13220-33-2Relevant articles and documents
Preparation method of 1-methyl-3-pyrrolidinol
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Paragraph 0146-0148, (2021/09/01)
The invention relates to the technical field of synthesis of medical intermediates, and particularly discloses a preparation method of 1-methyl-3-pyrrolidinol. The preparation method comprises the following steps that S1, a compound I and a compound II are subjected to a ring closing reaction, so a compound III is obtained; and S2, the compound III obtained in the step S1 and a reducing agent IV are subjected to a reduction reaction, so 1-methyl-3-pyrrolidinol is obtained, wherein the compound I, the compound II and the compound III are as shown in the specification; and the reducing agent IV is one or more selected from a group consisting of sodium borohydride, potassium borohydride, boron trifluoride-diethyl ether and boron tribromide-diethyl ether. According to the preparation method, the compound II and the compound I are selected and subjected to the ring closing reaction to obtain the intermediate compound III, and the compound III is solid and is easy to crystallize and purify, so the purification difficulty of the intermediate is reduced, the purity of the intermediate is favorably improved, and the product quality of the 1-methyl-3-pyrrolidinol is further improved.
Preparation method of N-substituent-3-hydroxytetrahydropyrrole
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Paragraph 0022; 0023; 0024; 0025; 0026; 0027, (2017/08/29)
The invention discloses a preparation method of N-substituent-3-hydroxytetrahydropyrrole. The preparation method takes 1,2,4-butanetriol as a starting material, and comprises the following steps: performing a halogenating reaction between the starting material and hydrogen halide to prepare an intermediate 1,4-dihalogeno-2-butanol first, and then performing a condensation reaction with primary amine RNH2 to obtain a target product, wherein R represents methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tertiary butyl or benzyl; the halogenating reaction is performed in the presence of an acidic catalyst, and the acidic catalyst is formic acid or acetic acid; and hydrogen halide is hydrogen chloride or hydrogen bromide. The preparation method disclosed by the invention is relatively short in synthetic route, the starting material 1,2,4-butanetriol is low in price and easy to obtain, and other materials used in the method are relatively high in safety and also relatively low in price, so that the preparation method is suitable for industrial large-scale production. Particularly, the halogenating reaction can obtain a yield of 50% or above by selection of suitable halogenating agents and catalysts.
Carry over of impurities: A detailed exemplification for glycopyrrolate (NVA237)
Allmendinger, Thomas,Bixel, Dominique,Clarke, Adrian,Di Geronimo, Laura,Fredy, Jean-Wilfried,Manz, Marco,Gavioli, Elena,Wicky, Regine,Schneider, Martin,Stauffert, Fabien J.,Tibi, Markus,Valentekovic, Darko
supporting information, p. 1754 - 1769 (2013/01/15)
The original synthesis of glycopyrrolate (NVA237) was revised and shortened into an essentially one-pot process. Without isolating the intermediates, their purification became obsolete, thereby increasing the possibility of the carry over of impurities. For that reason, the actual, potential, and theoretical impurities of the starting materials cyclopentyl mandelic acid and 1-methyl-pyrrolidin-3-ol as well as byproducts which may occur during the synthesis were thoroughly investigated; furthermore, their transformation to possible impurities in the drug substance along the new synthetic route was performed to exclude them as actual impurities in the drug substance with certainty. The question is raised how detailed such investigation-which are fairly manageable for a simple product like glycopyrrolate-need to be.
Identification of a novel class of succinyl-nitrile-based Cathepsin S inhibitors
Bekkali, Younes,Thomson, David S.,Betageri, Raj,Emmanuel, Michel J.,Hao, Ming-Hong,Hickey, Eugene,Liu, Weimin,Patel, Usha,Ward, Yancey D.,Young, Erick R.R.,Nelson, Richard,Kukulka, Alison,Brown, Maryanne L.,Crane, Kathy,White, Della,Freeman, Dorothy M.,Labadia, Mark E.,Wildeson, Jessi,Spero, Denice M.
, p. 2465 - 2469 (2008/03/11)
The synthesis and in vitro activities of a series of succinyl-nitrile-based inhibitors of Cathepsin S are described. Several members of this class show nanomolar inhibition of the target enzyme as well as cellular potency. The inhibitors displaying the greatest potency contain N-alkyl substituted piperidine and pyrrolidine rings spiro-fused to the α-carbon of the P1 residue.
Process for preparing 3-pyrrolidinols
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, (2008/06/13)
A novel process is disclosed for the preparation of 3-pyrrolidinol compounds selected from the group having the formula: STR1 wherein: R is selected from hydrogen, loweralkyl, loweralkenyl, cycloalkyl, cycloalkyl-loweralkyl, phenyl-loweralkyl and substituted phenyl-loweralkyl; R1, R2, and R3 are selected from hydrogen, loweralkyl, and loweralkenyl; and the optical isomers thereof. In the process, 4-amino-3-hydroxybutyronitriles are reductively cyclized with Raney nickel to produce the 3-pyrrolidinol compound.
N-substituted 3-aminopyrrolidines
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, (2008/06/13)
The compounds 3-(N-diethylcarbamyl)amino-1-methyl pyrrolidine, 3-(N-carbethoxy-N-methyl)amino-1-methyl pyrrolidine, 1-diethylcarbamyl-3-(N-methyl)amino pyrrolidine and 1-diethylcarbamyl-3-dimethylamino pyrrolidine, said compounds having utility as antifilarial agents.
