477600-69-4

Usage

Uses

Used in Pharmaceutical Industry:
(3S,4S)-1-Benzyl-N,4-dimethylpiperidin-3-amine is used as a reagent for the preparation of substituted pyrrolopyrimidinamines, specifically as Janus kinase (JAK) inhibitors. These inhibitors, such as CP-352,664, are being developed for the treatment of autoimmune diseases and organ transplant rejection. (3S,4S)-1-Benzyl-N,4-dimethylpiperidin-3-amine's ability to modulate JAK activity makes it a valuable tool in the development of therapeutics for these conditions.

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+/m0/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 
• 32018-96-5 1-benzyl-4-methyl-piperidin-3-one 
• 6998-30-7 methylamine acetate 
• 1062580-52-2 N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride 
• 108-89-4 picoline 
• 3430-22-6 3-Bromo-4-methylpyridin 
• 1615709-89-1 1-benzyl-4-methyl-3-(methylamino)pyridinium bromide 
• 1092578-35-2 tert-butyl (3R,4S)-1-benzyl-4-methylpiperidin-3-ylcarbamate 
• 100-46-9 benzylamine 
• 74-89-5 methylamine 
• 384338-20-9 (3R,4R)-1-benzyl-4-methylpiperidin-3-ol 
• 384338-20-9 1-benzyl-4-methylpiperidin-3-ol 
• 1548270-19-4 1-benzyl-4-methyl-3-(methylamino)piperidin-4-ol 

Downstream Products

• 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 academic research and scientific papers

Synthesis method of tofacitinib citrate diastereomer impurities

The invention discloses a synthesis method of tofacitinib citrate diastereomer impurities, relates to the technical field of drug organic synthesis, and relates to 3 - amino -4 - methylpyridine as a starting material and a quaternary ammonium salt. Raw materials of the whole synthetic route are easily available, the reaction conditions are mild, the post-treatment separation and purification operation is simple and feasible, and the preparation method is good in repeatability.

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 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.

Preparation method and application of chiral amine B

The invention discloses a preparation method of chiral amine B. The preparation method comprises the following steps: (1) carrying out nucleophilic substitution reaction on N-tert-butoxycarbonyl-3-pyridine and halogenated benzyl to obtain an intermediate

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.

Preparing method of N-methyl-N-(4-methylpiperidine)-3-yl-7H-pyrropyrimidine-4-amine

The invention relates to a novel synthesis route of N-methyl-N-(4-methylpiperidine)-3-yl-7H-pyrropyrimidine-4-amine. According to the synthesis route, 4-methyl-3-piperidone and 4-hydroxyl-6,7-dihydro-5H-pyrrolo[2,3-D]pyrimidine are taken as raw materials separately, and a key tofacitinib intermediate, namely N-methyl-N-((3R,4R)-4-methylpiperidine-3-yl)-7H-pyrrolo[2,3D]pyrimidine-4-amine with highyield is synthesized through six-step reactions. The preparing method of the key tofacitinib intermediate, namely the N-methyl-N-((3R,4R)-4-methylpiperidine-3-yl)-7H-pyrrolo[2,3D]pyrimidine-4-amine has the advantages of being high in yield, high in chiral purity, low in cost, environmentally friendly, easy to operate and suitable for industrialization.

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.

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.

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.