- A preparation method of the peculiar smell impurity
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A disclosed preparation method for a vildagliptin impurity comprises the following steps: (1) reacting methyl L-prolinate with chloroacetyl chloride under an alkali condition to generate a compound I; (2) performing condensation reaction on the compound 1 and 3-amino-1-hydroxyadamantane to generate a compound 2; and (3) performing a self condensation reaction on the compound 2 under an alkali condition to obtain vildagliptin related compound 2. According to the vildagliptin related compound 2 synthetic method, methyl L-prolinate is taken as the raw material and is reacted with chloroacetyl chloride under the alkali condition for preparing the compound 1, the compound 1 is condensed with 3-amino-1-hydroxyadamantane for generating the compound 2, and the compound 2 is subjected to the self condensation reaction under the alkali condition for obtaining the vildagliptin related compound 2. The synthetic method is simple, reaction conditions are mild, operationality is high, a product according with quality standard is obtained through simple purification, and research and development cost is effectively reduced.
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Paragraph 0034; 0035
(2017/09/26)
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- Carbostyril carboxylic compounds and intermediates, preparation method and application thereof
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The invention discloses carbostyril carboxylic compounds and hydrochlorides thereof and also discloses a preparation method of the compounds and the hydrochlorides thereof as well as an application of the compounds and the hydrochlorides thereof in preparing gram-positive bacterium-preventing or gram-negative bacterium-preventing drugs. Moreover, the invention discloses intermediates for preparing the compounds and a preparation method of the intermediates.
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Paragraph 0185; 0187
(2017/07/12)
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- NOVEL ECONOMIC PROCESS FOR VILDAGLIPTIN
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The present invention relates to a commercially viable novel process for manufacturing Vildagliptin in high yield with high chemical and chiral purity.
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Page/Page column 17-18
(2015/09/28)
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- Synthesis of 2-pyridones by cycloreversion of [2.2.2]- bicycloalkene diketopiperazines
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A general strategy for the conversion of [2.2.2]-diazabicyclic alkene structures to 2-pyridone aromatic heterocyclic products is reported. The reaction sequence starts from 2,5-diketopiperazine (DKP) derivatives, is compatible with both aromatic and aliphatic aldehyde components, and can intercept either intra- or intermolecular cycloaddition manifolds. Priming of one aza-bridging function in the intermediate [2.2.2]-DKP scaffold permits cycloreversion (microwave heating) and selective extrusion of cyanate derivatives leading to the formation of 2-pyridone structures. Progress toward the synthesis of louisianin A and B, antiproliferative 2-pyridone natural products, is also disclosed.
- Margrey, Kaila A.,Hazzard, Amy D.,Scheerer, Jonathan R.
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supporting information
p. 904 - 907
(2014/03/21)
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- Enantioselective synthesis of (+)-malbrancheamide B
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The asymmetric total synthesis of the chlorinated [2.2.2]-diazabicyclic indole alkaloid (+)-malbrancheamide B is reported. Key to the synthesis is a domino reaction sequence that employs an aldol condensation, alkene isomerization, and intramolecular Diels-Alder cycloaddition. Diastereofacial selection between the azadiene stereofaces is enforced with a chiral aminal auxiliary. A formal 7-step (longest linear route) synthesis of (±)-malbrancheamide B is also reported.
- Laws, Stephen W.,Scheerer, Jonathan R.
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p. 2422 - 2429
(2013/05/08)
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- SYNTHESIS OF [2.2.2]-DIAZABICYCLIC RING SYSTEMS
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Herein we describe compositions and methods for the synthesis of [2.2.2]-diazabicyclic structures comprising a domino reaction sequence involving aldol condensation, alkene isomerization, and intramolecular hetero-Diels-Alder cycloaddition. Excellent diastereofacial control during the cycloaddition is enforced with a removable chiral phenyl aminal diketopiperazine substituent. The reaction sequence rapidly generates molecular complexity and is competent with both enolizable and non-enolizable aldehyde substrates. This method provides an efficient route to [2.2.2]-diazabicyclic structures, common to bioactive prenylated indole alkaloids such as the brevianamides and stephacidins.
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Paragraph 0121-0122
(2013/11/19)
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- Chemoselective formation of successive triazole linkages in one pot: "Click-click" chemistry
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A methodology for the successive regiospecific "clicking" together of three components in one pot via two triazole linkages is reported. The protocol utilizes copper(I)-mediated alkyne-azide cycloaddition reactions combined with a silver(I)-catalyzed TMS-
- Aucagne, Vincent,Leigh, David A.
