1260590-51-9

Basic information

• Product Name: N-Methyl-N-((3R,4R)-4-Methylpiperidin-3-yl)-7H-pyrrolo[2,3-d]pyriMidin-4-aMine dihydrochloride
• Synonyms: N-Methyl-N-((3R,4R)-4-Methylpiperidin-3-yl)-7H-pyrrolo[2,3-d]pyriMidin-4-aMine dihydrochloride;N-Methyl-N-((3R,4R)-4-Methylpiperidin-3-yl)-7H-pyrrolo[2,3-d]pyriMidin-4-amine dihydrochloride (N-1 HCl);N-Methyl-N-[(3R,4R)-4-methyl-3-piperidyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine x hydrochloride;-4-methylpiperidin-3-yl);N-Methyl-N-((3R,4R);N-METHYL-N-((3R,4R)-4-METHYLPIPERIDIN-3-YL)-7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE HCL
• CAS NO: 1260590-51-9
• Molecular Formula: C13H21Cl2N5
• Molecular Weight: 318.24534
• Mol File: 1260590-51-9.mol

Chemical Properties

• Appearance: /
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility: Aqueous Acid (Slightly, Sonicated), Aqueous Base (Slightly), Water (Slightly)
• CAS DataBase Reference: N-Methyl-N-((3R,4R)-4-Methylpiperidin-3-yl)-7H-pyrrolo[2,3-d]pyriMidin-4-aMine dihydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: N-Methyl-N-((3R,4R)-4-Methylpiperidin-3-yl)-7H-pyrrolo[2,3-d]pyriMidin-4-aMine dihydrochloride(1260590-51-9)
• EPA Substance Registry System: N-Methyl-N-((3R,4R)-4-Methylpiperidin-3-yl)-7H-pyrrolo[2,3-d]pyriMidin-4-aMine dihydrochloride(1260590-51-9)

Safety Data

• Hazardous Substances Data: 1260590-51-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
N-Methyl-N-((3R,4R)-4-Methylpiperidin-3-yl)-7H-pyrrolo[2,3-d]pyriMidin-4-aMine dihydrochloride is used as a reagent for the synthesis of Tofacitinib (CP-690,550), a Janus tyrosine kinase (JAK3) specific inhibitor, which is an important drug for treating various inflammatory and autoimmune diseases.
Used in Quality Assurance and Process Monitoring:
N-Methyl-N-((3R,4R)-4-Methylpiperidin-3-yl)-7H-pyrrolo[2,3-d]pyriMidin-4-aMine dihydrochloride is used as a substance in the identification of related substances in the degradation products of tofacitinib citrate. This application is crucial for process monitoring and quality assurance in the pharmaceutical industry, as it helps ensure the safety, efficacy, and purity of the final drug product by employing the LC-MS technique.

Synthesis

Add TFTB-1, sodium hydroxide, ethanol and water to a 20L reaction flask, heat to 85 ° C, and keep the reaction for 3 hours. At the end of the reaction, vacuum distillation at 80-90 ° C until no liquid flows out. Add purified water and continue stirring. The mixture was cooled to room temperature, extracted with dichloromethane, and the aqueous layer was extracted with methylene chloride. The organic layer was combined, and the organic layer was washed with purified water. Filtration, evaporation of the filtrate, addition of acetone, reflux for 30 min, cooling to 20 ° C, filtration, filter cake into a dry box, drying at 60 ° C ± 5 ° C for 4 h, to obtain a white solid, that is, TFTB-2, yield 86%.

Upstream product

• 1121-19-3 4-methylpyridin-3-ol 
• 374794-77-1 tert-butyl 4-methyl-3-oxopiperidine-1-carboxylate 
• 1312762-44-9 (3R,4R)-3-methylamino-4-methylpiperidine-1-carboxylic acid tert-butyl ester 
• 1062580-52-2 N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride 
• 479633-63-1 4-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidine 
• 3680-69-1 4-chloro-1H-pyrrolo[2,3-d]pyrimidine 
• 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 
• 923036-25-3 (3R,4R)-(1-benzyl-4-methylpiperidin-3-yl)-2-chloro-N-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amine 

Downstream Products

• 1259404-17-5 tasocitinib 
• 540737-29-9 Tofacitinib citrate 

Relevant articles and documents

Preparation method of tofacitinib intermediate

The invention belongs to the field of pharmaceutical chemicals, and relates to a preparation method of a tofacitinib intermediate. According to the preparation method, in the process of preparing a compound shown as a formula II from a compound shown as a

Preparation method of tofacitinib citrate intermediate

The invention provides a preparation method of a citric acid tofacitinib intermediate, and particularly provides a preparation method of a citric acid tofacitinib intermediate N-methyl-N-((3R, 4R)-4-methylpiperidine-3-yl)-N-methyl-7H-pyrrole [2, 3-d] pyrimidine-4-amine hydrochloride, which is characterized in that a reaction is carried out in a microchannel reactor, the intermediate can be obtained with very high yield and purity, and has good industrial application value.

