99445-21-3

Usage

Uses

Used in Pharmaceutical Industry:
N-METHYL-3-PYRROLIDINOL is used as a solvent for the production of pharmaceuticals, facilitating the dissolution of various substances in the manufacturing process. Its ability to dissolve a wide range of compounds makes it an indispensable component in the development of new medications.
Used in Agrochemical Industry:
In the agrochemical sector, N-METHYL-3-PYRROLIDINOL is utilized as an intermediate in the synthesis of various agrochemicals. Its role in the production of these chemicals contributes to the development of effective solutions for agricultural applications.
Used in Dye and Pigment Production:
N-METHYL-3-PYRROLIDINOL is employed as a solvent in the production of dyes and pigments, enabling the creation of a diverse range of colors and shades. Its solubility properties are crucial in the formulation of these colorants for various industries.
Used in Rubber and Plastics Industry:
In the manufacturing of rubber and plastics, N-METHYL-3-PYRROLIDINOL serves as a key intermediate, contributing to the development of innovative materials with improved properties. Its role in the production process is vital for the creation of high-quality rubber and plastic products.
Overall, N-METHYL-3-PYRROLIDINOL's diverse applications across various industries highlight its importance as a chemical compound with unique properties and capabilities.

InChI:InChI=1/C5H11NO/c1-6-3-2-5(7)4-6/h5,7H,2-4H2,1H3/p+1/t5-/m0/s1

Upstream product

• 19398-47-1 1,4-dibromo-2-butanol 
• 74-89-5 methylamine 
• 554-15-4 1-methyl-2,5-dihydro-pyrrole 
• 14891-10-2 ethyl-3-oxo-1-pyrrolidinecarboxylate 
• 60-29-7 diethyl ether 
• 40499-83-0 pyrrolidin-3-ol 
• 50-00-0 formaldehyd 
• 2419-74-1 1,4-dichlorobutan-2-ol 
• 131237-81-5 3-hydroxy-N-methylsuccinimide 
• 131237-81-5 (R)-3-hydroxy-1-methyl-2,5-pyrrolidinedione 
• 40499-83-0 (3R)-pyrrolidinol 
• 104706-47-0 (R)-3-hydroxypyrrolidine hydrochloride 
• 104612-35-3 (S)-3-hydroxy-1-methyl-2,5-pyrrolidinedione 
• 122536-94-1 (S)-3-hydroxypyrrolidine hydrochloride 

Downstream Products

• 22349-82-2 C₁₂H₁₈NO⁽¹⁺⁾*Br^(1-) 
• 1404453-57-1 C₁₂H₁₈NO⁽¹⁺⁾*Cl^(1-) 
• 1404453-67-3 3-(2-cyclopentylidene-2-phenylacetoxy)-1,1-dimethylpyrrolidinium bromide 
• 1404453-52-6 1-[3-(benzylmethylamino)-2-hydroxypropyl]-3-hydroxy-1-methylpyrrolidinium bromide 
• 1001345-83-0 2-methoxy-4-(1-methylpyrrolidin-3-yl)oxy-aniline 
• 1428555-12-7 C₂₀H₂₂BrF₃N₂O₅S 
• 207856-85-7 (3S)-1-methylpyrrolidin-3-yl (2R)-2-cyclopentyl-2-hydroxy-2-phenylacetate 

Relevant academic research and scientific papers

METHOD FOR PRODUCING 1-METHYLPYRROLIDIN-3-OL

The invention relates to a method of producing compound (I) by (A) reacting compound (II) formaldehyde and hydrogen in the presence of a metal catalyst, in a solvent, wherein the amount of the formaldehyde to be used is exceeding 1 mol and not exceeding 5 mol per 1 mol of compound (II), to obtain a mixture containing the formaldehyde and compound (I), and (B) mixing the obtained mixture containing the formaldehyde and compound (I) with hydrogen and a secondary amine selected from the group consisting of diethylamine, dipropylamine, diisopropylamine, butylethylamine, pyrrolidine, piperidine and morpholine, in the presence of a metal catalyst, in a solvent, and then removing the metal catalyst, followed by obtaining the compound (I) by distillation.

Preparation method of 1-methyl-3-pyrrolidinol

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.

Widely applicable background depletion step enables transaminase evolution through solid-phase screening

Directed evolution of transaminases is a widespread technique in the development of highly sought-after biocatalysts for industrial applications. This process, however, is challenged by the limited availability of effective high-throughput protocols to evaluate mutant libraries. Here we report a rapid, reliable, and widely applicable background depletion method for solid-phase screening of transaminase variants, which was successfully applied to a transaminase from Halomonas elongata (HEWT), evolved through rounds of random mutagenesis towards a series of diverse prochiral ketones. This approach enabled the identification of transaminase variants in viable cells with significantly improved activity towards para-substituted acetophenones (up to 60-fold), as well as tetrahydrothiophen-3-one and related substrates. Rationalisation of the mutants was assisted by determination of the high-resolution wild-type HEWT crystal structure presented herein.

PROCESSES FOR MAKING, AND METHODS OF USING, GLYCOPYRRONIUM COMPOUNDS

Provided herein are processes for making and methods of using salts of glycopyrronium, including solid forms and forms suitable for use as topicals. Disclosed here are processes for making salts of glycopyrronium, also processes for making compositions comprising salts of glycopyrronium, and methods of treating hyperhidrosis with salts of glycopyrronium as well as with compositions comprising salts of glycopyrronium such as, but not limited to, topical compositions. Disclosed herein are methods of treating hyperhidrosis including administering salts of glycopyrronium to subjects in need thereof.

