N-Desmethyl Imatinib

Base Information

• Chemical Name: N-Desmethyl Imatinib
• CAS No.: 404844-02-6
• Molecular Formula: C₂₈H₂₉N₇O
• Molecular Weight: 479.585
• Hs Code.: 29339900
• UNII: 6GOH0N63QD
• DSSTox Substance ID: DTXSID80193500
• Nikkaji Number: J1.690.778B
• Wikidata: Q27264884
• ChEMBL ID: CHEMBL3040018
• Mol file: 404844-02-6.mol

Synonyms:N-[4-Methyl-3-[4-(pyridin-3-yl)pyrimidin-2-ylamino]phenyl]-4-[(piperazin-1-yl)methyl]benzamide;Norimatinib;STI 509-00;Imatinib metabolite;

Chemical Property of N-Desmethyl Imatinib

Chemical Property:

• Appearance/Colour: Off-white to pale-yellow solid
• Melting Point: 99-101 °C
• Refractive Index: 1.676
• PKA: 13.28±0.70(Predicted)
• PSA: 95.07000
• Density: 1.269 g/cm³
• LogP: 4.66080
• Storage Temp.: -20°C Freezer
• XLogP3: 3
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 7
• Exact Mass: 479.24335857
• Heavy Atom Count: 36
• Complexity: 679

Purity/Quality:

98%,99%, ^*data from raw suppliers

N-DesmethylImatinib ^*data from reagent suppliers

Safty Information:

• Safety Statements: 24/25

MSDS Files:

Useful:

• Canonical SMILES: CC1=C(C=C(C=C1)NC(=O)C2=CC=C(C=C2)CN3CCNCC3)NC4=NC=CC(=N4)C5=CN=CC=C5
• Description: N-desmethyl Imatinib is a major active metabolite of imatinib , an anticancer agent that selectively targets tyrosine kinases, including Bcr-ABL, platelet-derived growth factor receptor (PDGFR), and KIT. N-desmethyl Imatinib is formed when imatinib undergoes demethylation by the cytochrome P450 (CYP) isomer CYP3A4. N-desmethyl Imatinib has the same in vitro potency at Bcr-ABL kinase as imatinib (IC50 = 38 nM for both) but is only present in plasma at 10-15% of the levels of imatinib, indicating the majority of the anticancer activity can be attributed to the parent compound.
• Uses: A metabolite of Gleevec, a tyrosine kinase inhibitor which is highly specific for BCR-ABL, the enzyme associated with chronic myelogenous leukemia (CML) and certain forms of acute lymphoblastic leukemia (ALL) aminoglycoside antibiotic similar to gentamycin, toxic to bacterial, yeast, higher plant and mammalian cells and to protozoans and helminthes anti-epileptic

Technology Process of N-Desmethyl Imatinib

There total 13 articles about N-Desmethyl 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: 86.0%

piperazine (110-85-0) + 4-(chloromethyl)-N-(4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]-amino}phenyl)benzamide (404844-11-7) → N-Desmethyl Imatinib (404844-02-6)

Guidance literature:

In N,N-dimethyl-formamide; at 20 ℃;

Reference yield: 84.0%

tert-butyl 4-(4-((4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)carbamoyl)benzyl)piperazine-1-carboxylate (1076199-23-9) → N-Desmethyl Imatinib (404844-02-6)

Guidance literature:

With trifluoroacetic acid; In dichloromethane; at 20 ℃; for 12h;

Reference yield:

6-methyl-1-N-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (152460-10-1) → N-Desmethyl Imatinib (404844-02-6)

Guidance literature:

Multi-step reaction with 2 steps

1: 1,4-dioxane / 2.75 h / 22 - 34 °C

2: ethanol; water / 14 h / Reflux

In 1,4-dioxane; ethanol; water;

DOI:10.1016/j.bmc.2013.03.038

upstream raw materials:

piperazine

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

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

p-(chloromethyl)benzoyl chloride

Downstream raw materials:

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

4-[[4-(methyl-d3)-1-piperazinyl]methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-phenyl]benzamide

Refernces

• 1、 Yang, Yiqing,Gao, Hongying,Sun, Xiuyun,Sun, Yonghui,Qiu, Yueping,Weng, Qinjie,Rao, Yu. "Global PROTAC Toolbox for Degrading BCR-ABL Overcomes Drug-Resistant Mutants and Adverse Effects". . p. 8567 - 8583. Retrieved 2020/09/16.
• 2、 -. "A novel structure of the kinase inhibitors". Paragraph 0132; 0134. . Retrieved 2018/06/07.