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p. 4505 - 4507
(2007/10/03)
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- Pharmaceutical compositions comprising metal complexes
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A compound of the formula [Ma(XbL)cYdZe]nt±Formula I wherein: M is a metal ion or a mixture of metal ions; X is a cation or a mixture of cations; L is a ligand, or mixture of ligands each containing at least two different donor atoms selected from the elements of Group IV, Group V or Group VI of the Periodic Table; Y is a ligand or a mixture of the same or different ligands each containing at least one donor atom or more than one donor atom selected from the elements of Group IV, Group V or Group VI of the Periodic Table; and Z is a halide or pseudohalide ion or a mixture of halide ions and pseudohalide ions; and wherein: a=1-3; b=0-12; c=0-18; d=0-18; e=0-18; and n=0-10; provided that at least one of c, d and e is 1 or more; wherein c is 0: b is also 0; wherein a is 1: c, d and e are not greater than 9; and wherein a is 2: c, d and e are not greater than 12.
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- Photoinduced electron transfer (PET) promoted oxidative activation of 1- (N-benzyl-N-methylglycyl)-(S)-prolinol: Development of novel strategies towards enantioselective syntheses of α-amino acids, their N-methyl derivatives and α-hydroxy acids employing
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PET activation of 1-(N-benzyl-N-methylglycyl)-(S)-prolinol (1) in dry acetonitrile, utilizing 1,4-dicyanonaphthalene (DCN) as a light-harvesting electron-acceptor and methyl viologen (MV++) as an electron-transfer mediator, leads to the formati
- Pandey, Ganash,Das, Parthasarathi,Reddy, P. Yella
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p. 657 - 664
(2007/10/03)
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- Synthesis and Utilisation of Chiral 3-N- Benzyl-N-methylaminoperhydropyrrolo-[2,1-c][1,4]oxazin-4-one as a Novel Precursor for the Enantioselective Synthesis of α-Amino Acids and Their N-Methyl Derivatives
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α-Amino acids and their N-methyl derivatives are synthesised in good optical purity by the nucleophilic alkylation of chiral 3-N-benzyl-N-methylaminoperhydropyrrolo[2,1-c][1,4]oxazin-4-one (1). The chiral auxiliary, L-prolinol, is isolated in recyclable f
- Pandey, Ganesh,Das, Parthasarathi
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p. 634 - 639
(2007/10/03)
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- Design, synthesis, and dopamine receptor modulating activity of diketopiperazine peptidomimetics of L-prolyl-L-leucylglycinamide
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The diketopiperazine 'C5' conformational mimic has been incorporated into the L-prolyl-L-leucylglycinamide (PLG, 1) structure and into the bicyclic lactam PLG peptidomimetic structure 3 to give compounds 5 and 6, respectively. These analogues were designed to explore the idea that the N- terminal 'C5' conformation, which was found in the crystal structure of 2 and which was mimicked in 4 by the diketopiperazine function, was a factor in the high potency of these two agents. Through the use of the [3H]spiroperidol/N- propylnorapomorphine (NPA) D2 receptor competitive binding assay, both 5 and 6 were found to increase the affinity of the dopamine receptor for agonists and both were found to increase the percentage of D2 receptors which existed in the high-affinity state. These effects were observed when Gpp(NH)p was either absent or present, and they were analogous to the effects observed previously for PLG and the PLG peptidemimetics 2 and 4. However, the potency seen with 5 and 6 was less than that seen for 2 and 4, suggesting that while the N-terminal 'C5' conformation may play a role in the potency of the γ- lactam peptidomimetics of PLG, it does not appear to be the primary factor. In the 6-hydroxydopamine-lesioned animal model of Parkinson's disease, 5 altered apomorphine-induced rotational behavior in a dose-dependent manner. The maximum effect occurred at a dose of 0.01 mg/kg ip and resulted in a 52.27 ± 13.96% (p 0.001, n = 7) increase in rotations compared to apomorphine administered alone.
- Baures, Paul W.,Ojalar, William H.,Costain, Willard J.,Ott, Michael C.,Pradhan, Ashish,Gleason, William B.,Mishra, Ram K.,Johnson, Rodney L.
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p. 3594 - 3600
(2007/10/03)
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