220127-57-1

Basic information

• Product Name: Imatinib mesylate
• Synonyms: 4-[(4-methyl-1-piperazinyl)methyl]-n-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]-benzamide monomethanesulfonate;STI-571;IMATINIB BASE(IMA-3);ImatinibMesylate/Gleevec;Imatinib Methanesulfonate, STI-571, CGP-57148B, Glivec,;IMATINIB MESYLATE (IMATINIB METHANESULFONATE);alpha-IMATINIB MESYLATE;Imatinib mesylate(TINIBS )
• CAS NO: 220127-57-1
• Molecular Formula: C30H35N7O4S
• Molecular Weight: 589.71
• EINECS: 1308068-626-2
• Product Categories: Active Pharmaceutical Ingredients;Intermediates & Fine Chemicals;Pharmaceuticals;Tyrosine Kinase Inhibitors;Aromatics;Heterocycles;API;Glivec, CGP-57148B, STI-571;Antineoplastic;Anti-cancer&immunity;Inhibitors;Anticancer
• Mol File: 220127-57-1.mol

Chemical Properties

• Melting Point: 214-224°C
• Boiling Point: 754.9 °C at 760 mmHg
• Flash Point: 410.3 °C
• Appearance: white to beige/
• Density: 0.858g/mLat 25°C(lit.)
• Storage Temp.: -20°C Freezer
• Solubility: H2O: soluble10mg/mL, clear
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO or water may be stored at -20°C for up to 3 months.
• CAS DataBase Reference: Imatinib mesylate(CAS DataBase Reference)
• NIST Chemistry Reference: Imatinib mesylate(220127-57-1)
• EPA Substance Registry System: Imatinib mesylate(220127-57-1)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• WGK Germany: 3
• RTECS: CV5520550
• Hazardous Substances Data: 220127-57-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Imatinib mesylate is used as an anticancer agent for the treatment of chronic myelogenous leukemia (CML) and gastrointestinal stromal tumors (GIST) that express Kit. It is effective in blast crisis, accelerated phase, or chronic phase after interferon-alpha failure. Imatinib has advantages over IFN-alpha, such as reduced toxicity, more rapid hematological response, higher rate of cytogenic response, and oral administration.
Used in Antifungal Applications:
Imatinib mesylate is used as an echinocandin antifungal, active against infections with Aspergillus and Candida. It inhibits cell wall synthesis, providing an alternative treatment option for patients with fungal infections.
Used in Research and Development:
Imatinib mesylate is used as a multi-target inhibitor of v-Abl, c-Kit, and PDGFR in research and development for the study of various oncogenic events and the development of targeted therapies for cancer treatment.
Used in Drug Metabolism Studies:
Imatinib mesylate is used in studies related to drug metabolism, as it is primarily metabolized by the CYP3A4 enzyme system. Understanding the interaction between Imatinib and the CYP3A4 system can help in predicting potential drug-drug interactions and modifying the patient's exposure to the drug.

a small-molecule inhibitor

Imatinib mesylate (also called Gleevec) is a small-molecule inhibitor of the fusion protein Bcr-Abl, the causal agent in chronic myelogenous leukemia. As an inhibitor of PDGFR, imatinib mesylate appears to have utility in the treatment of a variety of dermatological diseases. Imatinib has been reported to be an effective treatment for FIP1L1-PDGFRalpha+ mast cell disease, hypereosinophilic syndrome, and dermatofibrosarcoma protuberans.

Originator

Novartis (Switzerland)

Biochem/physiol Actions

Imatinib mesylate is a tyrosine kinase inhibitor with antineoplastic activity. Imatinib is a potent inhibitor of the Bcr-Abl kinase encoded by the bcr-abl oncogene as well as receptor tyrosine kinases encoded by c-kit and platelet-derived growth factor receptor (PDGFR) oncogenes. Imatinib mesylate inhibition of Bcr-Abl tyrosine kinase created by the Philadelphia chromosome abnormality found in CML decreases proliferation and enhances apoptosis in leukemias CML and ALL. Inhibition of c-kit tyrosine activity inhibits mast-cell and cellular proliferation in those diseases overexpressing c-kit such as gastrointestinal stromal tumor (GIST).

