (a) antagonist affinity on guinea-pig ileum and rat oesophagus, (b) relative agonist potency on guinea-pig ileum and rat oesophagus, and (c) between antagonist affinity and relative agonist potency within each assay (r2 > 0.91). The new compounds may serve as academic tools in evaluating the functional role of 5-HT4 receptors. The selective partial 5-HT4 receptor agonists presented in this paper may be useful to restore physiological motility and secretion in the gut with reduced or absent propensity to elicit tachycardia and desensitization of the intestinal target receptor.
- Elz,Keller
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p. 585 - 594
(2007/10/03)
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- Transition Metal Diene Complexes on Organic Synthesis. Part-17. Studies directed towards the Iron-mediated Synthesis of 2-Oxygenated Carbazole Alkaloids
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We described some studies directed towards the synthesis of 2-oxygenated carbazole alkaloids by iron-mediated oxidative coupling of 1,3-cyclohexadiene and the corresponding 3-oxygenated arylamine derivative.The process involves a consecutive formation of a carbon-carbon bond via electrophilic aromatic substitution with an iron-complexed cyclohexadienylium cation and subsequent carbon-nitrogen bond formation via oxidative cyclisation.Using this methodology a synthesis of the biogenetically important alkaloid 2-methoxy-3-methylcarbazole is described.
- Knoelker, Hans-Joachim,Bauermeister, Michael
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p. 345 - 354
(2007/10/02)
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