923036-30-0

Basic information

• Product Name: 7H-Pyrrolo[2,3-d]pyriMidin-4-aMine, N-Methyl-N-[(3R,4R)-4-Methyl-1-(phenylMethyl)-3-piperidinyl]-7-[(4-Met hylphenyl)sulfonyl]-
• Synonyms: Tofacitinib Impurity 17;7H-Pyrrolo[2,3-d]pyriMidin-4-aMine, N-Methyl-N-[(3R,4R)-4-Methyl-1-(phenylMethyl)-3-piperidinyl]-7-[(4-Met hylphenyl)sulfonyl]-;N-Methyl-N-[(3R,4R)-4-methyl-1-(phenylmethyl)-3-piperidinyl]-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine
• CAS NO: 923036-30-0
• Molecular Formula: C₂₇H₃₁N₅O₂S
• Molecular Weight: 489.63234
• Mol File: 923036-30-0.mol

Chemical Properties

• Melting Point: 180-183℃
• Boiling Point: 655.2±65.0 °C(Predicted)
• Appearance: /
• Density: 1.27±0.1 g/cm3(Predicted)
• Storage Temp.: 2-8°C
• PKA: 9.02±0.10(Predicted)
• CAS DataBase Reference: 7H-Pyrrolo[2,3-d]pyriMidin-4-aMine, N-Methyl-N-[(3R,4R)-4-Methyl-1-(phenylMethyl)-3-piperidinyl]-7-[(4-Met hylphenyl)sulfonyl]-(CAS DataBase Reference)
• NIST Chemistry Reference: 7H-Pyrrolo[2,3-d]pyriMidin-4-aMine, N-Methyl-N-[(3R,4R)-4-Methyl-1-(phenylMethyl)-3-piperidinyl]-7-[(4-Met hylphenyl)sulfonyl]-(923036-30-0)
• EPA Substance Registry System: 7H-Pyrrolo[2,3-d]pyriMidin-4-aMine, N-Methyl-N-[(3R,4R)-4-Methyl-1-(phenylMethyl)-3-piperidinyl]-7-[(4-Met hylphenyl)sulfonyl]-(923036-30-0)

Safety Data

• Hazardous Substances Data: 923036-30-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
7H-Pyrrolo[2,3-d]pyrimidin-4-amine, N-Methyl-N-[(3R,4R)-4-Methyl-1-(phenylMethyl)-3-piperidinyl]-7-[(4-Methylphenyl)sulfonyl]is used as a useful intermediate for the formal asymmetric synthesis of (+)-?-Tofacitinib. Tofacitinib is a medication used to treat rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis. 7H-Pyrrolo[2,3-d]pyriMidin-4-aMine, N-Methyl-N-[(3R,4R)-4-Methyl-1-(phenylMethyl)-3-piperidinyl]-7-[(4-Met hylphenyl)sulfonyl]plays a crucial role in the development and production of this important drug.
Used in Quality Control and Impurity Testing:
7H-Pyrrolo[2,3-d]pyrimidin-4-amine, N-Methyl-N-[(3R,4R)-4-Methyl-1-(phenylMethyl)-3-piperidinyl]-7-[(4-Methylphenyl)sulfonyl]is also an impurity of Tofacitinib (C781351). It is essential to monitor and control the presence of this impurity in the final drug product to ensure its safety, efficacy, and quality. 7H-Pyrrolo[2,3-d]pyriMidin-4-aMine, N-Methyl-N-[(3R,4R)-4-Methyl-1-(phenylMethyl)-3-piperidinyl]-7-[(4-Met hylphenyl)sulfonyl]is used in quality control processes and impurity testing to maintain the desired standards of the pharmaceutical product.

