477600-70-7

Basic information

• Product Name: (3R,4R)-1-Benzyl-N,4-dimethylpiperidin-3-amine
• Synonyms: (3R,4R)-1-Benzyl-N,4-dimethylpiperidin-3-amine;(Cis)-Benzyl-N,4-diMethylpiperidin-3-aMine;(3R,4R)-1-benzyl-N,4-diMethylpiperidin-3-aMine hydrochloride;3-PiperidinaMine, N,4-diMethyl-1-(phenylMethyl)-, (3R,4R)-;(3R,4R)-(1-benzyl-4-Methylpiperidin-3-yl)MethylaMine;(3R,4R)-1-Benzyl-N,4-diMe...;(3R,4R)-1-Benzyl-N-Methyl-4-Methylpiperidin-3-aMine;(3R,4R)-1-BENYL-N,4-DIMETHYLPIPERIDIN-3-AMINE
• CAS NO: 477600-70-7
• Molecular Formula: C₁₄H₂₂N₂
• Molecular Weight: 218.33788
• Mol File: 477600-70-7.mol

Chemical Properties

• Boiling Point: 302.6°Cat760mmHg
• Flash Point: 107.4°C
• Appearance: /
• Density: 1g/cm³
• Vapor Pressure: 0.000978mmHg at 25°C
• Refractive Index: 1.547
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• PKA: 10.26±0.40(Predicted)
• CAS DataBase Reference: (3R,4R)-1-Benzyl-N,4-dimethylpiperidin-3-amine(CAS DataBase Reference)
• NIST Chemistry Reference: (3R,4R)-1-Benzyl-N,4-dimethylpiperidin-3-amine(477600-70-7)
• EPA Substance Registry System: (3R,4R)-1-Benzyl-N,4-dimethylpiperidin-3-amine(477600-70-7)

Safety Data

• Hazardous Substances Data: 477600-70-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(3R,4R)-1-Benzyl-N,4-dimethylpiperidin-3-amine is used as a reagent for the preparation of Janus tyrosine kinase inhibitors. These inhibitors are crucial in the treatment of autoimmune diseases, as they help regulate the immune system and prevent it from attacking the body's own cells.
Used in Autoimmune Disease Treatment:
(3R,4R)-1-Benzyl-N,4-dimethylpiperidin-3-amine is used as a key component in the development of drugs that target Janus tyrosine kinases. By inhibiting these enzymes, the compound can help manage and treat various autoimmune diseases, such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease, among others. (3R,4R)-1-Benzyl-N,4-dimethylpiperidin-3-amine's role in the development of these drugs is to provide a structural framework that can be further modified and optimized for therapeutic use.

InChI:InChI=1/C14H22N2/c1-12-8-9-16(11-14(12)15-2)10-13-6-4-3-5-7-13/h3-7,12,14-15H,8-11H2,1-2H3/t12-,14+/m1/s1

Upstream product

• 923036-28-6 (1-benzyl-4-methyl-1,2,5,6-tetrahydropyridin-3-yl)carbamic acid methyl ester 
• 923036-27-5 1-benzyl-3-methoxycarbonylamino-4-methyl-pyridinium bromide 
• 100-46-9 benzylamine 
• 74-89-5 methylamine 
• 32018-96-5 1-benzyl-4-methyl-piperidin-3-one 
• 6998-30-7 methylamine acetate 
• 1092578-34-1 tert-butyl (3R,4R)-1-benzyl-4-methylpiperidin-3-ylcarbamate 
• 68085-43-8 2-cyano-3-methylglutarimide 
• 77303-35-6 4-methyl-2,6-dioxo-1,2,5,6-tetrahydro-pyridine-3-carbonitrile 
• 384338-23-2 (1-benzyl-4-methyl-piperidin-3-yl)-methyl-amine 
• 384338-20-9 1-benzyl-4-methylpiperidin-3-ol 
• 1062580-52-2 N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride 

