104641-60-3

Basic information

• Product Name: (R)-(-)-1-Methyl-3-pyrrolidinol
• Synonyms: (R)-N-Methyl-3-pyrrolidinol;(3R)-1-Methylpyrrolidin-3-ol;3-Pyrrolidinol,1-methyl-, (3R)-;(R)-N-Methyl-3-pyrrolidinol,99%e.e.;(R)-(-)-1-METHYL-3-PYRROLIDINOL;(R)-1-METHYL-3-PYRROLIDINOL;(R)-(-)-1-METHYL-3-HYDROXYPYRROLIDINE;(R)-1-METHYLPYRROLIDIN-3-OL
• CAS NO: 104641-60-3
• Molecular Formula: C₅H₁₁NO
• Molecular Weight: 101.15
• EINECS: -0
• Product Categories: Pyrrole&Pyrrolidine&Pyrroline;Chiral Building Blocks;Simple Alcohols (Chiral);Synthetic Organic Chemistry
• Mol File: 104641-60-3.mol

Chemical Properties

• Boiling Point: 50-52 °C1 mm Hg(lit.)
• Flash Point: 159 °F
• Appearance: Colorless to yellow to brown/Liquid
• Density: 0.921 g/mL at 25 °C(lit.)
• Refractive Index: n20/D 1.4640(lit.)
• Storage Temp.: Inert atmosphere,Room Temperature
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 14.95±0.20(Predicted)
• Sensitive: Air Sensitive & Hygroscopic
• BRN: 4349393
• CAS DataBase Reference: (R)-(-)-1-Methyl-3-pyrrolidinol(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-(-)-1-Methyl-3-pyrrolidinol(104641-60-3)
• EPA Substance Registry System: (R)-(-)-1-Methyl-3-pyrrolidinol(104641-60-3)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• RIDADR: NA 1993 / PGIII
• WGK Germany: 3
• Hazardous Substances Data: 104641-60-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(R)-(-)-1-Methyl-3-pyrrolidinol is used as a synthetic intermediate for the asymmetric synthesis of constrained (-)-S-adenosyl-L-homocysteine (SAH) analogs. These analogs serve as DNA methyltransferase inhibitors, playing a crucial role in the development of potential therapeutic agents for various diseases, including cancer and other genetic disorders.
Used in Chemical Synthesis:
(R)-(-)-1-Methyl-3-pyrrolidinol is also utilized in the synthesis of other complex organic molecules and compounds. Its unique structure and properties make it a valuable building block for the creation of new chemical entities with potential applications in various industries, such as pharmaceuticals, agrochemicals, and materials science.

Upstream product

• 131237-81-5 (R)-3-hydroxy-1-methyl-2,5-pyrrolidinedione 
• 50-00-0 formaldehyd 
• 104706-47-0 (R)-3-hydroxypyrrolidine hydrochloride 
• 40499-83-0 (3R)-pyrrolidinol 

Downstream Products

• 895149-14-1 1-((S)-1-methyl-pyrrolidin-3-yl)-4,4-diphenyl-imidazolidin-2-one 
• 895148-84-2 3-((S)-1-methyl-pyrrolidin-3-yl)-5,5-diphenyl-imidazolidine-2,4-dione 
• 1430472-56-2 (R)-1-methyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)pyrrolidine 
• 1355683-07-6 C₂₇H₂₈F₃N₃O₅S 
• 1379513-77-5 (R)-1-methylpyrrolidin-3-yl 2-(tert-butoxycarbonylamino)-2-phenylacetate 
• 1233326-74-3 (R)-1-methylpyrrolidin-4-yl-2-phenyl-2-(phenylamino)acetate 
• 616866-21-8 (2R,3'R)-3'-(2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1'-methylpyrrolidine 
• 1197848-64-8 (R)-N-((6-chloro-2-(4-fluorophenyl)imidazo[1,2-a]pyridin-3-yl)methyl)-4-(1-methylpyrrolidin-3-yloxy)pyrimidin-2-amine 
• 1061749-60-7 N-{2-(3,5-dimethyl-pyrazol-1-yl)-6-[3-((R)-1-methyl-pyrrolidin-3-yloxymethyl)phenyl]-pyrimidin-4-yl}-acetamide 

Relevant articles and documents

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.

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.

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.

NEW PYRROLIDINIUM DERIVATIVES

New pyrrolidinium derivatives having the chemical structure of general formula (I) are disclosed; as well as processes for their preparation, pharmaceutical compositions comprising them and their use in therapy as antagonists of M3 muscarinic receptors.

Optical Isomers of Rocastine and Close Analogues: Synthesis and H1 Antihistaminic Activity of Its Enantiomers and Their Structural Relationship to the Classical Antihistamines

The enantiomers of 2--3,4-dihydro-4-methylpyrido-1,4-oxazepine-5(2H)-thione (rocastine) and two of its more potent analogues were prepared with an enantiomeric purity of > 99.9percent.The antihistaminic activity of these compounds was assessed by their ability to block histamine-induced lethality in guinea pigs and to inhibit mepyramine binding to guinea pig cortex.In this series, compounds having the R configuration at the 2-position are at least 300 times more potent than the S isomers.Conformational analysis and molecular modeling suggest that rocastine can adopt a conformation in which the pyridine ring, ether oxygen, and protonated amine functions are positioned similarly to the corresponding elements of the probable binding conformers of some of the more classical antihistamines.This conformation, boatlike in the oxazepine ring with the side chain quasi-equatorial and folded back toward the ring, is the likely binding conformer at the histamine H1 receptor, and the available structure-activity relationship data is consistent with this interpretation.

Fused aromatic oxazepinones, thiazepinones, diazepinones and sulfur analogs thereof

Aromatic azepinones and thiones having the formula STR1 wherein; A is benzene, naphthalene, quinoline or pyridine; B is oxygen or sulfur; E is oxygen, sulfur or STR2 n is 1, 2 or 3; Z is an amino or a heterocyclic nitrogen-containing radical; R is hydrogen, loweralkyl, cycloalkyl or phenylloweralkyl; Y is halo, loweralkyl, loweralkoxy, diloweralkylamino, nitro, amino, loweracetylamino, trifluoromethyl, phenyl or phenyl substituted by one to three Y' radicals selected from halo, loweralkyl, loweralkoxy, diloweralkylamino, nitro, amino, loweracylamino or trifluoromethyl; and having antihistaminic utility, a process for the preparation thereof and chemical intermediates therefor are disclosed.

Fused aromatic oxazepinones, thiazepinones, diazepinones and sulfur analogs thereof

Aromatic azepinones and thiones having the formula STR1 wherein; A is benzene, naphthalene, quinoline or pyridine; B is oxygen or sulfur; E is oxygen, sulfur or STR2 n is 1, 2 or 3; Z is an amino or a heterocyclic nitrogen containing radical; R is hydrogen, loweralkyl, cycloalkyl or phenylloweralkyl; and having antihistaminic utility, a process for the preparation thereof and chemical intermediates therefor are disclosed.