3197-42-0

Usage

Uses

Used in Pharmaceutical Industry:
(S)-(+)-2-Methylpiperidine is used as a key intermediate in the synthesis of (S)-N-(3-(2-pipecolin-1-yl)propyl)phthalimide, a compound with potential pharmaceutical applications. It serves as a crucial component in the development of new drugs, contributing to the advancement of medical treatments.
Used in Organic Synthesis:
(S)-(+)-2-Methylpiperidine is used as a starting material in the multi-step synthesis of (2S,6S)-(+)-solenopsin A, a complex organic molecule with potential applications in various fields. Its unique structure and stereochemistry make it an essential component in the creation of complex organic compounds, driving innovation in organic chemistry.

InChI:InChI=1/C6H13N/c1-6-4-2-3-5-7-6/h6-7H,2-5H2,1H3/t6-/m0/s1

Upstream product

• 109-05-7 2-Methylpiperidin 
• 153681-99-3 (S)-N-benzyl-N-(Z)-(1-methyl-4-trimethylsilylbut-3-enyl)amine 
• 119461-42-6 (S)-N-(p-toluenesulfonyl)-4-amino-1-Z-(trimethylsilyl)-1-pentene 
• 5261-58-5 methylpentamethylenediamine 
• 155322-82-0 (3R,5S,8aS)-1-Benzyl-5-methyl-3-phenyl-octahydro-imidazo[1,2-a]pyridine 
• 170710-79-9 (3S,8aR)-8a-Methyl-3-phenyl-hexahydro-oxazolo[3,2-a]pyridin-5-one 
• 153681-98-2 N-Benzyl-4-methyl-N-((Z)-(S)-1-methyl-4-trimethylsilanyl-but-3-enyl)-benzenesulfonamide 
• 153682-00-9 Benzyl-((Z)-(S)-1-methyl-4-trimethylsilanyl-but-3-enyl)-trimethylsilanylmethyl-amine 
• 321885-26-1 (S)-6-Methyl-1-((R)-1-phenyl-ethyl)-piperidin-2-one 
• 321885-24-9 N-isopropenyl-N-(1-phenyl-ethyl)-acrylamide 
• 321885-28-3 (S)-2-Methyl-1-[(R)-1-phenylethyl]piperidine 
• 709669-82-9 (2E,5S,αS)-ethyl 5-(N-benzyl-N-α-methylbenzylamino)hex-2-enoate 
• 737760-86-0 (S)-4-isopropyl-3-(6-methylpyridin-2-yl)oxazolidin-2-one 
• 183903-99-3 (+)-(S)-N-tert-butoxycarbonyl-2-methylpiperidine 

Downstream Products

• 3197-43-1 (S)-(+)-2-methyl-1-(4-toluenesulfonyl)piperidine 
• 406694-46-0 (S)-2-(2-methylpiperidin-1-yl)ethan-1-ol 
• 183903-99-3 (+)-(S)-N-tert-butoxycarbonyl-2-methylpiperidine 
• 109-05-7 2-Methylpiperidin 
• 1396753-93-7 (S)-2-(2,4-difluorophenyl)-3-(2-methylpiperidin-1-yl)quinoxaline-6-carboxylic acid 
• 1396753-94-8 (S)-methyl 2-(2,4-difluorophenyl)-3-(2-methylpiperidin-1-yl)quinoxaline-6-carboxylate 
• 1430810-30-2 (S)-1-(4-(2-methylpiperidin-1-ylsulfonyl)phenyl)pyrrolidin-2-one 
• 1430810-46-0 (S)-1-(4-iodophenylsulfonyl)-2-methylpiperidine 

Relevant academic research and scientific papers

A Novel (R)-Imine Reductase from Paenibacillus lactis for Asymmetric Reduction of 3 H-Indoles

A novel (R)-imine reductase (PlRIR) from Paenibacillus lactis was heterologously overexpressed in Escherichia coli, purified and characterized. The purified PlRIR exhibited relatively high catalytic efficiency (kcat/Km=1.58 s-1 mm-1) towards 2,3,3-trimethylindolenine. A panel of 3H-indoles and 3H-indole iodides were reduced by PlRIR to yield the corresponding products with good-to-excellent enantioselectivity (66-98 % ee). In addition, PlRIR also possesses good activities toward other types of imines such as pyrroline, tetrahydropyridine, and dihydroisoquinoline, indicating a reasonably broad substrate acceptance. In a 100 mg scale preparative reaction, 100 mm 2,3,3-trimethylindolenine was converted efficiently to afford (R)-2,3,3-trimethylindoline with 96 % ee and 81 % yield.

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.

Synthesis of: N -heterocycles from diamines via H2-driven NADPH recycling in the presence of O2

Herein, we report an enzymatic cascade involving an oxidase, an imine reductase and a hydrogenase for the H2-driven synthesis of N-heterocycles. Variants of putrescine oxidase from Rhodococcus erythropolis with improved activity were identified. Substituted pyrrolidines and piperidines were obtained with up to 97% product formation in a one-pot reaction directly from the corresponding diamine substrates. The formation of up to 93% ee gave insights into the specificity and selectivity of the putrescine oxidase.

