- A 1H NMR and molecular modelling investigation of diastereotopic methylene hydrogen atoms
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The 1H NMR spectra of methyl 3-bromo-2-methylpropionate (1a) and the corresponding chloro compound (2a) show no long-range coupling between the methyl and methylene protons. In contrast, in the analogous dihalocompounds, methyl 2,3-dibromo-2-methylpropionate (1b) and methyl 2,3-dichloro-2-methylpropionate (2b), one of the methylene protons exhibits a large 4JHH coupling (0.8 Hz) to the methyl group, but the other proton shows no observable splitting. This can be explained quantitatively by calculations of the conformational preferences in these compounds combined with the known orientation dependence of the 4JHH couplings. One conformer predominates in the dihalo compounds 1b and 2b, and this is responsible for the 4JHH coupling. In 1a and 2a all three conformers are populated and the 4JHH couplings average to zero. The technique is a potentially general method of unambiguously assigning diastereotopic methylene protons. Copyright
- Tormena, Claudio F.,Freitas, Matheus P.,Rittner, Roberto,Abraham, Raymond J.
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Read Online
- Photoinduced Fe-Based Atom Transfer Radical Polymerization in the Absence of Additional Ligands, Reducing Agents, and Radical Initiators
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A photoinduced atom transfer radical polymerization (ATRP) of methacrylate with a Fe-based catalytic system was studied in the absence of additional ligands, reducing agents, and radical initiators. Linear semilogarithmic polymerization kinetics and narrow molecular weight distributions were obtained in the presence but also absence of conventional ATRP initiators. The proposed mechanism involves monomer-mediated photoreduction of Fe(III) to Fe(II) but also photoactivation of Fe(II) species. The polymerization was studied with different radiation sources for several methacrylates. The technique was successfully used to synthesize block copolymers, confirming the living nature of ATRP.
- Pan, Xiangcheng,Malhotra, Nikhil,Zhang, Jianan,Matyjaszewski, Krzysztof
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Read Online
- A paraquat emetic and preparation method
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The invention relates to the field of organic synthetic technology, in particular to a paraquat emetic and preparation method, comprises the following preparation steps, S1, preparation of [...]; S2, the preparation of the etherification; S3, pyrimidine triazole; S4, PP796 preparation. The invention one-pot method for directly simple high yield of synthetic method is more suitable for industrial production technology, the process route and is simple, low cost, production and operation method is simple and convenient, high yield, the total yield to methacrylic acid methyl ester idea can reach 43.5% or more, the obtained product and luster is pure white, crystalline state is good, content ≥ 99%.
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Paragraph 0018-0040; 0042
(2019/04/04)
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- A preparation method of the emetic (by machine translation)
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The invention relates to the field of organic synthetic technology, in particular to a emetic preparation method, comprises the following steps: S1, 3 - methoxy methyl acrylic acid methyl ester preparation; S2, synthesis of [...]; S3, is the synthesis of third zuo; S4, and aldehyde; S5, closed-loop. This invention adopts the single melamine as the synthetic starting material, greatly reducing the cost, dicyandiamide as to effectively solve the problem of lack of raw material sources; solved in the prior art long reaction time, the reaction condition is sensitive, harsh, side reaction are numerous and complex, the use of expensive or difficult to prepare sodium of other reagents, reactions caused low overall yield, the product quality is poor, so that the synthesis process technology of the route is more stable, good reproducibility, high yield, the product quality is good, content can be up to 99.5%, the yield can reach 85.6%, has higher economic benefits. (by machine translation)
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Paragraph 0026; 0031; 0036; 0042; 0047; 0051; 0052; 0058
(2019/04/17)
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- Technology for three-innovation synthesis of 2-amino-5-methyl-4-oxo-3-n-propyltriazolopyrimidine
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The invention discloses a technology for synthesizing 2-amino-5-methyl-4-oxo-3-n-propyl-6H-triazolo-[1,5-a]pyrimidine. Methyl methacrylate and bromine are firstly subjected to an addition reaction toprepare methyl 2,3-dibromo-2-methylpropanoate, and then the methyl 2,3-dibromo-2-methylpropanoate and sodium methylate are etherified in a new suitable solvent to prepare methyl 3,3-dimethoxy-2-methylpropionate etherate; the etherate and 3,5-diamino-1,2,4-triazole, prepared from hydrazine hydrate and dicyandiamide under the catalysis of an acid, are condensed at an intermediate temperature of about 115 DEG C under the catalysis of an organic base to obtain a pyrimidotriazole compound; and the pyrimidotriazole material liquid and 1-chloropropane undergo a direct alkylation reaction in an inorganic or organic bas and a new solvent to obtain the 2-amino-5-methyl-4-oxo-3-n-propyl-6H-triazolo-[1,5-a]pyrimidine. The technology is improved by the three major innovations of improving the catalyticsynthesis conditions of the condensation ring closure of the pyrimidotriazole, optimizing the alkylation substitution reaction and the process technology of the pyrimidinetriazole and innovating theraw material of an alkylation reagent, so the technology has the advantages of great improvement of the yield, simplicity in operation, mild reaction conditions, and safety to devices and human bodies, the total yield of methyl methacrylate can reach 46.5% or above, and the obtained product has a white color and a good crystalline state, and has a content of 99% or more.