Tofacitinib citrate intermediate as well as preparation method and application thereof

The invention belongs to the technical field of medicinal chemistry, and particularly relates to a tofacitinib citrate intermediate as well as a preparation method and an application thereof. Whereinthe tofacitinib citrate intermediate is N-methyl-N-((3R, 4R)-4-methylpiperidine-3-yl)-7H-pyrrolo [2, 3-D] pyrimidine-4-amine dihydrochloride monohydrate. The preparation method comprises the followingsteps: adding N-methyl-N-((3R, 4R)-1-benzyl-4-methylpiperidine-3-yl)-N-methyl-7H-pyrrolo [2, 3-d] pyrimidine-4-amine into water and an organic solvent, then adding hydrochloric acid and palladium hydroxide carbon, introducing hydrogen to react, and filtering out the palladium hydroxide carbon; cooling to room temperature, dropwise adding an organic solvent, crystallizing, carrying out suction filtration, and drying to obtain the tofacitinib citrate intermediate. The method greatly improves the utilization rate of raw materials, reduces the production cost, and improves the product quality.

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.

Synthetic method for compound

The invention provides a synthetic method for a compound having a structural formula represented by a formula (V) shown in the specification. The method comprises the following steps: 1) performing hydrodebenzylation on a compound having a structural formula represented by a formula (I) shown in the specification to obtain a compound having a structural formula represented by a formula (II) shownin the specification; 2) allowing a compound having a structural formula represented by a formula (III) to be in contact with the compound having the structural formula represented by the formula (II)to obtain a compound having a structural formula represented by a formula (IV) shown in the specification; and 3) allowing the compound having the structural formula represented by the formula (IV) to be in contact with an acid solution to remove t-butoxycarbonyl protection, so as to obtain the compound having the structural formula represented by the formula (V). The synthetic method provided bythe invention has the advantages of a short synthetic route, a simple process, easy availability of the raw materials, simple post-treatment, good quality and a high yield, and is suitable for industrial production of tasocitinib and an intermediate of the tasocitinib.

Preparation method for tofacitinib citrate

The invention relates to the field of medicinal chemistry, and provides a preparation method for tofacitinib. ((3R,4R)-1-benzyl-4-methyl-piperidine-3-radical)-methyl-(7H-pyrrolo [2, 3-D] pyrimidine-4-radical)-amine is taken as a starting material, after the hydrogenation debenzylation reaction and amidation, tofacitinib is prepared, and after the tofacitinib and citric acid are salified, the tofacitinib citrate is obtained. According to the developed technology, the product quality is quite high, the purity is 99.9% or above, the content of any individual impurity is less than 0.1%, and the quality standard of tofacitinib citrate medicine as a registered active pharmaceutical ingredient is met. The hydrogenation reaction utilizes an aqueous hydrochloric acid solution as a solvent, and thehydrogenation reaction is quite safe, green and environmentally friendly.

A tofacitinib citrate purification method

The invention belongs to the field of medicine synthesis and provides a tofacitinib citrate purification method which can effectively remove an impurity G. The method includes adding a tofacitinib citrate crude product to be purified into a mixed solvent, stirring and heating the mixture until the crude product is fully dissolved, cooling the mixture for crystallization, and performing filtrationand vacuum drying to obtain a purified tofacitinib citrate product. The method is simple to operate and suitable for industrial scale-up production, and has obvious impurity removing effects and a high yield.

Industrial production method of citric acid tofacitinib

The invention discloses an industrial production method of citric acid tofacitinib. The method comprises the following steps: (1) adding a compound SMA and a compound SMB to a mixed solvent 1 which comprises DMSO and purified water, and catalyzing through

A method for synthesis of piperidine derivatives (by machine translation)

The invention discloses a method for synthesis of piperidine derivatives. The piperidine derivatives of the formula (I) of the tartrate: Wherein R1 Is an amino protecting group, R2 Is phenyl or alkyl substituted phenyl, R3 Is C1 - C6 alkyl; by the piperidine derivative having the structural formula (II) with a compound L - tartaric acid reaction, then the obtained through separation, In the having piperidine 3 bit reference into the S on amino-substituted radical, can significantly improve the for tartaric acid from L - In the separate The effect of the. The method can be used for the synthesis of pharmaceutical Tofacitinib, in order to improve the yield of drug Tofacitinib. (by machine translation)