Downstream Products

• 894360-25-9 N-[(3R,4R)-1-benzyl-4-methylpiperidin-3-yl]-N-methyl-1-[2-(trimethylsilyl)-ethoxy]methyl-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine 
• 920965-88-4 4-N-[(3R,4R)-1-benzyl-4-methylpiperidin-3-yl]-4-N-methyl-3-nitropyridine-2,4-diamine 
• 923036-30-0 N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methyl-(7-p-toluenesulfonyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine 
• 1263419-12-0 4-(((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)(methyl)amino)pyrrolo[1,2-b]pyridazine-3-carbonitrile 
• 1206824-89-6 tert-butyl N-methyl-N-[(3R,4R)-4-methylpiperidin-3-yl]carbamate 
• 1640971-60-3 3-[(3R,4R)-3-[(6-aminopyrimidin-4-yl)(methyl)amino]-4-methylpiperidin-1-yl]-3-oxopropanenitrile 
• 477600-74-1 tert-butyl (3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidine-1-carboxylate 
• 1259404-17-5 tasocitinib 
• 920965-91-9 N⁴-[(3R,4R)-1-benzyl-4-methyl-3-piperidinyl]-N⁴-methyl-2,3,4-pyridinetriamine 
• 1616761-00-2 3-[(3R,4R)-3-({2-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl}(methyl)amino)-4-methylpiperidin-1-yl]-3-oxopropanenitrile 

Relevant articles and documents

Preparation methods of tofacitinib intermediate amine and dihydrochloride thereof

The invention discloses preparation methods of tofacitinib intermediate amine and dihydrochloride thereof. According to the preparation method of the tofacitinib intermediate amine, methyl acetoacetate and cyanoacetamide are taken as starting materials and subjected to condensation, olefinic bond reduction, cyano hydrolysis into amide, N benzylation and Hofmann degradation to prepare primary amine, monomethylation and chiral resolution of the primary amine are performed, and a carbonyl group is reduced with zinc borohydride, so a target product is obtained. The obtained (3R,4R)-1-benzyl-3-methylamino-4-methylpiperidine is subjected to salifying with hydrochloric acid to obtain the dihydrochloride. The methods have the advantages that the whole process avoids a high-pressure hydrogenation reaction under an acidic condition; all the reaction steps adopt conventional reaction reagents and solvents, so raw material sources are not limited, and cost is low; and the method avoids a lithium aluminum hydride reduction reagent with high risk, each step has high selectivity, the reaction product of each step can be easily refined, and the method has advantages in industrialization.

Novel method for preparing 3-amino-piperidine

The present invention relates to a manufacturing method which is capable of mass production of (3R,4R)-(1-benzyl-4-methylpiperidin-3-yl)-methylamine on an industrial scale with high quality optical purity, which is a key intermediate necessary for synthesizing tofacitinib.

PROCESS FOR THE PREPARATION OF CHIRAL 3-AMINO-PIPERIDINS, USEFUL INTERMEDIATES FOR THE PREPARATION OF TOFACITINIB

Object of the present invention is an improved process for the preparation of (3R,4R)-1-benzyl-4-methylpiperidin-3-amine by means of chiral Rhodium catalysts.

Preparation method for chiral piperylhydrazine compound and recycling method for chiral resolving agent

The invention discloses a preparation method for a chiral piperylhydrazine compound and a recycling method for a chiral resolving agent. In the invention, 1-benzyl-4-methyl-3-pipradrol is taken as aninitial raw material and is subjected to reactions of halogenation, methylamination, chiral resolution, and the like, so as to prepare a (3R, 4R)-N,4-dimethyl-1-(phenyl methyl)-3-piperylhydrazine dihydrochloride product, and meanwhile, a resolving mother solution is subjected to alkalization, refined, purified and recycled, so as to acquire a (2R,3R)-2,3-bi[(4-methyl benzoyl) oxo] succinic acid product meeting the reaction requirement. The invention has the beneficial effects of 1) short synthetic route, easily controlled intermediate purity and benefit to the control on impurity content, and2) simple and convenient technological operation in each step reaction, capability of recycling the high-dosage chiral resolving agent, capability of reducing production cost while reducing yield of solid wastes and suitability for large-scale industrial production.

