384338-23-2

Basic information

• Product Name: 1-BENZYL-N,4-DIMETHYLPIPERIDIN-3-AMINE DIHYDROCHLORIDE
• Synonyms: (1-Benzyl-4-Methylpiperidin-3-yl)MethylaMine or dihydrochloride;raceMic Mixture tofacitinib interMediat;Tofacitinib IMpurity F;N,4-dimethyl-1-(phenylmethyl)-3-Piperidinamine;1-BENZYL-N,4-DIMETHYLPIPERIDIN-3-AMINE DIHYDROCHLORIDE;3-PiperidinaMine, N,4-diMethyl-1-(phenylMethyl)-;(1-Benzyl-4-methylpiperidin-3-yl)methylamine;1-Benzyl-N-methyl-4-methylpiperidin-3-amine
• CAS NO: 384338-23-2
• Molecular Formula: C₁₄H₂₂N₂
• Molecular Weight: 291.25976
• Mol File: 384338-23-2.mol

Chemical Properties

• Appearance: /
• CAS DataBase Reference: 1-BENZYL-N,4-DIMETHYLPIPERIDIN-3-AMINE DIHYDROCHLORIDE(CAS DataBase Reference)
• NIST Chemistry Reference: 1-BENZYL-N,4-DIMETHYLPIPERIDIN-3-AMINE DIHYDROCHLORIDE(384338-23-2)
• EPA Substance Registry System: 1-BENZYL-N,4-DIMETHYLPIPERIDIN-3-AMINE DIHYDROCHLORIDE(384338-23-2)

Safety Data

• Hazardous Substances Data: 384338-23-2(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
1-BENZYL-N,4-DIMETHYLPIPERIDIN-3-AMINE DIHYDROCHLORIDE is used as an impurity in the development of Tofaritinib, a Janus kinase inhibitor, for the treatment of rheumatoid arthritis. Its presence in Tofaritinib is crucial for understanding the drug's efficacy and safety profile, as well as for quality control purposes in the pharmaceutical manufacturing process.

Upstream product

• 32018-96-5 1-benzyl-4-methyl-piperidin-3-one 
• 74-89-5 methylamine 
• 1206875-41-3 cis-(1-Benzyl-4-methyl-piperidin-3-yl)-carbamic Acid Methyl Ester 
• 1548270-31-0 1-benzyl-3-bromo-4-methylpiperidin-4-ol 
• 32018-56-7 1-benzyl-4-methyl-1 ,2,3,6-tetrahydropyridine 
• 1548270-41-2 C₁₄H₂₀N₂ 
• 1548270-43-4 C₁₄H₂₀N₂ 
• 1548270-19-4 1-benzyl-4-methyl-3-(methylamino)piperidin-4-ol 
• 107-31-3 Methyl formate 
• 1039738-27-6 1-benzyl-4-methyl-3-amino piperidine 
• 108-89-4 picoline 
• 3430-22-6 3-Bromo-4-methylpyridin 
• 1615709-89-1 1-benzyl-4-methyl-3-(methylamino)pyridinium bromide 
• 593-51-1 methylamine hydrochloride 

Downstream Products

• 384337-90-0 methyl(1-phenylmethyl-4-methylpiperidin-3-yl)-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine 
• 1252883-87-6 N-(1-benzyl-4-methylpiperidin-3-yl)-N-methyl-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine 
• 384336-73-6 (3R,4R)-methyl-(4-methyl-piperidin-3-yl)-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine 
• 1259404-17-5 tasocitinib 
• 540737-29-9 Tofacitinib citrate 
• 1062580-52-2 N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride 
• 1228879-37-5 (3R,4R)-1-benzyl-N,4-dimethylpiperidine-3-amine dihydrochloride 
• 477600-70-7 N-(3R,4R)-(1-benzyl-4-methylpiperidin-3-yl)-methylamine 

Relevant articles and documents

Preparation methods of tofacitinib citrate intermediate and tofacitinib citrate

The invention discloses preparation methods of a tofacitinib citrate intermediate and tofacitinib citrate. The preparation method of the tofacitinib citrate intermediate comprises: preparing N-(1-benzyl-4-methyl-1,2,5,6-tetrahydropiperidine-3-yl)acetamide by using 3-amino-4-methyl-pyridine, acetyl chloride, benzyl chloride and sodium borohydride as raw materials; preparing 1-benzyl-N,4-dimethylpiperidine-3-amine by using the N-(1-benzyl-4-methyl-1,2,5,6-tetrahydropiperidine-3-yl)acetamide, hydrochloric acid, methylamine and sodium borohydride as raw materials; and carrying out resolution and dissociation on the 1-benzyl-N,4-dimethylpiperidine-3-amine, and carrying out salt forming with hydrochloric acid to obtain the product. The invention provides the new tofacitinib citrate intermediatepreparation method, wherein the use amount of the catalytic hydrogenation catalyst is reduced in the preparation process of tofacitinib citrate so as to reduce the cost, and the generation of N-alkylated impurities can be well controlled by adopting the isopropanol/water mixed solvent.

