41720-98-3

Usage

Uses

Used in Pharmaceutical Industry:
(R)-2-Methyl-pyrrolidine is used as a building block for the synthesis of chiral naphthalenoid histamine receptor antagonists. It plays a crucial role in the development of multikilogram quantities of these compounds, which are essential for the treatment of various medical conditions related to histamine receptor activity.
Used in Organic Synthesis:
(R)-2-Methyl-pyrrolidine is used as a versatile building block in organic synthesis for the creation of various chiral compounds with potential applications in different industries, such as pharmaceuticals, agrochemicals, and materials science. Its unique structure and stereochemistry make it a valuable component in the synthesis of enantiomerically pure compounds.

InChI:InChI=1/C5H11N/c1-5-3-2-4-6-5/h5-6H,2-4H2,1H3/t5-/m1/s1

Upstream product

• 765-38-8 2-methyl-1-pyrrolidine 
• 122970-63-2 2-Methylpyrroline 
• 108-27-0 5-methylpyrrolidin-2-one 
• 22537-07-1 4-pentenyl-1-amine 
• 592-51-8 4-Pentenenitrile 
• 117607-13-3 (R)-2-methylpyrrolidine hydrobromide 
• 1009105-76-3 1-(4-chlorobenzyl)-2-methylpyrrolidine 
• 1218989-50-4 (R)-1-((S)-2-methyl-propane-2-sulfinyl)-2-methyl-pyrrolidine 
• 51547-88-7 (2R)-1-tosyl-2-methylpyrrolidine 
• 872-32-2 2-methyl-1H-pyrroline 
• 69610-40-8 N-(tert-butoxycarbonyl)-L-prolinol 
• 774-91-4 (S)-1-benzyl-2-methylpyrrolidine 
• 626-95-9 1,4-Pentanediol 
• 1218989-56-0 (S)-1-((S)-2-methyl-propane-2-sulfinyl)-2-methyl-pyrrolidine 

Downstream Products

• 102536-11-8 ((R)-2-Methyl-pyrrolidin-1-yl)-phenyl-amine 
• 124096-31-7 (R)-2,2,2-trifluoro-1-<2-(2-methyl-1-pyrrolidinyl)phenyl>ethanone 
• 460747-73-3 (R)-1-(but-3-yn-1-yl)-2-methylpyrrolidine 
• 689290-83-3 4-(6-{2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl}-2-naphthyl)benzonitrile 
• 921616-75-3 1,1-dimethylethyl 4-[4-({3-[(R)-2-methyl-1-pyrrolidinyl]propyl}oxy)phenyl]-3-oxo-1-piperazinecarboxylate 
• 1146415-33-9 2-(2R)-methyl-[1,3']bipyrrolidinyl dihydrochloride 
• 1202647-41-3 (R)-1-(2-bromo-benzenesulfonyl)-2-methyl-pyrrolidine 
• 1152749-34-2 (2R)-1-[2-(4-iodophenoxy)ethyl]-2-methylpyrrolidine 
• 1152749-37-5 (2R)-1-[4-(4-iodophenoxy)butyl]-2-methylpyrrolidine 
• 157007-54-0 2-(R)-methylpyrrolidine-1-carboxylic acid tert-butyl ester 

Relevant academic research and scientific papers

A method for the racemization of 2-methylpyrrolidine: A histamine H 3 receptor pharmacophore

This paper describes a method for the racemization of unwanted (S)-1 isomer arising from the resolution of (±)-1. The process of racemization involves thiyl radical-mediated reversible hydrogen abstraction at the chiral center, in the presence of AIBN in water. The racemized isomer was subsequently resolved by l-(+)-tartaric acid to get (R)-1, a histamine H3 receptor pharmacophore. We foresee that such an approach of racemization will be industrially useful for recycling waste (S)-1 enantiomer.

Switching the Cofactor Specificity of an Imine Reductase

In the last years, imine reductases (IREDs) have gained importance for the formation of chiral amines by catalyzing asymmetric reductions of imines and chemo- and stereoselective reductive aminations. However, all characterized members of this steadily gr

Enzyme Toolbox: Novel Enantiocomplementary Imine Reductases

Reducing reactions are among the most useful transformations for the generation of chiral compounds in the fine-chemical industry. Because of their exquisite selectivities, enzymatic approaches have emerged as the method of choice for the reduction of C=O

Purification and characterization of a novel (R)-imine reductase from Streptomyces sp. GF3587

The (R)-imine reductase (RIR) of Streptomyces sp. GF3587 was purified and characterized. It was found to be a NADPH-dependent enzyme, and was found to be a homodimer consisting of 32 kDa subunits. Enzymatic reduction of 10mM 2-methyl-1-pyrroline (2-MPN) resulted in the formation of 9.8mM (R)-2-methylpyrrolidine ((R)-2-MP) with 99% e.e. The enzyme showed not only reduction activity for 2-MPN at neutral pH (6.5- 8.0), but also oxidation activity for (R)-2-MP under alkaline pH (10-11.5) conditions. It appeared to be a sulfhydryl enzyme based on the sensitivity to sulfhydryl specific inhibitors. It was very specific to 2-MPN as substrate.

Acylative kinetic resolution of racemic methyl-substituted cyclic alkylamines with 2,5-dioxopyrrolidin-1-yl (: R)-2-phenoxypropanoate

The diastereoselective acylation of a number of racemic methyl-substituted cyclic alkylamines with active esters of 2-phenoxypropanoic acid was studied in detail. The ester of (R)-2-phenoxypropanoic acid and N-hydroxysuccinimide was found to be the most selective agent. The highest stereoselectivity was observed in the kinetic resolution of racemic 2-methylpiperidine in toluene at -40 °C (selectivity factor s = 73) with the predominant formation of (R,R)-amide (93.7% de). To explain the observed stereoselectivity, DFT modelling of the transition states in the reactions of the title acylating agent with 2-methylpiperidine and 2-methylpyrrolidine was performed. The calculated values were in good agreement with experimental data. It has been demonstrated that the acylation proceeds via a concerted mechanism, in which the addition of an amine occurs simultaneously with the elimination of the hydroxysuccinimide fragment. The high stereoselectivity of the (R,R)-amide formation is largely ensured by the lower steric hindrances in the transition states as compared to the formation of (R,S)-amide.