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Paragraph 0015; 0029-0040
(2019/11/29)
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- Discovery of a novel series of pyrazolo[1,5-a]pyrimidine-based phosphodiesterase 2A inhibitors structurally different from N-((1S)-1-(3-fluoro-4-(trifluoromethoxy)phenyl)-2-methoxyethyl)-7-methoxy-2-oxo-2,3-dihydropyrido[2,3-b]pyrazine-4(1H)-carboxamide (TAK-915), for the treatment of cognitive disorders
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It has been hypothesized that selective inhibition of phosphodiesterase (PDE) 2A could potentially be a novel approach to treat cognitive impairment in neuropsychiatric and neurodegenerative disorders through augmentation of cyclic nucleotide signaling pathways in brain regions associated with learning and memory. Following our earlier work, this article describes a drug design strategy for a new series of lead compounds structurally distinct from our clinical candidate 2 (TAK-915), and subsequent medicinal chemistry efforts to optimize potency, selectivity over other PDE families, and other preclinical properties including in vitro phototoxicity and in vivo rat plasma clearance. These efforts resulted in the discovery of N-((1S)-2-hydroxy-2-methyl-1-(4-(trifluoromethoxy)phenyl)propyl)-6-methyl-5-(3-methyl-1H-1,2,4triazol-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (20), which robustly increased 3′,5′-cyclic guanosine monophosphate (cGMP) levels in the rat brain following an oral dose, and moreover, attenuated MK-801-induced episodic memory deficits in a passive avoidance task in rats. These data provide further support to the potential therapeutic utility of PDE2A inhibitors in enhancing cognitive performance.
- Mikami, Satoshi,Kawasaki, Masanori,Ikeda, Shuhei,Negoro, Nobuyuki,Nakamura, Shinji,Nomura, Izumi,Ashizawa, Tomoko,Kokubo, Hironori,Hoffman, Isaac Dylan,Zou, Hua,Oki, Hideyuki,Uchiyama, Noriko,Hiura, Yuuto,Miyamoto, Maki,Itou, Yuuki,Nakashima, Masato,Iwashita, Hiroki,Taniguchi, Takahiko
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p. 1058 - 1077
(2017/11/17)
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- HETEROCYCLIC COMPOUND
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A compound represented by the formula (I): wherein each symbol is as described in the SPECIFICATION, or a salt thereof has a PDE2A inhibitory action, and is useful as a prophylactic or therapeutic drug for schizophrenia, Alzheimer's disease and the like.
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Paragraph 1444; 1658
(2016/06/28)
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- Heterocyclic compound
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A compound represented by the formula (I): wherein each symbol is as described in the SPECIFICATION, or a salt thereof has a PDE2A inhibitory action, and is useful as a prophylactic or therapeutic drug for schizophrenia, Alzheimer’s disease and the like.
