1420478-90-5

Basic information

• Product Name: Acalabrutinib Intermediate
• Synonyms: Acalabrutinib Intermediate;acarabrutinib intermediate;(S)-4-(8-Amino-3-pyrrolidin-2-yl-imidazo[1,5-a]pyrazin-1-yl)-N- pyridin-2-yl-benzamide;Benzamide, 4-[8-amino-3-(2S)-2-pyrrolidinylimidazo[1,5-a]pyrazin-1-yl]-N-2-pyridinyl-;4-[8-amino-3-(2S)-2-pyrrolidinylimidazo[1,5-a]pyrazin-1-yl]-N-2-pyridinyl-Benzamide
• CAS NO: 1420478-90-5
• Molecular Formula: C₂₂H₂₁N₇O
• Molecular Weight: 399.45
• Product Categories: Intermediates
• Mol File: 1420478-90-5.mol
• Article Data: 10

Chemical Properties

• Appearance: /
• Density: 1.46±0.1 g/cm3(Predicted)
• PKA: 11.47±0.70(Predicted)
• CAS DataBase Reference: Acalabrutinib Intermediate(CAS DataBase Reference)
• NIST Chemistry Reference: Acalabrutinib Intermediate(1420478-90-5)
• EPA Substance Registry System: Acalabrutinib Intermediate(1420478-90-5)

Safety Data

• Hazardous Substances Data: 1420478-90-5(Hazardous Substances Data)

Usage

General Description

Acalabrutinib Intermediate, also known as 4-(3-(4-amino-3-(3-ethoxy-7-(3-(4-phenoxyphenyl)propoxy)quinolin-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)-N-methylbenzamide, is a chemical compound used in the synthesis of the drug acalabrutinib, which is a selective inhibitor of Bruton's tyrosine kinase (BTK) and is used in the treatment of certain types of cancers. This intermediate is a key building block in the manufacturing process of acalabrutinib and is essential for the production of the drug. It plays a critical role in the formation of the molecular structure of acalabrutinib, allowing for the compound to exhibit its specific pharmacological properties and therapeutic effects.

Upstream product

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• 14547-83-2 4-bromo-N-(pyridin-2-yl)benzamide 
• 1148-11-4 N-Benzyloxycarbonyl-L-proline 
• 1418307-17-1 benzyl (S)-2-(((3-chloropyrazin-2-yl)methyl)carbamoyl)pyrrolidine-1-carboxylate 
• 1420478-89-2 (S)-2-((1-(4-(pyridin-2-ylcarbamoyl)phenyl)-8-amino)imidazole[1,5-a]pyrazin-2-yl)pyrrolidine1-yl-carboxylic acid benzyl ester 
• 1420478-88-1 benzyl (2S)-2-(8-amino-1-bromo-imidazo[1,5-a]pyrazin-3-yl)pyrrolidine-1-carboxylate 
• 1420478-87-0 benzyl (2S)-2-(1-bromo-8-chloro-imidazo[1,5-a]pyrazin-3-yl)pyrrolidine-1-carboxylate 
• 1418307-18-2 (S)-2-(8-chloroimidazo[1,5-a]pyrazin-3-yl)-1-pyrrolidinecarboxylic acid benzyl ester 

Downstream Products

• 1420477-56-0 (S,E)-4-(8-amino-3-(1-(4-(pyrrolidin-1-yl)but-2-enoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide 
• 1420477-60-6 4-{8-amino-3-[(2S)-1-(1-oxo-2-butyn-1-yl)pyrrolidin-2-yl]imidazo[1,5-a]pyrazin-1-yl}-N-(pyridin-2-yl)benzamide 

Relevant articles and documents

Method for preparing Acalabrutinib, in particular to method for preparing Acalabrutinib

The invention relates to the field of chemical synthesis, in particular to a chemical synthesis method for preparing Acalabrutinib. The synthesis method of the compound 3 is optimized, wherein the cyano compound 2 is reduced to obtain the compound 3 by adopting a method of generating borane in situ under the conditions of indium trichloride and sodium borohydride. The method is simple and convenient to operate, a special reaction container and hydrogen are not needed for reduction, a high-risk material catalyst nickel is prevented from being adopted, and large-scale production is facilitated.In the preparation of the compound 15, water is used as a solvent, equivalent hydrogen peroxide is added to react the compound 13 with the compound 14 to prepare the compound 15, so that the method iseconomic and environment-friendly, the post-treatment is simple and convenient, and the reaction liquid is directly subjected to centrifugal operation; in addition, the yield is high and can reach 90% or above; and the compound 15 is high in purity and does not need to be further purified, so that the technology can satisfy the requirements of industrial production.

PROCESS FOR THE PREPARATION OF ACALABRUTINIB AND ITS INTERMEDIATES

The present invention provides an improved and industrially viable process for the preparation of Acalabrutinib and its intermediates in high yield and eliminating the use of time-consuming purification process. The present invention also relates to the purification of (S)-4-(8-Amino-3-(pyrrolidin-2-yl)imidazo[1,5-alpyrazin-1-yl)-N-(pyridin-2-yl) benzamide, a key intermediate for the preparation of Acalabrutinib. Further present invention relates to new polymorphic form of Acalabrutinib.

PROCESSES TO PRODUCE ACALABRUTINIB

The present invention relates to a method for preparing the compound of formula IV, compound of formula XI, and acalabrutinib, a new generation of bruton tyrosine kinase (BTK) inhibitor.