References

1) Buchdunger, et al.(1996) Inhibition of the Abl Protein-Tyrosine Kinase in Vitro and in Vivo by a 2-Phenylpyrimidine Derivative; Cancer Res. 56 100 2) Heinrich et al (2000) Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor. Blood 96 925 3) Morioka et al. (2016) Effect of Collagen Type 1 or Human Fibronectin on Imatinib Cytotoxicity in Oral Squamous Cell Carcinoma; Pharmacology and Pharmacy, 7 255 [Focus Biomolecules Citation] 4) Hazekawa et al. (2017) Assessment of cytotoxicity of imatinib for oral squamous cell carcinoma by a real-time cell analysis system; E. J. Bio., 13 56 [ Focus Biomolecules Citation]

InChI:InChI=1/C29H31N7O.CH4O3S/c1-21-5-10-25(18-27(21)34-29-31-13-11-26(33-29)24-4-3-12-30-19-24)32-28(37)23-8-6-22(7-9-23)20-36-16-14-35(2)15-17-36;1-5(2,3)4/h3-13,18-19H,14-17,20H2,1-2H3,(H,32,37)(H,31,33,34);1H3,(H,2,3,4)

Upstream product

• 75-75-2 methanesulfonic acid 
• 152459-95-5 imatinib 
• 839677-18-8 4-((4-methylpiperazin-1-yl)methyl)benzamide 
• 152460-09-8 N-(5-nitro-2-methylphenyl)-4-(3-pyridinyl)-2-pyrimidineamine 
• 152460-07-6 1-(2-methyl-5-nitrophenyl)guanidine 
• 350-03-8 methyl-3-pyridylketone 
• 55314-16-4 3-(N,N-dimethylamino)-1-(pyridin-3-yl)prop-2-en-1-one 
• 99-55-8 2-methyl-5-nitroaniline 
• 152460-08-7 (2-methyl-5-nitrophenyl)guanidine nitrate 
• 152460-10-1 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine 
• 404844-11-7 4-(chloromethyl)-N-(4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]-amino}phenyl)benzamide 
• 1642-81-5 p-(chloromethyl)benzoic acid 
• 148077-69-4 4-(4-Methylpiperazin-1-ylmethyl)benzoyl chloride 
• 152460-08-7 1-(2-methyl-5-nitrophenyl)guanidine nitrate 

Relevant articles and documents

A PROCESS FOR PREPARATION OF IMATINIB BY USING VILSMEIER REAGENT

The present invention relates to a process of preparation of Imatinib, wherein said process comprises one or more steps of converting benzoic acid intermediate (formula 8) into Imatinib in presence of Vilsmeier reagent preferably under basic condition. Vilsmeier reagent in the present invention is prepared by reaction of chlorinating agent and catalyst. In a preferred embodiment Chlorinating agent is thionyl chloride and catalyst is dimethyl formamide.

Synthesis method of imatinib and imatinib mesylate

The invention relates to a synthesis method of imatinib and imatinib mesylate. The method comprises the following steps: condensing 3-acetylpyridine and N,N-dimethylformamide dimethyl acetal which aretaken as initial raw materials to obtain 3-dimethylamino-1-(3-pyridyl)-2-propen-1-one, then reacting with 2-methyl-5-nitrophenylguanidine nitrate to form a pyrimidine ring, performing nitro reductionto obtain N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidinamine, amidating the N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidinamine and 4-(chloromethyl)benzoyl chloride, performing affinitysubstitution with 1-methylpiperazine to obtain imatinib, and salifying the imatinib and methanesulfonic acid. The products obtained by the method have the advantages of few impurities, simplicity in post-treatment, high total yield, greenness, environmental protection and safety, and is suitable for a production process for large-scale industrial production of imatinib mesylate.

Preparation method of imatinib mesylate

The invention discloses a preparation method of imatinib mesylate. The method comprises the following steps: chlorinating imatinib acid[4-(4-methylpiperazine-1-ylmethyl)benzoic acid dihydrochloride] with thionyl chloride to generate an imatinib mesylate intermediate I; condensing the imatinib mesylate intermediate I with imatinib amine [N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidinamine] toobtain an imatinib mesylate intermediate II, and finally salifying the imatinib mesylate intermediate II with methanesulfonic acid to obtain imatinib mesylate. According to the invention, the raw materials imatinib acid and imatinib amine used in the method are common medical intermediates, other raw materials and reagents used in the process are convenient and easy to obtain, the reaction process and post-treatment operation are simple and convenient, the yield is high, and the production cost is effectively reduced through process optimization.