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Paragraph 0183
(2017/02/24)
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- Highly enantioselective Rh-Catalyzed Alkenylation of imines: Synthesis of Chiral Allylic Amines via Asymmetric addition of Potassium Alkenyltrifluoroborates to N-Tosyl imines
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For the first time, simple N-tosyl aryl aldimines, prepared from the condensation of tosyl amide and aromatic aldehydes, can be used as substrates in the rhodium catalyzed 1,2- addition reaction using alkenylboron nucleophiles. In the presence of 1.5 mol % of [RhCl(1e)]2, enantioselective addition of various potassium alkenyltrifluoroborates to aryl aldimines furnished the corresponding chiral allylic amines in 73-96% yield and 72->99.5% ee. Notably, this method efficiently provides the di-, tri-, and tetrasubstituted allylic N-tosyl amines with high asymmetric induction.
- Gopula, Balraj,Chiang, Chien-Wei,Lee, Way-Zen,Kuo, Ting-Shen,Wu, Ping-Yu,Henschke, Julian P.,Wu, Hsyueh-Liang
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supporting information
p. 632 - 635
(2014/04/03)
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- Catalytic enantioselective nazarov cyclization: Construction of vicinal all-carbon-atom quaternary stereocenters
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The diastereoselective asymmetric synthesis of vicinal all-carbon-atom quaternary stereocenters is a challenging problem in organic synthesis for which only few solutions have been described. A catalytic asymmetric Nazarov cyclization of fully substituted dienones that provides cyclopentenone derivatives with vicinal quaternary stereocenters in high optical purity and as single diastereoisomers is now reported.
- Jolit, Anais,Walleser, Patrick M.,Yap, Glenn P. A.,Tius, Marcus A.
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supporting information
p. 6180 - 6183
(2014/06/23)
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- An approach to aminonaphthoquinone ansamycins using a modified Danishefsky diene
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A robust and scalable synthesis of a novel, cyano-substituted Danishefsky-type diene and its use in the Diels-Alder reaction with various dienophiles is reported. The diene allows for the rapid construction of highly substituted aminonaphthoquinones that occur in numerous ansamycin antibiotics.
- Kuttruff, Christian A.,Geiger, Simon,Cakmak, Mesut,Mayer, Peter,Trauner, Dirk
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supporting information; experimental part
p. 1070 - 1073
(2012/04/04)
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- Gram-scale synthesis of iejimalide B
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IejimalideB (2) is the most promising member of a small family of marine polyene macrolides endowed with remarkably selective activity against human cancer cell lines. As this product, however, is hardly available from the natural sources, a detailed evaluation requires the development of an efficient and practical synthetic approach. This challenge has now been met by adapting the first total synthesis of 2 previously reported by our group to the needs of high material throughput. Redesigning the access routes to the five required building blocks in combination with a careful optimization of the fragment coupling processes provided gram amounts of this valuable compound in a sequence of no more than 16 linear steps with an overall yield of about 7 %. Key elements of the successful strategy include: i) three hydrostannylation processes of elaborate terminal alkynes with "lower order" stannyl cuprates, ii) a Brown allylation, a Noyori transfer hydrogenation, and a Marshall propargylation to set the chiral centers at C9, C17, C22 and C23, and iii) a modified Takai-Utimoto olefination for the preparation of the very labile skipped 1,4-diene flanking the ester group. The assembly process benefited from a particularly mild protocol for the Stille cross-coupling previously developed in this laboratory, which clearly outperformed the alternative Suzuki reaction in terms of yield and scalability. The 24-membered macrocyclic frame was forged by a remarkably selective ring-closing metathesis reaction (RCM), in which two out of the ten double bonds present in the cyclization precursor were selectively activated with the aid of a second-generation Grubbs catalyst. Copyright
- Gagnepain, Julien,Moulin, Emilie,Fuerstner, Alois
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supporting information; experimental part
p. 6964 - 6972
(2011/07/30)
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- An improved synthesis of (-)-brevisamide, a marine monocyclic ether amide of dinoflagellate origin
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An improved synthesis of (-)-brevisamide a marine cyclic ether isolated from the red-tide dinoflagellate Karenia brevis was achieved. The ether ring portion was constructed from an unsaturated lactone, which was prepared enantioselectively via an Evans aldol reaction and one-pot lactonization in the presence of excessive base after an Ando reaction. The ether ring and a dienol side chain fragment were connected via Suzuki-Miyaura coupling.
