1363380-51-1

Basic information

• Product Name: 5-Chloro-3-nitropyrazolo[1,5-a]pyriMidine
• Synonyms: 5-Chloro-3-nitropyrazolo[1,5-a]pyriMidine;5-Chloro-3-nitropyrazolo[...;Pyrazolo[1,5-a]pyrimidine, 5-chloro-3-nitro-
• CAS NO: 1363380-51-1
• Molecular Formula: C₆H₃ClN₄O₂
• Molecular Weight: 198.56662
• Mol File: 1363380-51-1.mol
• Article Data: 5

Chemical Properties

• Appearance: /
• Density: 1.85±0.1 g/cm3(Predicted)
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility: Chloroform (Slightly, Heated), DMSO (Slightly)
• PKA: -3.59±0.40(Predicted)
• CAS DataBase Reference: 5-Chloro-3-nitropyrazolo[1,5-a]pyriMidine(CAS DataBase Reference)
• NIST Chemistry Reference: 5-Chloro-3-nitropyrazolo[1,5-a]pyriMidine(1363380-51-1)
• EPA Substance Registry System: 5-Chloro-3-nitropyrazolo[1,5-a]pyriMidine(1363380-51-1)

Safety Data

• Hazardous Substances Data: 1363380-51-1(Hazardous Substances Data)

Usage

Description

5-Chloro-3-nitropyrazolo[1,5-a]pyrimidine is an organic compound characterized by its unique molecular structure, which features a pyrazolo[1,5-a]pyrimidine core with a chloro substituent at the 5th position and a nitro group at the 3rd position. 5-Chloro-3-nitropyrazolo[1,5-a]pyriMidine is known for its potential applications in the pharmaceutical industry, particularly in the development of novel therapeutic agents.

Uses

Used in Pharmaceutical Industry:
5-Chloro-3-nitropyrazolo[1,5-a]pyrimidine is used as a key intermediate in the synthesis of (S)-N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide. 5-Chloro-3-nitropyrazolo[1,5-a]pyriMidine is a potent tyrosine kinase (TRK) inhibitor, which plays a crucial role in the treatment of various types of cancer.
The application of 5-Chloro-3-nitropyrazolo[1,5-a]pyrimidine in the development of TRK inhibitors is significant because these inhibitors can effectively target and inhibit the activity of TRK proteins, which are often overexpressed or mutated in cancer cells. By inhibiting TRK activity, these compounds can disrupt the signaling pathways that promote cancer cell growth and survival, thereby exhibiting potential therapeutic effects against cancer.

Upstream product

• 29274-24-6 5-chloropyrazolo[1,5-a]pyrimidine 
• 29274-22-4 4H,5H-pyrazolo[1,5-a]pyrimidine-5-one 
• 1919868-75-9 3-nitropyrazolo[1,5-a]pyrimidin-5(4H)-one 
• 1224944-43-7 sodium pyrazolo[1,5-a] pyrimidin-5-olate 

Downstream Products

• 2135871-21-3 phenyl (5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3,3a-dihydropyrazolo[1,5-a]pyrimidin-3-yl)carbamate 
• 1223404-90-7 (R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3-nitropyrazolo[1,5-a]pyrimidine 
• 1223403-58-4 (3S)-N-[5-[(2R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidi n-3-yl]-3-hydroxypyrrolidine-1-carboxamide 
• 1223405-08-0 (S)-N-(5-((R)-2-(2,5-difluorophenyl)-pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide hydrogen sulfate 
• 1223404-88-3 5-[(2R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-amine 

Relevant articles and documents

Clean process for preparing larotinib intermediate

The invention discloses a clean process for preparing a larotinib intermediate, belonging to the field of organic synthesis. Key technical points of the invention are as follows: the clean process comprises the following steps: step 1, preparing a Vilsmeier reagent from a non-phosphorus reagent and N,N-dimethylformamide in an aprotic organic solvent; step 2, adding 5-hydroxy-6-nitropyrrole[1,5-a]pyrimidine into the Vilsmeier reagent prepared in the step 1, and carrying out a chlorination reaction; step 3, after the chlorination reaction is finished, adding water into a reaction system, separating a product from the reaction system, and carrying out filtering, washing and drying; and step 4, layering a filtrate, and recovering an organic layer for reuse. According to the invention, the yield of the obtained larotinib intermediate is high; discharging of a phosphorus waste liquid can be completely eradicated for an original process; and the environment is protected.

Synthesis method of Larotrectinib intermediate and Larotrectinib

The invention discloses a synthesis method of Larotrectinib and a Larotrectinib intermediate. N-Boc pyrrolidone and 2,5-difluorophenyl magnesium bromide serve as raw materials, an intermediate A-1 isprepared, the intermediate A-1 is subjected to chiral catalysis hydrogenation, cyclization or first cyclization and afterwards chiral catalysis hydrogenation to obtain a chiral pyrrodlidine intermediate A-4, the intermediate A-4 and an intermediate B-3 are condensed to obtain an intermediate AB-1, the intermediate AB-1 is reduced to obtain an intermediate AB-2, the AB-2 is acylated to obtain an intermediate AB-3, and the AB-3 is subjected to a substitution reaction to obtain the target product Larotrectinib (AB-4). The intermediate A-4 with a high yield and high chiral purity is obtained through a chiral catalysis method, the B-3 with a high yield is obtained through a solvent-free one-pot method, and the Larotrectinib (AB-4) with a high yield and high purity is obtained. According to themethod, the reaction condition can also be applied to large-scale preparation, the method is suitable for industrial production, and therefore, the method has high practical values and social and economic benefits.

CRYSTALLINE FORM OF (S)-N-(5-((R)-2-(2,5-DIFLUOROPHENYL)-PYRROLIDIN-1-YL)-PYRAZOLO[1,5-A]PYRIMIDIN-3-YL)-3-HYDROXYPYRROLIDINE-1-CARBOXAMIDE HYDROGEN SULFATE

A novel crystalline form of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, pharmaceutical compositions containing said crystalline form and the use of said crystalline form in the treatment of pain, cancer, inflammation, neurodegenerative disease or Trypanosoma cruzi infection are disclosed. In some embodiments, the novel crystalline form comprises a stable polymorph of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide hydrogen sulfate. The present invention is further directed to a process for the preparation of the novel crystalline form.