69676-65-9Relevant academic research and scientific papers
Preparation method of amlodipine intermediate
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Paragraph 0066-0080, (2020/09/16)
The invention provides a preparation method of an amlodipine intermediate, belonging to the technical field of bulk drug synthesis. The preparation method comprises the following steps: mixing a compound 1 (2-(2-(2-hydroxyethoxy)ethyl)isoindoline-1,3-dione), an N-O free radical catalyst, a metal salt catalyst and a first organic solvent, and carrying out an oxidation reaction under the action of an oxidizing agent to obtain a compound 2, wherein the oxidizing agent is air or oxygen; mixing the compound 2, an acylating chlorination reagent and a second organic solvent, and carrying out an acylating chlorination reaction to obtain a compound 3; and mixing the compound 3, monopotassium malonate, tertiary amine and a third organic solvent, and carrying out a C-acylation reaction to obtain theamlodipine intermediate. The method provided by the invention has the advantages of usage of cheap and easily available raw materials, less three-waste pollution, high process safety, simplicity and convenience in operation and easiness in industrial production.
PREPARATION METHOD OF 2-(2-PHTHLIMIDOETHOXY) ACETIC ACID
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Paragraph 0445 - 0048, (2016/10/07)
PURPOSE: A method for preparing 2-(2-phthalimidoethoxy)acetic acid is provided to cheaply obtain 2-(2-phthalimidoethoxy)acetic acid of high purity. CONSTITUTION: A 2-(2-phthalimidoethoxy)acetic acid is prepared by dropping sodium chloride(NaClO_2) solution and sodium hyperchloride(NaOCl) solution to 2-(2-phthalimidoethoxy)ethanol of chemical formula 3 under the presence of 2,2,6,6-tetramethylpiperidine 1-oxyl(TEMPO) catalyst and oxidizing 2-(2-phthalimidoethoxy)ethanol. The 2-(2-phthalimidoethoxy)ethanol is used in an organic solvent of nitrile, ketone, haloalkan, or ester or water and buffer solution. The organic solvent is aceto nitrile, acetone, methyl ethyl ketone, dichlomethane, dichloroethan, or ethyl acetate.
Synthesis of Medium- and Large-Ring Compounds Initiated by Photochemical Decarboxylation of ω-Phthalimidoalkanoates
Griesbeck, Axel G.,Henz, Andreas,Kramer, Wolfgang,Lex, Johann,Nerowski, Frank,Oelgemoeller, Michael,Peters, Karl,Peters, Eva-Maria
, p. 912 - 933 (2007/10/03)
The synthesis of a variety of hydroxylactams from ω-phthalimidoalkanoates using a triplet-sensitized photodecarboxylation reaction initiated by intramolecular photo electron transfer is described. Ring sizes available by this method span from 4 (benzazepine-1,5-dione 7) to 26 (cyclodipeptide 26e). Ground-state template formation is proposed as the explanation for the high efficiency of this reaction and for the decrease in reactivity in the presence of organic bases instead of metal carbonates. The crucial step in this macrocyclization reaction seems to be the protonation of the intermediary ketyl radiais (Scheme 4). Spacer groups investigated were alkyl chains (C3-C11: 5c-h, 11a, 12), ether (16, 18), ester (20, 22), and amide (26a-f) linkages. Within the detection limits, no dimeric (= decarboxylative coupling) products were observed, indicating the high preference for intra-vs. intermolecular photoelectron transfer. The C,C radical combination step proceeds with low stereoselectivity (cf. products 11 and 12) in contrast to comparable singlet reactions. Except for the lactones 22, all products were stable under the photolysis conditions. Prolonged irradiation of 22 led to the formation of the spiro compounds 23, probably via an intermediary acyliminium betaine (Scheme 8). One serious limitation of the decarboxylative macrocyclization is its incompatibility with the glycine spacer (as in 27a and 27b), probably the consequence of a strong intramolecular H-bond (Scheme 10).
N-acyldipeptides, processes for the preparation thereof and pharmaceutical compositions containing the same
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, (2008/06/13)
N-acyldipeptides of formula I STR1 wherein R represents a rest of formula STR2 and R4, Y, m, n and Z have the meaning as defined in the description, R1 represents hydrogen, a 1-10 C. alkyl, an optionally substituted methyl or benzyl,
Pseudopeptide analogues of substance P and leucine enkephalinamide containing the Ψ(CH2O) modification: Synthesis and biological activity
Roubini,Laufer,Gilon,Selinger,Roques,Chorev
, p. 2430 - 2438 (2007/10/02)
The isosteric methyleneoxy Ψ(CH2O) function was employed as a novel peptide-bond surrogate and incorporated into sequences of two neuropeptides, substance P (SP) and enkephalin. A pseudopeptide analogue [pGlu6,Phe8Ψ(CHsub
Synthesis of Specifically Deuterium Labeled Sulfur and Oxygen Ether Side-Chain-Extended Antileukemic (2-Chloroethyl)nitrosoureas and Study of Their Products and Pathways of Decomposition under Physiological Conditions
Lown, J. William,Koganty, R. Rao,Joshua, Alummoottil V.
, p. 2027 - 2033 (2007/10/02)
The synthesis of certain specifically deuterium labeled ether and thioether side-chain-extended (2-chloroethyl)nitrosoureas is described.Controlled aqueous decomposition of α-d2-S-CENU and β-d2-S-CENU under physiological conditions affords six products including 2-chloroethyl vinyl ether, bis(2-chloroethyl)thioether, and 1,2-dihydrothiophenes.The reactions, which are dominated by elimination under these conditions, the products, and the distribution of isotopic labels are consistent with the formation of thiiranium intermediates which are then subject to ring opening and ring expansion.Similar decomposition of α-d2-O-CENU and β-d2-O-CENU affords seven products including the 2-chloroethyl vinyl ether, acetalaldehyde, vinyl chloride, and bis(2-chloroethyl) ether but no dihydrofuran.The products and isotope distributions in these cases are consistent with an oxiranium species formed at the demand of the incipient cationic center but not formed at the ω-position.The rates of aqueous decomposition of α-d2-S-CENU, and α-d2-O-CENU show no isotope effects in accord with the suggested rate-determining step.In contrast, the 2-chloroethyl vinyl ether (or thioether) product distributions, corresponding to elimination of a proton or deuteron, of 4:1 for α-d2-S-CENU and 15:1 for α-d2-O-CENU are in accord with large primary isotope effects at the stage of the intermediate thiiranium or oxiranium ions.The overall results are in accord with the observed property of S-CENU to cross-link DNA readily due to sulfur participation at two sites unlike O-CENU which only alkylates and does not cross-link DNA.These results may relate to the superior antileukemic activity of S-CENU.
