1557267-42-1

Basic information

• Product Name: N-(3-{2-[3-Fluoro-4-(4-methyl-piperazin-1-yl)-phenylamino]-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy}-phenyl)-acrylamide
• Synonyms: N-(3-{2-[3-Fluoro-4-(4-methyl-piperazin-1-yl)-phenylamino]-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy}-phenyl)-acrylamide;Avi Tini;Avitinib;2-Propenamide, N-[3-[[2-[[3-fluoro-4-(4-methyl-1-piperazinyl)phenyl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]phenyl]-;Avitinib(AC0010/AC0010MA);Avitinib free base;Avitinib (AC0010)
• CAS NO: 1557267-42-1
• Molecular Formula: C₂₆H₂₆FN₇O₂
• Molecular Weight: 487.5287432
• EINECS: 1592732-453-0
• Mol File: 1557267-42-1.mol
• Article Data: 7

Chemical Properties

• Appearance: /
• Density: 1.365±0.06 g/cm3(Predicted)
• PKA: 12.48±0.50(Predicted)
• CAS DataBase Reference: N-(3-{2-[3-Fluoro-4-(4-methyl-piperazin-1-yl)-phenylamino]-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy}-phenyl)-acrylamide(CAS DataBase Reference)
• NIST Chemistry Reference: N-(3-{2-[3-Fluoro-4-(4-methyl-piperazin-1-yl)-phenylamino]-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy}-phenyl)-acrylamide(1557267-42-1)
• EPA Substance Registry System: N-(3-{2-[3-Fluoro-4-(4-methyl-piperazin-1-yl)-phenylamino]-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy}-phenyl)-acrylamide(1557267-42-1)

Safety Data

• Hazardous Substances Data: 1557267-42-1(Hazardous Substances Data)

Usage

Description

Avitinib is a pyrrolopyrimidine-based, irreversible inhibitor of the epidermal growth factor receptor (EGFR). It is selective for EGFR-active and T790M mutations, exhibiting a 298-fold increase in potency compared with wild-type EGFR. In a xenograft model, oral administration of 500 mg/kg avitinib was shown to result in complete remission of tumors with EGFR-active and T790M mutations.

Upstream product

• 814-68-6 acryloyl chloride 
• 90213-66-4 2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine 
• 1557268-80-0 pivalic acid (2-chloro-4-(3-nitrophenoxy)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl ester 
• 109-01-3 1-methyl-piperazine 
• 369-34-6 3,4-difluoronitrobenzene 
• 221198-29-4 3-fluoro-4-(4-methylpiperazin-1-yl)nitrobenzene 
• 13040-21-6 N-(3-hydroxyphenyl)prop-2-enamide 
• 442847-52-1 2,4-dichloro-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3 -d]pyrimidine 
• 1557268-35-5 2-chloro-4-(3-nitrophenoxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-D]pyrimidine 
• 1557268-58-2 N-(3-fluoro-4- (4-methylpiperazin-1-yl)phenyl)-4-(3-nitrophenoxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-D]pyrimidin-2-amine 
• 1557268-61-7 4-(3-aminophenoxy)-N-(3-fluoro-4-(4-methylpiperazin-1-yl)phenyl)-7-((2-(trimethylsilyl)ethyloxy)methyl)-7H-pyrrolo[2,3-D]pyrimidin-2-amine 
• 1557268-64-0 N-(3-(2-(3-fluoro-4-(4-methylpiperazin-1-yl)phenylamino)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)phenyl)acrylamide 
• 1557267-50-1 N-(3-(2-(3-fluoro-4-(4-methylpiperazin-1-yl)phenylamino)-7-(hydroxymethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)phenyl)acrylamide 
• 221198-99-8 1-(2-fluoro-4-aminophenyl)-4-methylpiperazine 

Downstream Products

• 1557268-88-8 N-(3-(2-(3-fluoro-4-(4-methylpiperazin-1-yl)phenylamino)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)phenyl)acrylamide maleate 
• 1557268-88-8 N-(3-(2-(3-fluoro-4-(4-methylpiperazin-1-yl)phenylamino)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)phenyl)acrylamide maleate 
• 1557268-88-8 N-(3-(2-(3-fluoro-4-(4-methylpiperazin-1-yl)phenylamino)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)phenyl)acrylamide fumarate 
• 1557268-88-8 C₄H₄O₄*C₂₆H₂₆FN₇O₂ 

Relevant articles and documents

The synthesis and bioactivity of pyrrolo[2,3-d]pyrimidine derivatives as tyrosine kinase inhibitors for NSCLC cells with EGFR mutations

EGFR mutations are an ongoing challenge in the treatment of NSCLC, and demand continuous updating of EGFR TKI drug candidates. Pyrrolopyrimidines are one group of versatile scaffolds suitable for tailored drug development. However not many precedents of this type of pharmacophore have been investigated in the realm of third generation of covalent EGFR-TKIs. Herein, a series of pyrrolo[2,3-d]pyrimidine derivatives able to block mutant EGFR activity in a covalent manner were synthesized, through optimized Buchwald-Hartwig C–N cross coupling reactions. Their preliminary bioactivity and corresponding inhibitory mechanistic pathways were investigated at molecular and cellular levels. Several compounds exhibited increased biological activity and enhanced selectivity compared to the control compound. Notably, compound 12i selectively inhibits HCC827 cells harboring the EGFR activating mutation with up to 493-fold increased efficacy compared to in normal HBE cells. Augmented selectivity was also confirmed by kinase enzymatic assay, with the test compound selectively inhibiting the T790 M activating mutant EGFRs (IC50 values of 0.21 nM) with up to 104-fold potency compared to the wild-type EGFR (IC50 values of 22 nM). Theoretical simulations provide structural evidence of selective kinase inhibitory activity. Thus, this series of pyrrolo[2,3-d]pyrimidine derivatives could serve as a starting point for the development of new EGFR-TKIs.

Preparing method of Avitinib

The invention discloses a preparing method of Avitinib. The method includes the following steps of A, dissolving 2,4-dichloropyrimidine, XPhos, Pd2(dba)3 and 3-floro-4-(4-methyl piperazine-1-yl)aniline in a propyl alcohol solvent for reaction to obtain an intermediate I; B, dissolving tBu-protected 3-nitrophenol in an ethyl alcohol solvent, and adding iron powder and ammonium chloride to obtain tBu-protected 3-amino-phenol; C, dissolving the tBu-protected 3-amino-phenol and diisopropylethylamine in dichloromethane, and dropwise adding isopentyl chloride for reaction to obtain an intermediate II; D, making the intermediate II flow backwards in a rifluoroacetic acid solvent, and removing tBu protection to obtain an intermediate III; E, mixing the intermediate I, the intermediate III and dimethylformamide for reaction to obtain the end product. The method is simple in operation and high in yield.

PHARMACEUTICAL SALTS, PHYSICAL FORMS, AND COMPOSITIONS OF PYRROLOPYRIMIDINE KINASE INHIBITORS, AND METHODS OF MAKING SAME

The present invention relates to methods of making certain pyrrolopyrimidine derivatives, which are useful in the treatment of proliferation disorders and other diseases related to the dysregulation of kinase (such as, but not limited to, EGFR (including HER), Alk, PDGFR, BLK, BMX/ETK, BTK, FLT3(D835Y), ITK, JAK1, JAK2, JAK3, TEC and TXK) and/or the respective pathways, salts, polymorphs, and amorphous forms of said compounds, synthetic intermediates for preparing said compounds, and pharmaceutical compositions comprising said compounds and methods for making such compositions.