Preparation method for 1-benzyl-N,4-dimethylpiperidin-3-amine

The invention provides a preparation method for 1-benzyl-N,4-dimethylpiperidin-3-amine. The preparation method comprises the following steps: (1) reacting a compound N,4-dimethylpyridin-3-methylamineas shown in a formula (I) with dimethyl dicarbonate under basic conditions to obtain a compound as shown in a formula (II); (2) reacting the compound as shown in the formula (II) with benzyl chlorideto obtain a compound as shown in a formula (III); (3) reducing the compound as shown in the formula (III) to synthesize to a compound as shown in a formula (IV); and (4) subjecting the compound as shown in the formula (III) to a reaction under the action of lithium aluminum hydride to form the target product 1-benzyl-N,4-dimethylpiperidin-3-amine. The preparation method for 1-benzyl-N,4-dimethylpiperidin-3-amine in the invention has the advantages of easy availability of raw materials, environment-friendly reaction conditions in each step, simple operation and high yield.

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.

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.

AN IMPROVED PROCESS FOR THE PREPARATION OF (3R,4R)-(1-BENZYL-4-METHYLPIPERIDIN-3-YL)-METHYLAMINE

The present invention is related to an improved and efficient process for preparation of (3R,4R)-(1-benzyl-4-methylpiperidin-3-yl)-methylamine which comprises: (a) N-acylation of 3-Amino-4-methyl pyridine; (b) Quarternization of 3-Acetylamino-4- methyl pyridine using benzyl halide; (c) Partial reduction of quarternized 3-Acetylamino- 4-methyl pyridine by Sodium borohydride in Methanol or water; (d) Hydrolysis of partially reduced product to 1-Benzyl-4-methylpiperidin-3-one in presence of acid; (e) Reductive animation of 1-Benzyl-4-methylpiperidin-3-one using Methanolic methylamine in presence of Titanium(IV) isopropoxide in Methanol; (f) Resolution of 1-Benzyl-4- methylpiperidin-3-yl)-methylamine using Ditoluoyl (L) tartaric acid to get (3R,4R)-(1- benzyl-4-methylpiperidin-3-yl)-methylamine. The invention is also related to novel intermediates.

PROCESS FOR THE PREPARATION OF TOFACITINIB AND INTERMEDIATES THEREOF

The present invention provides compounds of Formula III and Formula VI, and processes for their preparation. The present invention further provides use of the compounds of Formula III and Formula VI for the preparation of tofacitinib or isomers or a mixture of isomers or salts thereof.

PREPARATION OF 3-AMINO-PIPERIDINE COMPOUNDS VIA NITRO-TETRAHYDROPYRIDINE PRECURSORS

The present invention relates to the preparation of 3-amino-piperidine compounds via nitro-tetrahydropyridine precursors and salts thereof. These compounds can be used as intermediates in the synthesis of pharmaceutically active agents such as tofacitinib or derivatives thereof.

NEW SYNTHETIC ROUTE FOR THE PREPARATION OF 3-AMINO-PIPERIDINE COMPOUNDS

The present invention relates in general to the field of organic chemistry and in particular to the preparation of 3-amino-piperidine compounds. These compounds can be used as intermediates in the synthesis of pharmaceutically active agents such as preferably tofacitinib or derivatives thereof, or further pharmaceutically active agents comprising as a structure a 3-aminopiperidine moiety.

PHARMACEUTICAL COMPOSITIONS AND METHODS OF TREATING DRY EYE DISORDERS

Ophthalmic compositions comprising Inhibitors of Janus kinase-3 (“Jak3”) are useful for treating dry eye disorders and other disorders requiring the wetting of the eye.

PIPERIDINE INHIBITORS OF JANUS KINASE 3

The present invention relates to a new piperidine inhibitors of Janus Kinase 3 activity, pharmaceutical compositions thereof, and methods of use there-of.