Preparation method of N-substituent-3-hydroxytetrahydropyrrole

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)

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.

PROCESS FOR THE EFFICIENT PREPARATION OF 3-HYDROXY PYRROLIDINE AND DERIVATIVES THEREOF

The present invention relates to an effective process for the preparation of 3-hydroxypyrrolidine or derivatives thereof. The process comprises (a) protecting a hydroxyl group of 4-halo-3-hydroxybutyric acid, (b) reducing an ester group of the compound obtained from the step (a) to obtain a corresponding alcohol compound, (c) reacting the compound obtained from the step (b) with sulfonyl halide to produce a corresponding sulfonate compound, (d) reacting the compound obtained from the step (c) with an amine to obtain 3-hydroxy-protected pyrrolidine compound, and (e) deprotecting the compound obtained from the step (d) to produce the targeted 3-hydroxypyrrolidine or derivatives thereof. The process provides 3-hydroxypyrrolidine or derivatives thereof with high optical purity, because optical purity of the starting material is substantially retained. In the process, each of the steps is carried out in a mild condition and does not require any special purification. This means that the process is useful and adequate for industrial mass production of 3-hydroxypyrrolidine and derivatives thereof having high optical purity.

Stereoisomers of N-substituted soft anticholinergics and their zwitterionic metabolite based on glycopyrrolate - Syntheses and pharmacological evaluations

Purpose. In this study, isomers of two N-substituted soft anticholinergics based on glycopyrrolate, SGM (PcPOAGP_NA.Me) and SGE (PcPOAGP_NA.Et) [3′-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1′-methyl-1′- alkoxycarbonylpyrrolidinium bromide] and their zwitterionic metabolite, SGa (PcPOAGP_NA.H) [3′-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1′- methyl-1′-carboxymethylpyrrolidinium inner salt] were synthesized and their pharmacological activities were evaluated in vitro and in vivo. Methods. The isomers of SGM and SGE were synthesized with both optically pure methyl-cyclopentylmandelate and 3-hydroxy-N-methylpyrrolidine. Trans-esterification followed by quarternization with alkyl bromoacetate gave four isomers of SGM or SGE with the nitrogen chiral center unresolved (2R3′S-SGM, 2R3′R-SGM, 2S3′S-SGM, 2S3′R-SGM or 2R3′S-SGE, 2R3′R-SGE, 2S3′S-SGE, 2S3′R-SGE). The hydrolysis of these four isomers followed by HPLC separation resulted in eight fully resolved isomers of SGa (2R3′R1′R, 2R3′S1′R, 2R3′R1′S, 2R3′S1′S, 2S3′R1′R, 2S3′S1′R, 2S3′R1′S, and 2S3′S1′S). Pharmacological activities were assessed by using in vitro receptor-binding assay and guinea pig ileum pA2-assay, and by evaluating the in vivo rabbit mydriatic effects. Results were compared to those obtained with conventional anticholinergic agents, such as glycopyrrolate, N-meythylscopolamine, and tropicamide, as well as those obtained with previously prepared racemic mixtures and 2R isomers. Results. Receptor binding pK i values at cloned human muscarinic receptors (M1-M 4 subtypes) were in the 6.0-9.5 range for the newly synthesized SGM and SGE isomers, and in the 5.0-8.6 range for the SGa isomers. In all cases, 2R isomers were significantly more active than 2S isomers (27 to 447 times for SGM isomers, and 6 to 4467 times for SGa isomers). Among the four SGM isomers with unresolved 1′ (N) chiral center, the 3′R isomers were more active than the corresponding 3′S isomers (1.5-12.9 times), whereas, among the SGa isomers, the 3′S isomers were not always more active than the corresponding 3′R isomers indicating that activity determined based on configuration at chiral center 3′ is significantly affected by the configuration of the other two chiral centers, 2 and 1′. Among the completely resolved eight SGa isomers (all three chiral centers resolved), 1′S isomers were always more active than the corresponding 1′R isomers (1.8-22.4 times). Results also indicate that some isomers showed good M3/M2 muscarinic-receptor subtype-selectivity (about 3-5 times), and 2R and 3′S were the determining configurations for this property. Guinea pig ileum assays and rabbit mydriasis tests on SGa isomers further confirmed the stereospecificity. In rabbit eyes, some 2R-SGa isomers showed mydriatic potencies similar to glycopyrrolate and exceeded tropicamide, but their mydriatic effects lasted considerably shorter, and they did not induce dilation of the pupil in the contralateral, water-treated eye. These results indicate that these compounds are locally active, but safe and have a low potential to cause systemic side effects. The pharmacological potency of the eight SGa isomers was estimated as 2R3′S1′S ≈ 2R3′R1′S ≈ 2R3′S1′R > 2R3′R1′R > 2S3′R1′S > 2S3′S1′S ≈ 2S3′R1′R > 2S3′S1′R (p 3/M2 muscarinic-receptor subtype-selectivity of soft anticholinergics, SGM, SGE, and SGa have been demonstrated. In agreement with previous results, the potential for their effective and safe use has been confirmed.

SOFT ANTICHOLINERGIC ESTERS

Soft anticholinergic esters of the formulas: wherein R1 and R2 are both phenyl or one of R1 and R2 is phenyl and the other is cyclopentyl; R is C1-C8 alkyl, straight or branched chain; and X- is an anion with a single negative charge; and wherein each asterisk marks a chiral center; said compound having the R, S or RS stereoisomeric configuration at each chiral center unless specified otherwise, or being a mixture thereof.

Identification of a novel class of succinyl-nitrile-based Cathepsin S inhibitors

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.