1420478-89-2

Basic information

• Product Name: (S)-benzyl 2-(8-amino-1-(4-(pyridin-2-ylcarbamoyl)phenyl)imidazo[1,5-a]pyrazin-3-yl)pyrrolidine-1-carboxylate
• Synonyms: (S)-benzyl 2-(8-amino-1-(4-(pyridin-2-ylcarbamoyl)phenyl)imidazo[1,5-a]pyrazin-3-yl)pyrrolidine-1-carboxylate;(S)-2-{8-Amino-1-[4-(pyridin-2-ylcarbamoyl)-phenyl]-imidazo[1,5-a] pyrazin-3-yl}-pyrrolidine-1-carboxylic acid benzyl ester;1-Pyrrolidinecarboxylic acid, 2-[8-amino-1-[4-[(2-pyridinylamino)carbonyl]phenyl]imidazo[1,5-a]pyrazin-3-yl]-, phenylmethyl ester, (2S)-
• CAS NO: 1420478-89-2
• Molecular Formula: C₃₀H₂₇N₇O₃
• Molecular Weight: 533.58048
• Mol File: 1420478-89-2.mol

Chemical Properties

• Appearance: /
• Density: 1.39±0.1 g/cm3(Predicted)
• PKA: 11.47±0.70(Predicted)
• CAS DataBase Reference: (S)-benzyl 2-(8-amino-1-(4-(pyridin-2-ylcarbamoyl)phenyl)imidazo[1,5-a]pyrazin-3-yl)pyrrolidine-1-carboxylate(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-benzyl 2-(8-amino-1-(4-(pyridin-2-ylcarbamoyl)phenyl)imidazo[1,5-a]pyrazin-3-yl)pyrrolidine-1-carboxylate(1420478-89-2)
• EPA Substance Registry System: (S)-benzyl 2-(8-amino-1-(4-(pyridin-2-ylcarbamoyl)phenyl)imidazo[1,5-a]pyrazin-3-yl)pyrrolidine-1-carboxylate(1420478-89-2)

Safety Data

• Hazardous Substances Data: 1420478-89-2(Hazardous Substances Data)

Usage

Uses

Used in Medicinal Chemistry:
(S)-benzyl 2-(8-amino-1-(4-(pyridin-2-ylcarbamoyl)phenyl)imidazo[1,5-a]pyrazin-3-yl)pyrrolidine-1-carboxylate is used as a potential pharmaceutical candidate for the development of new drugs due to its unique molecular structure and potential pharmacological properties.
Used in Biochemistry:
In the field of biochemistry, (S)-benzyl 2-(8-amino-1-(4-(pyridin-2-ylcarbamoyl)phenyl)imidazo[1,5-a]pyrazin-3-yl)pyrrolidine-1-carboxylate may be employed as a research tool to study the interactions between biological molecules and its potential effects on various biochemical processes.
Used in Drug Development:
(S)-benzyl 2-(8-amino-1-(4-(pyridin-2-ylcarbamoyl)phenyl)imidazo[1,5-a]pyrazin-3-yl)pyrrolidine-1-carboxylate is used as a compound in drug development to explore its potential therapeutic applications and to design new drugs with improved efficacy and safety profiles. Further studies are needed to understand its mechanism of action, pharmacokinetics, and potential side effects.

Upstream product

• 300401-95-0 4-iodo-N-(pyridin-2-yl)benzamide 
• 61350-60-5 (S)-benzyloxycarbonyl-proline acid chloride 
• 1122-91-4 4-bromo-benzaldehyde 
• 1333433-59-2 (S)-benzyl 2-carbamimidoylpyrrolidine-1-carboxylate 
• 504-29-0 2-aminopyridine 
• 180516-87-4 4-carboxyphenylboronic acid pinacol ester 
• 1148-11-4 N-Benzyloxycarbonyl-L-proline 
• 1418307-17-1 benzyl (S)-2-(((3-chloropyrazin-2-yl)methyl)carbamoyl)pyrrolidine-1-carboxylate 
• 850568-25-1 4-(pyridin-2-yl-aminocarbonyl)benzeneboronic acid 
• 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 
• 586-76-5 4-Bromobenzoic acid 
• 14547-83-2 4-bromo-N-(pyridin-2-yl)benzamide 

Downstream Products

• 1420478-90-5 4-{8-amino-3-[(2S)-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.