- Tsutsumi, Ryosuke,Kuranaga, Takefumi,Wright, Jeffrey L.C.,Baden, Daniel G.,Ito, Emiko,Satake, Masayuki,Tachibana, Kazuo
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experimental part
p. 6775 - 6782
(2010/10/02)
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- IspH protein of the deoxyxylulose phosphate pathway: Mechanistic studies with C1-deuterium-labeled substrate and fluorinated analogue
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(Chemical Equation Presented) The last step of the deoxylxylulose phosphate pathway is catalyzed by IspH to synthesize two precursors for isoprenoid biosynthesis. The lack of a primary kinetic isotope effect at C1 and enzymatic evaluation with a fluorinated analogue (see scheme) suggest that the C1-position is not involved in the IspH-catalyzed reaction. FldA = flavodoxin, Fpr = flavodoxin reductase, NADPH = nicotinamide adenine dinucleotide phosphate, PPi = P2O63-.
- Xiao, Youli,Liu, Pinghua
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supporting information; experimental part
p. 9722 - 9725
(2009/05/30)
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- Enantioselective synthesis of a trans-7,8-dimethoxycalamenene
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trans-7,8-Dimethoxy-11,12-dehydrocalamenene, a projected intermediate for the total synthesis of marine serrulatane and amphilectane diterpenes, was efficiently synthesized. Starting from a styrene, asymmetric Rh-catalyzed hydroboration using a novel chiral P.P-bidentate ligand afforded an organoboron intermediate (93% ee) which was directly used for C-C bond formation (double homologation, Suzuki coupling). The 1,4-trans-disubstituted tetralin skeleton was selectively formed by a Friedel-Crafts-type catlonic cyclization under strictly aprotic conditions (Me2AlCl) to suppress a remarkable proton-catalyzed disproportionation via diastereoselective hydride transfer.
- Werle, Susen,Fey, Thorsten,Neudoerfl, Joerg M.,Schmalz, Hans-Guenther
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p. 3555 - 3558
(2008/02/12)
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- Phosphinate, sulfonate, and sulfonamidate dipeptides as potential inhibitors of Escherichia coli aminopeptidase N
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In an effort to prepare novel inhibitors of bacterial aminopeptidase N (PepN), the phosphinate, propenylphosphinate, decylphosphinate, sulfonate, and sulfonamidate analogs of Ala-Ala were synthesized and tested as inhibitors. Phosphinate 1 was shown to inhibit PepN with a Ki of 10 μM, and propenylphosphinate 2 and decylphosphinate 3 inhibited PepN with a Ki of ca. 1 μM. Sulfonate and sulfonamidate analogs did not inhibit PepN.
- Yang, Ke-Wu,Golich, Frank C.,Sigdel, Tara K.,Crowder, Michael W.
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p. 5150 - 5153
(2007/10/03)
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- Process for preparing beta-L-2'deoxy-thymidine
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The present invention relates to a new, essentially four-step process for preparing beta-L-2′-deoxy-thymidine starting from L-arabinose. The process according to the invention is particularly important for mass production of beta-L-2′-deoxy-thymidine.
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- Synthesis of racemic carbocyclic cyclopropanoid nucleoside analogues
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As further representatives of a novel class of carbocyclic nucleoside analogues (±)-cis- and (±)-trans-(2-hydroxymethylcyclopropyl)-uracil, -thymine, and -inosine were synthesized from the corresponding dialkyl 1,2-cyclopropane dicarboxylates.
- Csuk, Rene,Von Scholz, Yvonne
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p. 7193 - 7206
(2007/10/02)
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- REACTIONS OF HALOGEN FLUORIDES XII. REACTION OF BROMINE TRIFLUORIDE WITH BROMINE-CONTAINING ESTERS. A NEW METHOD FOR THE SYNTHESIS OF FLUOROALKYL 2-FLUOROACRYLATES
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Being weak Lewis bases, esters reduce the reactivity of bromine trifluoride in the substitutive fluorination of organic bromine derivatives.For this reason the rate of the reaction of bromine trifluoride with bromine-containing esters depends not only on the electronic characteristics of the substituents at the reaction center but also on the basicity of the ester.As a rule, the selectivity of the reaction increases with increase in the basicity of the ester.The reaction of bromine trifluoride or chlorine monofluoride with fluoroalkyl 2,3-dibromopropionates can be used successfully for the synthesis of monomers (fluoroalkyl 2-fluoroacrylates).
