Imatinib

Base Information

• Chemical Name: Imatinib
• CAS No.: 152459-95-5
• Molecular Formula: C29H31N7O
• Molecular Weight: 493.611
• Hs Code.: 29339900
• European Community (EC) Number: 604-855-6
• NSC Number: 759854,743414
• UNII: BKJ8M8G5HI
• DSSTox Substance ID: DTXSID3037125
• Nikkaji Number: J1.337.143A
• Wikipedia: Imatinib
• Wikidata: Q177094
• NCI Thesaurus Code: C62035
• RXCUI: 282388
• Pharos Ligand ID: VLU17BQBSGWU
• Metabolomics Workbench ID: 42946
• ChEMBL ID: CHEMBL941
• Mol file: 152459-95-5.mol

Synonyms:alpha-(4-Methyl-1-piperazinyl)-3'-((4-(3-pyridyl)-2-pyrimidinyl amino)-p-tolu-p-toluidide;4-[(4-Methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]benzamide;

Chemical Property of Imatinib

Chemical Property:

• Appearance/Colour: off white powder
• Vapor Pressure: 6.03E-24mmHg at 25°C
• Melting Point: 113°C
• Boiling Point: 451°C
• PKA: pKa1 8.07; pKa2 3.73; pKa3 2.56; pKa4 1.52(at 25℃)
• Flash Point: 196°C
• PSA: 86.28000
• Density: 1.256 g/cm³
• LogP: 4.61210
• Storage Temp.: Refrigerator
• Solubility.: DMSO (Slightly, Heated), Methanol (Slightly, Heated)
• XLogP3: 3.5
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 7
• Exact Mass: 493.25900864
• Heavy Atom Count: 37
• Complexity: 706

Purity/Quality:

99%min ^*data from raw suppliers

Imatinib, Free base ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T,N
• Hazard Codes: T,N
• Safety Statements: 24/25

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: CC1=C(C=C(C=C1)NC(=O)C2=CC=C(C=C2)CN3CCN(CC3)C)NC4=NC=CC(=N4)C5=CN=CC=C5
• Recent ClinicalTrials: Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) PRIME Trial
• Recent EU Clinical Trials: A multicentre, randomized trial in adults with de novo Philadelphia-Chromosome positive acute lymphoblastic leukemia to assess the efficacy of ponatinib versus imatinib in combination with low-intensity chemotherapy, to compare end of therapy with indication for SCT versus TKI, blinatumomab and chemotherapy in optimal responders and to evaluate blinatumomab in suboptimal responders (GMALL-EVOLVE)
• Recent NIPH Clinical Trials: A phase 1 study of pimitespib and imatinib in patients with GIST
• General Description: Imatinib is a tyrosine kinase inhibitor clinically used to treat chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GISTs). Recent synthetic advancements have focused on improving its production by developing cost-effective, environmentally friendly methods that avoid toxic reagents and genotoxic impurities. Key innovations include the use of copper or nano-ZnO catalysts for efficient intermediate formation and selective C–N coupling reactions, yielding high-purity Imatinib with industrial applicability.

Technology Process of Imatinib

There total 96 articles about Imatinib which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 99.26%

4-((4-methylpiperazin-1-yl)methyl)benzoyl chloride dihydrochloride + N-(5-amino-2-methylphenyl)-4-(3-piridinyl)-2-pyrimidine amine → imatinib (152459-95-5)

Guidance literature:

With sodium hydroxide; In water; at 0 - 55 ℃; pH=9 - 9.5;

Reference yield: 97.52%

1-methyl-piperazine (109-01-3) + 4-(chloromethyl)-N-(4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]-amino}phenyl)benzamide (404844-11-7) → imatinib (152459-95-5)

Guidance literature:

With potassium carbonate; In N,N-dimethyl-formamide; at 80 ℃; for 4.5h; Temperature;

Reference yield: 95.8%

4-[(4-methylpiperazin-1-yl)methyl]bromobenzene (368879-17-8) + carbon monoxide (201230-82-2) + 6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1) → imatinib (152459-95-5)

Guidance literature:

With palladium diacetate; triethylamine; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; In 1,4-dioxane; at 50 ℃; for 36h; under 760.051 Torr; Reagent/catalyst; Solvent; Temperature; Inert atmosphere;

upstream raw materials:

6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine

4-(4-Methylpiperazin-1-ylmethyl)benzoyl chloride

1-methyl-piperazine

4-(chloromethyl)-N-(4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]-amino}phenyl)benzamide

Downstream raw materials:

imatinib mesylate

4-[(4-methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]-benzamide L-(+)-tartrate

4-[(4-methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]-benzamide (D)-(-)-tartrate

4-[(4-methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]-benzamide vanillate

Refernces

A facile total synthesis of imatinib base and its analogues

10.1021/op700270n

The study presents an improved method for synthesizing Imatinib and its analogues. Imatinib is a tyrosine kinase inhibitor used to treat chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GISTs). The researchers developed a more cost-effective and environmentally friendly approach to synthesize Imatinib by avoiding the use of toxic cyanamide and expensive palladium compounds. Key chemicals involved include enaminone, guanidine nitrate, and copper salts. Enaminone reacts with guanidine nitrate to form pyrimidinyl amine, a crucial intermediate. Copper salts are used as catalysts in the C-N bond-forming reaction to produce another key intermediate. The nitro compound intermediate is reduced using a N2H4·H2O/FeCl3/C system. The final steps involve acylation and amination reactions to yield Imatinib base. This method achieves good yields and avoids hazardous reagents, making it suitable for industrial applications.

Synthesis of Imatinib by C-N Coupling Reaction of Primary Amide and Bromo-Substituted Pyrimidine Amine

10.1021/acs.oprd.9b00227

This study presents a new method for synthesizing Imatinib, a tyrosine kinase inhibitor used in treating chronic myeloid leukemia, through a C–N coupling reaction. The key chemicals involved include 4-(4-methylpiperazine-1-methyl)benzamide and N-(5-bromo-2-tolyl)-4-(3-pyridyl)pyrimidin-2-amine, which are coupled to form Imatinib. Nano-ZnO and KOH play crucial roles as catalysts in the hydrolysis of 4-(4-methylpiperazine-1-methyl)benzonitrile to produce the corresponding amide. The study highlights the efficiency and selectivity of nano-ZnO in this process. The new synthetic route avoids the production of genotoxic impurities, as classified by the FDA, and offers an environmentally friendly approach with a short reaction time and high purity of the final product.