Preparation method capable of acalabrutinib being used for treating leukemia

The invention relates to a preparation method of acalabrutinib capable of being used for treating leukemia. The synthesis method of the compound 3 is optimized, so that according to the method, 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 catalyst nickel is prevented from being adopted, and large-scale production is facilitated; in the preparation of the compound 8, under the condition of a catalyst, large-scale preparation is realized by adding an ammonia water closed system, so that a method of introducing ammonia gas at an extremely low temperature is avoided, and large-scale production is facilitated.

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.

Acalabrutinib and its intermediate synthesis method (by machine translation)

The invention discloses a method for synthesizing Acalabrutinib, including proline derivatives of formula L - 1 and 2 - chloro - 2 - formyl acetonitrile as the starting material by direct condensation and cyclization of formula 2, after the bromo acetal with low-cost [...] methanol intermediate obtained by reaction of formula 3, followed by hydrolysis, cyclization reaction to obtain the key intermediate of formula 6, then with the borate intermediates of formula 8 to Suzuki coupling, then deprotected and get of formula 10, finally with the final product is obtained butynoic acid condensation Acalabrutinib type 11. The route the operation is simple, not only higher total yield, purity of the obtained products is also high, and suitable for production. (by machine translation)

The compounds of structure containing conjugated zincon, its pharmaceutical composition and use thereof (by machine translation)

The present invention relates to compounds having a structure containing conjugated zincon, its pharmaceutical composition and use, and in particular relates to the general formula (I) or a salt thereof to the compound represented by the, pharmaceutical compositions thereof, and its as BTK inhibitors and/or B cell activation inhibitor, for the prevention or treatment B cell activity with abnormal and/or the use of the BTK-related diseases. The compounds of lymphoma, breast cancer, liver cancer, colon cancer, gastric cancer, such as lung cancer and cervical cancer cell has better lethal effect, note has potential for the treatment of cancer and self-immune diseases related to potential. (by machine translation)

PROCESSES FOR THE PREPARATION OF ACALABRUTINIB AND INTERMEDIATES THEREOF

The present invention provides processes for the preparation of Acalabrutinib (1), as well as intermediates useful in the preparation thereof. In particular, processes are provided for coupling of a compound of Formula (5) and 2-butynoic acid in the presence of Carbodiimide (8) to afford Acalabrutinib (1).

BTK INHIBITORS TO TREAT SOLID TUMORS THROUGH MODULATION OF THE TUMOR MICROENVIRONMENT

In certain embodiments, the invention includes therapeutic methods of using a BTK inhibitor to treat solid tumor cancers by modulation of the tumor microenvironment, including macrophages, monocytes, mast cells, helper T cells, cytotoxic T cells, regulatory T cells, natural killer cells, myeloid-derived suppressor cells, regulatory B cells, neutrophils, dendritic cells, and fibroblasts.

THERAPEUTIC COMBINATIONS OF A BTK INHIBITOR, A PI3K INHIBITOR, A JAK-2 INHIBITOR, AND/OR A BCL-2 INHIBITOR

Therapeutic combinations of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the γ- and δ-isoforms and selective for both γ- and δ-isoforms (PI3K-γ,δ, PI3K-γ, and PI3K-δ), a Janus kinase-2 (JAK-2) inhibitor, a Bruton's tyrosine kinase (BTK) inhibitor, and/or a B-cell lymphoma-2 (BCL-2) inhibitor are described. In some embodiments, the invention provides therapeutic combinations of a PI3K-δ inhibitor and a BTK inhibitor, a JAK-2 and a BTK inhibitor, and a BCL-2 and BTK inhibitor.

THERAPEUTIC COMBINATIONS OF A BTK INHIBITOR, A PI3K INHIBITOR, A JAK-2 INHIBITOR AND/OR A CDK 4/6 INHIBITOR

Therapeutic combinations of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the γ- and δ-isoforms and selective for both γ- and δ-isoforms (PI3K-γ,δ, PI3K-γ, and PI3K-δ, a Janus kinase-2 (JAK-2) inhibitor, a cyclin-dependent kinase- 4/6 (CDK4/6) inhibitor, and/or a Bruton's tyrosine kinase (BTK) inhibitor are described. In certain embodiments, the invention includes therapeutic combinations of a cyclin-dependent kinase-4/6 (CDK4/6) inhibitor and a BTK inhibitor, a PI3K-δ inhibitor and a BTK inhibitor, a JAK-2 and a BTK inhibitor, and a JAK-2, PI3K-δ, and BTK inhibitor.