- Kartashov, A. V.,Chuvatkin, N. N.,Boguslavskaya, L. S.
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p. 2243 - 2248
(2007/10/02)
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- Process for the production of O 2,2'-anhydro-1-(β-D-arabinofuranosyl)thymine
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In the disclosed process, an O2, 2' anhydro-1-(β-D-arabinofuranosyl)thymine is formed by condensing a 2-amino-β-arabinofurano[1',2':4,5,]-2-oxazoline with a compound of the formula STR1 wherein R1 is C1 -C4 alkyl; X is halogen or OR2, wherein R2 is H, C1 -C4 alkyl or phenyl; in the presence of a suitable solvent at about 0° C. to about 150° C. Catalytic agents such as dimethylaminopyridine and triethylamine may also be added to accelerate the reaction. Protected intermediates of the anhydronucleosides and aminooxazolines are also disclosed.
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- Organic compounds and their use as pharmaceuticals
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A pharmaceutically-active compound of the formula STR1 in which R1 is C1-4 alkythio, C1-4 alkylsulphinyl or C1-4 alkylsulphonyl, R2 is C1-4 alkyl, R3 is C1-4 alkyl or C2-4 alkenyl, and X is (i) --(CH2)n N(R4)2 where each R4 independently is C1-4 alkyl, C2-4 alkenyl or optionally substituted C6 H5 CH2 --, and n is 1, 2 or 3, or (ii) a 5- to 8-membered alicyclic group containing one or two nitrogen atoms and directly attached to the amido nitrogen or attached by a C1-3 alkylene chain; and salts thereof.
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- An Improved Synthesis of 3-(1-Imidazolyl)-2-alkenoic Acid Derivatives and Related Compounds
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The preparative method of 3-(1-imidazolyl)-2-alkenoic acid derivatives and the related compounds was improved by the use of strong bases such as sodium hydride in DMF.By this improved method, the preparation of 2-substituted 3-(1-imidazolyl)-2-alkenoic acid derivatives was accomplished in good yields.
- Kashima, Choji,Yoshiwara, Nobutoshi,Tajima, Tadakuni,Omote, Yoshimori
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p. 1595 - 1596
(2007/10/02)
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- Kinetics and Mechanism of Bromine Addition to Derivatives of Unsaturated Aliphatic Carboxylic Acids in Aqueous Solution
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This paper deals with the kinetics of bromine addition to unsaturated compounds in presence of added bromide ions at 22, 30, 38, 46, and 54 deg C.The substrates used were acrylamide (AAm), methyl acrylate (MA), ethyl acrylate (EA), butyl acrylate (BA), t-butyl acrylate (tBA), methacrylamide (MAAm), methyl methacrylate (MMA), ethyl methacrylate (EMA), methyl crotonate (MC), and ethyl crotonate (EC).The kinetics was followed potentiometrically.The activation parameters (ΔH*, ΔS*, and ΔG*) were calculated and compared.Estimation of product ratio of bromohydrin to dibromide showed the absence of any correlation of the product formation with reactivity of the substrates.The observed parameters are discussed in relation to the proposed reaction mechanisms.
- Mohamed Farook, Syed Ahamed,Viswanathan, Seshaiyer,Ganesan, Ramachandran
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p. 1394 - 1400
(2007/10/02)
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- Carbocyclic Analogs of Thymine Nucleosides and Related 1-Substituted Thymines
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The carbocyclic analogs of thymidine (IXf), 1-β-ribofuranosylthymine (IXg), and 1-β-3'-deoxyribofuranosylthymine (IXe) were synthesized by incorporating modifications into the Shaw method of synthesizing 2,4-(1H,3H)pyrimidinediones via acryloylureas.Simpler analogs of thymine nucleosides were also prepared by this method.The carbocyclic analog of thymidine displayed modest activity against Leukemia L1210 in vivo.It differs from a compound prepared previously by a Prins reaction.
- Shealy, Y.Fulmer,O'Dell, C.Allen,Thorpe, Martha C.
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p. 383 - 389
(2007/10/02)
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