Sequence-Based In-silico Discovery, Characterisation, and Biocatalytic Application of a Set of Imine Reductases

Imine reductases (IREDs) have recently become a primary focus of research in biocatalysis, complementing other classes of amine-forming enzymes such as transaminases and amine dehydrogenases. Following in the footsteps of other research groups, we have established a set of IRED biocatalysts by sequence-based in silico enzyme discovery. In this study, we present basic characterisation data for these novel IREDs and explore their activity and stereoselectivity using a panel of structurally diverse cyclic imines as substrates. Specific activities of >1 U/mg and excellent stereoselectivities (ee>99 %) were observed in many cases, and the enzymes proved surprisingly tolerant towards elevated substrate loadings. Co-expression of the IREDs with an alcohol dehydrogenase for cofactor regeneration led to whole-cell biocatalysts capable of efficiently reducing imines at 100 mM initial concentration with no need for the addition of extracellular nicotinamide cofactor. Preparative biotransformations on gram scale using these ‘designer cells’ afforded chiral amines in good yield and excellent optical purity.

Identification of an Imine Reductase for Asymmetric Reduction of Bulky Dihydroisoquinolines

A new imine reductase from Stackebrandtia nassauensis (SnIR) was identified, which displayed over 25- to 1400-fold greater catalytic efficiency for 1-methyl-3,4-dihydroisoquinoline (1-Me DHIQ) compared to other imine reductases reported. Subsequently, an efficient SnIR-catalyzed process was developed by simply optimizing the amount of cosolvent, and up to 15 g L-1 1-Me DHIQ was converted completely without a feeding strategy. Furthermore, the reaction proceeded well for a panel of dihydroisoquinolines, affording the corresponding tetrahydroisoquinolines (mostly in S-configuration) in good yields (up to 81%) and with moderate to excellent enantioselectivities (up to 99% ee).

Asymmetric Reductive Amination of Ketones Catalyzed by Imine Reductases

Biocatalysis employing imine reductases is a promising approach for the one-step generation of chiral amines from ketones. The enzymes reported for this process suffer from low activity and moderate stereoselectivity. We identified a set of enzymes that facilitate this reaction with high to quantitative conversions from a library of 28 imine reductases. This enabled the conversion of ketones with ammonia, methylamine, or butylamine into the corresponding amines. Most importantly, we performed preparative (>100 mg) scale syntheses of amines such as (1S,3R)-N,3-dimethylcyclohexylamine and (R)-N-methyl-2-aminohexane with excellent stereochemical purities (98 % de, 96 % ee) in good yields.

Stereoselectivity and Structural Characterization of an Imine Reductase (IRED) from Amycolatopsis orientalis

The imine reductase AoIRED from Amycolatopsis orientalis (Uniprot R4SNK4) catalyzes the NADPH-dependent reduction of a wide range of prochiral imines and iminium ions, predominantly with (S)-selectivity and with ee's of up to >99%. AoIRED displays up to 100-fold greater catalytic efficiency for 2-methyl-1-pyrroline (2MPN) compared to other IREDs, such as the enzyme from Streptomyces sp. GF3546, which also exhibits (S)-selectivity, and thus, AoIRED is an interesting candidate for preparative synthesis. AoIRED exhibits unusual catalytic properties, with inversion of stereoselectivity observed between structurally similar substrates, and also, in the case of 1-methyl-3,4-dihydroisoquinoline, for the same substrate, dependent on the age of the enzyme after purification. The structure of AoIRED has been determined in an "open" apo-form, revealing a canonical dimeric IRED fold in which the active site is formed between the N- and C-terminal domains of participating monomers. Co-crystallization with NADPH gave a "closed" form in complex with the cofactor, in which a relative closure of domains, and associated loop movements, has resulted in a much smaller active site. A ternary complex was also obtained by cocrystallization with NADPH and 1-methyl-1,2,3,4-tetrahydroisoquinoline [(MTQ], and it reveals a binding site for the (R)-amine product, which places the chiral carbon within 4 ? of the putative location of the C4 atom of NADPH that delivers hydride to the C? -N bond of the substrate. The ternary complex has permitted structure-informed mutation of the active site, resulting in mutants including Y179A, Y179F, and N241A, of altered activity and stereoselectivity.

Structure, activity and stereoselectivity of NADPH-dependent oxidoreductases catalysing the S-selective reduction of the imine substrate 2-methylpyrroline

Oxidoreductases from Streptomyces sp. GF3546 [3546-IRED], Bacillus cereus BAG3X2 (BcIRED) and Nocardiopsis halophila (NhIRED) each reduce prochiral 2-methylpyrroline (2MPN) to (S)-2-methylpyrrolidine with >95 % ee and also a number of other imine substrates with good selectivity. Structures of BcIRED and NhIRED have helped to identify conserved active site residues within this subgroup of imine reductases that have S selectivity towards 2MPN, including a tyrosine residue that has a possible role in catalysis and superimposes with an aspartate in related enzymes that display R selectivity towards the same substrate. Mutation of this tyrosine residue - Tyr169 - in 3546-IRED to Phe resulted in a mutant of negligible activity. The data together provide structural evidence for the location and significance of the Tyr residue in this group of imine reductases, and permit a comparison of the active sites of enzymes that reduce 2MPN with either R or S selectivity.

DERIVATIVES OF [1, 2, 4] TRIAZOLO [4, 3 - A] PYRIDINE AS P38 - MAP KINASE INHIBITORS

This invention relates to compounds selected in the group consisting of compounds of formula (la) to (Id) and compositions, that are p38 MAPK inhibitors, useful as anti-inflammatory agents in the treatment of, inter alia, diseases of the respiratory tract.

KINASE INHIBITORS

Compounds of formula (I) described herein are p38 MAPK inhibitors and are useful as anti-inflammatory agents in the treatment of, inter alia, diseases of the respiratory tract