Production method of (R)-2-methylpyrrolidine hydrochloride

The invention provides a production method of (R)-2-methylpyrrolidine hydrochloride. The method is an industrial production method and adopts a reduction method of sodium borohydride and different solvents to obtain the (R)-2-methylpyrrolidine hydrochloride with the product purity of 98% or above and the product total yield of 70% or above. Also provided is a process for the synthesis of chiral (R)-2-methylpyrrolidine hydrochloride. Meanwhile, raw materials adopted in the method are easy to obtain, synthesis conditions are simple, the product yield is high, and the method is suitable for industrial production.

One-Pot Synthesis of Chiral N-Arylamines by Combining Biocatalytic Aminations with Buchwald–Hartwig N-Arylation

The combination of biocatalysis and chemo-catalysis increasingly offers chemists access to more diverse chemical architectures. Here, we describe the combination of a toolbox of chiral-amine-producing biocatalysts with a Buchwald–Hartwig cross-coupling reaction, affording a variety of α-chiral aniline derivatives. The use of a surfactant allowed reactions to be performed sequentially in the same flask, preventing the palladium catalyst from being inhibited by the high concentrations of ammonia, salts, or buffers present in the aqueous media in most cases. The methodology was further extended by combining with a dual-enzyme biocatalytic hydrogen-borrowing cascade in one pot to allow for the conversion of a racemic alcohol to a chiral aniline.

Stereoselective Biotransformations of Cyclic Imines in Recombinant Cells of Synechocystis sp. PCC 6803

Light-driven biotransformations in recombinant cyanobacteria allow to employ photosynthetic water-splitting for cofactor-regeneration and thus, to save the use of organic electron donors. The genes of three recombinant imine reductases (IREDs) were expressed in the cyanobacterium Synechocystis sp. PCC 6803 and eight cyclic imine substrates were screened in whole-cell biotransformations. While initial reactions showed low to moderate rates, optimization of the reaction conditions in combination with promoter engineering allowed to alleviate toxicity effects and achieve full conversion of prochiral imines with initial rates of up to 6.3 mM h?1. The high specific activity of up to 22 U gCDW ?1 demonstrates that recombinant cyanobacteria can provide large amounts of NADPH during whole cell reactions. The excellent optical purity of the products with up to >99 %ee underlines the usefulness of cyanobacteria for the stereoselective synthesis of amines.

Dihydrogen-Driven NADPH Recycling in Imine Reduction and P450-Catalyzed Oxidations Mediated by an Engineered O2-Tolerant Hydrogenase

The O2-tolerant NAD+-reducing hydrogenase (SH) from Ralstonia eutropha (Cupriavidus necator) has already been applied in vitro and in vivo for H2-driven NADH recycling in coupled enzymatic reactions with various NADH-dependent oxidoreductases. To expand the scope for application in NADPH-dependent biocatalysis, we introduced changes in the NAD+-binding pocket of the enzyme by rational mutagenesis, and generated a variant with significantly higher affinity for NADP+ than for the natural substrate NAD+, while retaining native O2-tolerance. The applicability of the SH variant in H2-driven NADPH supply was demonstrated by the full conversion of 2-methyl-1-pyrroline into a single enantiomer of 2-methylpyrrolidine catalysed by a stereoselective imine reductase. In an even more challenging reaction, the SH supported a cytochrome P450 monooxygenase for the oxidation of octane under safe H2/O2 mixtures. Thus, the re-designed SH represents a versatile platform for atom-efficient, H2-driven cofactor recycling in biotransformations involving NADPH-dependent oxidoreductases.

Synthesis and evaluation of in vivo anti-hypothermic effect of all stereoisomers of the thyrotropin-releasing hormone mimetic: Rovatirelin Hydrate

We discovered the orally active thyrotropin-releasing hormone (TRH) mimetic: (4S,5S)-5-methyl-N-{(2S)-1-[(2R)-2-methylpyrrolidin-1-yl]-1-oxo-3-(1,3-thiazol-4-yl)propan-2-yl}-2-oxo-1,3-oxazolidine-4-carboxamide 1 (rovatirelin). The central nervous system (CNS) effect of rovatirelin after intravenous (iv) administration is 100-fold higher than that of TRH. As 1 has four asymmetric carbons in its molecule, there are 16 stereoisomers. We synthesized and evaluated the anti-hypothermic effect of all stereoisomers of 1, which has the (4S),(5S),(2S),(2R) configuration from the N-terminus to the C-terminus, in order to clarify the structure?activity relationship (SAR) of stereoisomers. The (4R),(5R),(2R),(2S)-isomer 16 did not show any anti-hypothermic effect. Only the (4S),(5S),(2S),(2S)-isomer 10, which has the (2S)-2-methylpyrrolidine moiety at the C-terminus showed the anti-hypothermic effect similar to 1. Stereoisomers, which have the (5R) configuration of the oxazolidinone at the N-terminus and the (2R) configuration at the middle-part, showed a much lower anti-hypothermic effect than that of 1. On the other hand, stereoisomers, which have the (4R) configuration of the oxazolidinone at the N-terminus or the (2S) configuration of the C-terminus, have little influence on the anti-hypothermic effect.