Synthesis method of tofacitinib intermediate (3R, 4R)-1-benzyl-N,4-dimethylpiperidine-3-amine

The invention discloses a synthesis method of a tofacitinib intermediate (3R, 4R)-1-benzyl-N,4-dimethylpiperidine-3-amine. The synthesis method comprises the steps: making 3-chlorobutyraldehyde (II) serving as a raw material react with sodium cyanide, then, carrying out Leuckart-Wallach reaction and a Thorpe-Ziegler reaction, next, reacting with a 30% methylamine methanol solution to generate enamine, and carrying out asymmetric catalytic hydrogenation to obtain a final product (3R, 4R)-1-benzyl-N,4-dimethylpiperidine-3-amine (I). In the synthesis method, a compound VI is synthesized by a Thorpe-Ziegler reaction, and the yield is high; and due to the adoption of the asymmetric catalytic hydrogenation, the final product is not needed to be subjected to chiral resolution, the total yield andpurity are high, and few byproducts are generated.

Asymmetric Synthesis of a Key Intermediate for Tofacitinib via a Dynamic Kinetic Resolution-Reductive Amination Protocol

We report the first example of a catalytic asymmetric reductive amination under dynamic kinetic resolution (DKR) conditions for the preparation of a chiral amine as a key intermediate toward Tofacitinib, an active pharmaceutical ingredient developed by Pfizer. Such a protocol allows the preferential formation of a single product out of four possible diastereomers of the chiral amine starting from the corresponding racemic ketone. The chiral iridium catalyst able to perform such a feast was discovered through a mix of high-throughput screening, racemization study, and reaction optimization.

Novel method for synthesizing cis-1-benzyl-3-methylamino-4-methyl-piperidine

The invention provides a novel method for synthesizing cis-1-benzyl-3-methylamino-4-methyl-piperidine. The method has the advantages that aminopyridine is used as the raw material, the original two-step arylamine methylation becomes one-step reaction, unfriendly lithium aluminum hydrogen reduction is avoided, toxic controlled product methyl chloroformate is avoided, the used raw materials are simple and easy to obtain, the method is suitable for industrial production, the generation of a large amount of aluminum-containing wastewater is reduced, production cycle is shortened evidently, and productivity is increased.

PROCESS FOR PREPARING CHIRAL AMINES

The invention pertains to a process for the preparation of an amine having at least two chiral centers from a ketone having a chiral center at the a position and an amine comprising the steps of: (a) contacting a ketone having a chiral center at the a position and a primary amine thereby forming an imine; (b) contacting the imine with a reducing agent in the presence of an enantioselective catalyst to form an amine having at least two chiral centers, wherein step (a) and/or step (b) are conducted under racemization-enhancing conditions, wherein the racemization-enhancing conditions are achieved by addition of an acid and/or by addition of a salt of a primary amine and an acid, which salt is added in addition to or instead of the primary amine, and wherein the reducing agent is hydrogen.

Formal asymmetric synthesis of (+)-tofacitinib

Tofacitinib is an efficient and selective Janus kinase 3 (JAK3) inhibitor, and is used as an immunosuppressant drug for the treatment of rheumatoid arthritis and transplant patients. Herein we report a concise formal asymmetric synthesis of tofacitinib from homochiral 1,3-dioxolanone 10b, which was elaborated through a highly stereoselective Michael addition followed by solvent-free removal of the chiral auxiliary and ring cyclization to furnish chiral imide 8. The preparation of tofacitinib's precursor 16 could be obtained after reduction of 8 followed by sequential oxidation, reductive amination and SNAr reactions.

Examining the chirality, conformation and selective kinase inhibition of 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino) piperidin-1-yl)-3-oxopropanenitrile (CP-690,550)

Here, we examine the significance that stereochemistry plays within the clinically relevant Janus kinase 3 (Jak3) inhibitor 1 (CP-690,550). A synthesis of all four enantiopure stereoisomers of the drug was carried out and an examination of each compound revealed that only the enantiopure 3R,4R isomer was capable of blocking Stat5 phosphorylation (Jak3 dependent). Each compound was profiled across a panel of over 350 kinases, which revealed a high level of selectivity for the Jak family kinases for these related compounds. Each stereoisomer retained a degree of binding to Jak3 and Jak2 and the 3R,4S and 3S,4R stereoisomers were further revealed to have binding affinity for selected members of the STE7 and STE20 subfamily of kinases. Finally, an appraisal of the minimum energy conformation of each stereoisomer and molecular docking at Jak3 was performed in an effort to better understand each compounds selectivity and potency profiles.