IMATINIB mesylate α crystal preparation method

The invention relates to the field of drug synthesis and discloses a preparation method of an imatinib mesylate alpha crystal form. In the preparation method, imatinib alkali is mixed with chloroform, and the mixture reacts with the methanesulfonic acid-c

An imatinib mesylate crystal form suitable for officinal uses and a preparing method thereof

The invention relates to 4-[(4-methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-phenyl]phenylamine mesylate shown as a formula (1), namely an imatinib mesylate non-needle alpha crystal form, and a preparing method thereof.

Preparation method of imatinib mesylate

The invention discloses a preparation method of imatinib mesylate. The method specifically comprises steps as follows: 4-[(4-methylpiperazin-1-yl)methyl]benzoic acid dihydrochloride type compounds II are taken as a starting material, sodium carbonate and N, N'-carbonyl diimidazole are added, acyl imidazole with higher activity is obtained, separation is not required, N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidineamine type compounds IV and a catalyst imidazole hydrochloride are directly added, the mixture reacts, free alkali imatinib is obtained, methylsulfonic acid is added for salt formation, and imatinib mesylate in an alpha crystal form is obtained after recrystallization. The preparation method has the advantages of being mild in reaction condition, lower in cost, simple and convenient to operate, high in yield, good in reaction reproducibility, economical, environment-friendly and suitable for industrial production and producing fewer side reactions.

Purification method of imatinib

The invention relates to a purification method of imatinib. The method has the characteristics of simple technique, high safety, environment friendliness, low cost and favorable repeatability, and can implement industrialized large-scale production. By using the method, the content of the genotoxic impurity N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-aminopyrimidine in the imatinib can be lowered to 2ppm or below according to the pharmacopoeia requirement, and the product purity is up to 99.8% or above.

Preparation method of non-acicular alpha crystal form imatinib mesylate

The invention discloses a preparation method of non-acicular alpha crystal form imatinib mesylate. The method comprises the following steps: (1) performing reduction reaction by taking N-(2-methyl-5-nitrophenyl)-4-(3-pyridyl)-2-aminopyrimidine as a raw material, methanol as a solvent, KBH4 as a reducing agent and ZrCl4 as a catalyst to obtain N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidineamine; (2) after activating 4-[(4-methylpiperazin-1-yl)methyl]benzoic acid dihydrochloride hemihydrates by using CBMIT, performing acylation reaction with equimolar N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidineamine by taking DMF as a solvent to obtain imatinib alkali; and (3) suspending the imatinib alkali in isopropanol, adding an acetone solution of methylsulfonic acid, heating for reflux reaction, cooling for crystallization, filtering, and drying to obtain a non-acicular imatinib mesylate alpha crystal form. The preparation method disclosed by the invention has the advantages of being simple in operation, small in environmental harm, safe, reliable, relatively short in reaction time, good in product quality, high in yield and the like, and is suitable for industrial production.

Methanesulfonic acid iraq Ma Ti nepalese crystalline α and its preparation of pharmaceutical compositions

The invention belongs to the technical field of medicine, relates to preparation of an imatinib mesylate alpha crystal and a pharmaceutical composition thereof, and provides a preparation method of the imatinib mesylate alpha crystal. The method provided by the invention is short in reaction step, simple to operate, small in toxicity of a used solvent, small in environmental pollution, high in total yield, and low in cost. The prepared product is high in purity and applicable to large-scale industrial operation. The crystalline of the prepared imatinib mesylate alpha crystal is over 60%. The pharmaceutical composition containing the imatinib mesylate alpha crystal provided by the invention has the advantages that the defects of poor liquidity, unstable thermodynamics and strong hygroscopicity of the imatinib mesylate alpha crystal are overcome, and the prepared composition is even in content and strong in stability after long-term placement.

PROCESS FOR PREPARING IMATINIB AND IMATINIB MESYLATE NON-NEEDLE SHAPED α2 FORM

The present invention relates to an efficient process and industrially feasible for the preparation of imatinib and imatinib mesylate non-needle shaped α2 form with high purity, without requiring purification by recrystallization or column chromatography. The process of the present invention is easy, fast and economical, wherein the imatinib mesylate is obtained with high yield and purity.