Upstream product

• 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 
• 98-59-9 p-toluenesulfonyl chloride 
• 384338-20-9 (3S,4R)-1-benzyl-4-methylpiperidin-3-ol 
• 74-88-4 methyl iodide 
• 100-44-7 benzyl chloride 
• 1062580-52-2 N-((3R,4R)-1-benzyl-4-methylpiperidin-3-yl)-N-methylamine dihydrochloride 
• 3430-27-1 3-amino-4-methylpyridine 
• 1354621-59-2 C₁₄H₂₂N₂ 
• 384338-20-9 (3R,4R)-1-benzyl-4-methylpiperidin-3-ol 
• 100-46-9 benzylamine 
• 477600-70-7 N-(3R,4R)-(1-benzyl-4-methylpiperidin-3-yl)-methylamine 

Downstream Products

• 1259404-17-5 tasocitinib 
• 477600-74-1 tert-butyl (3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidine-1-carboxylate 
• 540737-29-9 tofacitinib citrate 
• 1260590-51-9 ((3R,4R)-4-methylpiperidin-3-yl)-N-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amine dihydrochloride 
• 540737-29-9 Tofacitinib citrate 

Relevant articles and documents

Synthesis method of tofacitinib citrate

The invention discloses a tofacitinib citrate synthesis method, belongs to the technical field of tofacitinib citrate preparation, and can effectively inhibit activity of Janus and JAK1 JAK3, block signal transduction of various inflammatory cytokines, and has an expensive catalyst application in the existing synthesis step. The method uses 1 - benzyl -4 - methyl -3 - (methylamino) piperidine hydrochloride as a raw material to prepare the tofacitinib citrate as a raw material, and then the citric acid tofacitinib citrate is obtained through twice refining 4 -7 - and the - 7H - yield and 2 the 3 - D purity of the tofacitinib citrate are improved.

Process for the preparation of tofacitinib and intermediates thereof

Provided is a process for the preparation of high purity tofacitinib, which reduces formation of N-methyl impurity. The invention also provides novel intermediates used in the process to prepare tofacitinib. There is provided an improved process for the preparation of tofacitinib (I), comprising the steps of: adding cyanoacetic acid in molar equivalent 0.2-1.2 to compound of formula (II-S), followed by addition of carbodiimide coupling agent of formula (III), optionally reacting tofacitinib base with citric acid.

PROCESS FOR PREPARATION OF TOFACITINIB AND PHARMACEUTICALLY ACCEPTABLE SALT THEREOF

The present invention relates to an improved process for preparation of tofacitinib (I) and pharmaceutically acceptable salt thereof. (I)

Preparation method of tofacitinib or salt thereof (by machine translation)

The preparation method of the tofacitinib intermediate V compound comprises the following steps: (1) a compound II and a compound III are subjected to a photoreaction reaction to generate an intermediate IV; (2) an intermediate IV and a methylation reagent are subjected to methylation reaction to generate a compound of formula V; wherein R is. 1 And R2 Are each independently an amino protecting group. The preparation method disclosed by the invention does not need to be subjected to isomer resolution purification in the preparation method, avoids using tetrahydroaluminum hydride, is low in synthesis cost, high in yield, simple in reaction condition and post-treatment operation and suitable for industrial production. (by machine translation)

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.

For the prevention and treatment of various autoimmune diseases of the new compound

Disclosed is an isoxazole derivative that inhibits the activity of the Janus kinases (JAKs), the structure thereof as presented in formula I, formula II, formula IX, and formula XI. The substituent groups in the formulas are described in the description. Also disclosed are the pharmaceutical composition of the compound and a related use in medicine preparation.

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

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.

PYRROLO[2,3-D]PYRIMIDINE DERIVATIVES; THEIR INTERMEDIATES AND SYNTHESIS

This invention relates to methods and intermediates useful for the synthesis of pyrrolo [2,3-d] pyrimidine compounds. Specifically novel synthetic methods and intermediates for the synthesis of 3- {(3R, 4R)-4-methyl-(7H-pyrrolo[2,3-d] pyrimidin-4-yl)-amino}-piperidin-1-yl)-3-oxo-propionitrile and its corresponding citrate salt are disclosed.