29274-24-6

Basic information

• Product Name: 5-Chloropyrazolo[1,5-a]pyrimidine
• Synonyms: 5-CHLOROPYRAZOLO[1,5-A]PYRIMIDINE;5-Chloropyrazolo[1,5-a]py...;Pyrazolo[1,5-a]pyriMidine, 5-chloro-;5-chloro-4,5-dihydropyrazolo[1,5-a]pyrimidine
• CAS NO: 29274-24-6
• Molecular Formula: C₆H₄ClN₃
• Molecular Weight: 153.57
• Product Categories: Heterocycle-Pyrimidine series
• Mol File: 29274-24-6.mol
• Article Data: 18

Chemical Properties

• Appearance: /
• Density: 1.514 g/cm³
• Refractive Index: 1.713
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• PKA: -0.49±0.30(Predicted)
• CAS DataBase Reference: 5-Chloropyrazolo[1,5-a]pyrimidine(CAS DataBase Reference)
• NIST Chemistry Reference: 5-Chloropyrazolo[1,5-a]pyrimidine(29274-24-6)
• EPA Substance Registry System: 5-Chloropyrazolo[1,5-a]pyrimidine(29274-24-6)

Safety Data

• RIDADR: UN2811
• HazardClass: IRRITANT
• Hazardous Substances Data: 29274-24-6(Hazardous Substances Data)

Usage

Uses

5-Chloropyrazolo[1,5-a]pyrimidine was used in the preparation of β-substituted biarylphenylalanine amides as selective amino amide dipeptidyl peptidase IV inhibitors for treatment of type 2 diabetes.

InChI:InChI=1/C6H4ClN3/c7-5-2-4-10-6(9-5)1-3-8-10/h1-4H

Upstream product

• 29274-22-4 4H,5H-pyrazolo[1,5-a]pyrimidine-5-one 
• 1159981-95-9 5-bromopyrazolo[1,5-a]pyrimidine 
• 29274-22-4 pyrazolo[1,5-a]pyrimidine-5-ol 

Downstream Products

• 705262-65-3 5-iodo-pyrazolo[1,5-a]pyrimidine 
• 1228351-86-7 3-pyrazolo[1,5-a]pyrimidin-5-ylethynyl-benzonitrile 
• 1364890-59-4 (R)-5-(4,4-difluoro-2-(3-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine 
• 1621718-77-1 2,4-difluoro-N-(2-methoxy-5-(pyrazolo[1,5-a]pyrimidin-5-yl)pyridin-3-yl)benzenesulfonamide 
• 1621718-51-1 2,4-difluoro-N-(5-(3-(3-hydroxyprop-1-yn-1-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-2-methoxypyridin-3-yl)benzenesulfonamide 
• 1224288-92-9 5-chloropyrazolo[1,5-a]pyrimidine-3-carbonitrile 
• 1621718-29-3 N-(5-(3-cyanopyrazolo[1,5-a]pyrimidin-5-yl)-2-methoxypyridin-3-yl)-2,4-difluorobenzenesulfonamide 
• 1256162-94-3 5-chloropyrazolo[1,5-a]pyrimidine-3-carbaldehyde 

Relevant articles and documents

Optimization of pyrazolo[1,5-a]pyrimidines lead to the identification of a highly selective casein kinase 2 inhibitor

Casein kinase 2 (CK2) is a constitutively expressed serine/threonine kinase that has a large diversity of cellular substrates. Thus, CK2 has been associated with a plethora of regulatory functions and dysregulation of CK2 has been linked to disease development in particular to cancer. The broad implications in disease pathology makes CK2 an attractive target. To date, the most advanced CK2 inhibitor is silmitasertib, which has been investigated in clinical trials for treatment of various cancers, albeit several off-targets for silmitasertib have been described. To ascertain the role of CK2 inhibition in cancer, other disease and normal physiology the development of a selective CK2 inhibitor would be highly desirable. In this study we explored the pyrazolo [1,5-a]pyrimidine hinge-binding moiety for the development of selective CK2 inhibitors. Optimization of this scaffold, which included macrocyclization, led to IC20 (31) a compound that displayed high in vitro potency for CK2 (KD = 12 nM) and exclusive selectivity for CK2. X-ray analysis revealed a canonical type-I binding mode for IC20 (31). However, the polar carboxylic acid moiety that is shared by many CK2 inhibitors including silmitasertib was required for potency but limits the cellular activity of IC20 (31) and the cellular IC50 dropped to the low micromolar range. In summary, IC20 (31) represents a highly selective and potent inhibitor of CK2, which can be used as a tool compound to study CK2 biology and potential new applications for the treatment of diseases.

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.

COMPOUNDS AND THEIR METHODS OF USE

The present invention is directed to, in part, fused heteroaryl compounds and compositions useful for preventing and/or treating a disease or condition relating to aberrant function of a voltage-gated, sodium ion channel, for example, abnormal late/persistent sodium current. Methods of treating a disease or condition relating to aberrant function of a sodium ion channel including Dravet syndrome or epilepsy are also provided herein.