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

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

Used in Pharmaceutical Industry:
5-Chloropyrazolo[1,5-a]pyrimidine is used as a key intermediate in the synthesis of various biologically active compounds. Its unique structure allows it to be a valuable building block for the development of new drugs with specific therapeutic applications.
Used in the Treatment of Type 2 Diabetes:
5-Chloropyrazolo[1,5-a]pyrimidine is used as a starting material for the preparation of β-substituted biarylphenylalanine amides. These amides are selective amino amide dipeptidyl peptidase IV (DPP-IV) inhibitors, which play a crucial role in the treatment of type 2 diabetes. By inhibiting DPP-IV, these compounds help regulate blood glucose levels, providing an effective treatment option for patients with 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 pyrazolo[1,5-a]pyrimidine-5-ol 
• 29274-22-4 4H,5H-pyrazolo[1,5-a]pyrimidine-5-one 
• 1159981-95-9 5-bromopyrazolo[1,5-a]pyrimidine 

Downstream Products

• 960613-96-1 3-bromo-5-chloro-pyrazolo[1,5-a]pyrimidine 
• 705262-65-3 5-iodo-pyrazolo[1,5-a]pyrimidine 
• 923595-58-8 5-chloro-3-iodopyrazolo[1,5-a]pyrimidine 
• 1223404-89-4 (R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine 
• 1228351-86-7 3-pyrazolo[1,5-a]pyrimidin-5-ylethynyl-benzonitrile 
• 1269646-71-0 (S)-4-(5-(4-isopropyl-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)benzoic acid 
• 1269646-72-1 (S)-4-(5-(4-isopropyl-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)benzohydrazide 
• 1269643-51-7 (S)-3-(3-(4-(5-amino-1,3,4-oxadiazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-one 
• 1269646-73-2 (S)-2-(4-(5-(4-isopropyl-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)benzoyl)hydrazinecarbothioamide 
• 1269643-53-9 (S)-3-(3-(4-(5-amino-1,3,4-thiadiazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-one 
• 1269646-74-3 (S)-N'-(1-iminoethyl)-4-(5-(4-isopropyl-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)benzohydrazide 
• 1269643-55-1 (S)-4-isopropyl-3-(3-(4-(5-methyl-4H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)oxazolidin-2-one 
• 1269646-75-4 (S)-5-(4-(5-(4-isopropyl-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)phenyl)-1,3,4-oxadiazol-2(3H)-one 
• 1269646-76-5 (S)-N-(2-hydroxyethyl)-2-(4-(5-(4-isopropyl-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)benzoyl)hydrazinecarboxamide 

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.

Method for efficiently synthesizing 5-chloropyrazolo[1,5-a]pyrimidine

The invention discloses a method for efficiently synthesizing 5-chloropyrazolo[1,5-a]pyrimidine. The synthesis route comprises: carrying out a reaction on a compound A and a compound B to obtain a compound C, and carrying out a reaction on the compound C and phosphorus oxychloride to obtain a compound D, ie., 5-chloropyrazolo[1,5-a]pyrimidine, wherein the reaction formulas A, B, C and D are defined in the specification. According to the present invention, the method has characteristics of mild synthesis condition, low influence of post-treatment on environment, simple process, inexpensive andeasily-available raw material, simple operation and wide industrial application prospect and market value, and is suitable for industrial large-scale production.

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.

Heterocyclic Compound

The present invention provide a compound having an orexin receptor antagonistic activity, which is expected to be useful as medicaments such as agents for the prophylaxis or treatment of sleep disorder, depression, anxiety disorder, panic disorder, schizophrenia, drug dependence, Alzheimer's disease and the like. The present invention relates to a compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof.

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.

Pyrazolo [1, 5 - a] pyrimidine compounds and their preparation method and medical use

The invention relates to a pyrazolo[1,5-a]miazine compound and its preparation method and medical use. The invention relates to the preparation method of the pyrazolo[1,5-a]miazine compound shown in the general formula (I) and its salt, a pharmaceutical c

FUSED RING HETEROARYL COMPOUNDS AND THEIR USE AS TRK INHIBITORS

The disclosure provides novel chemical compounds represented by Formula I or a pharmaceutically acceptable salt, solvate, polymorph, ester, tautomer or prodrug thereof. The compounds can be used as an inhibitor of Trk and are useful in the treatment of pain, cancer, inflammation, neurodegenerative disease and certain infectious diseases. In some compounds of Formula I, Q is —CH═CR3C(O)NR4R5, —C≡CC(O)NR4R5, or

Combination of mTOR inhibitors and P13-kinase inhibitors, and uses thereof

The present invention provides for a method for treating a disease condition associated with PI3-kinase α and/or mTOR in a subject. In another aspect, the invention provides for a method for treating a disease condition associated with PI3-kinase α and/or mTOR in a subject. In yet another aspect, a method of inhibiting phosphorylation of both Akt (S473) and Akt (T308) in a cell is set forth.

COMBINATION OF KINASE INHIBITORS AND USES THEREOF

The present invention provides for a method for treating a disease condition associated with PI3-kinase a and/or a receptor tyrosine kinase (RTK) in a subject. In another aspect, the invention provides for a method for treating a disease condition associated with PI3-kinase α and/or an RTK in a subject. In yet another aspect, a method of inhibiting phosphorylation of Akt (S473) in a cell is set forth.

COMBINATION OF KINASE INHIBITORS AND USES THEREOF

The present invention provides for a method for treating a disease condition associated with PI3-kinase a and/or mTOR in a subject. In another aspect, the invention provides for a method for treating a disease condition associated with PI3-kinase a and/or mTOR in a subject. In yet another aspect, a method of inhibiting phosphorylation of both Akt (S473) and Akt (T308) in a cell is set forth. The present invention also provides a pharmaceutical kit effective for treating a disease condition associated with PI3 -kinase α and/or mTOR in a subject.