Cabozantinib Malate

Base Information

• Chemical Name: Cabozantinib Malate
• CAS No.: 1140909-48-3
• Molecular Formula: C28H24FN3O5.C4H6O5
• Molecular Weight: 635.603
• Mol file: 1140909-48-3.mol

Synonyms:Cabozantinib S-malate; Cabozantinib s-malate;XL 184;

Chemical Property of Cabozantinib Malate

Chemical Property:

• PSA: 193.61000
• LogP: 4.59340
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility.: DMSO (Slightly), Methanol (Slightly, Heated), Pyridine (Slightly)

Purity/Quality:

99.8% ^*data from raw suppliers

Cabozantinib L-Malate Salt ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Uses: Cabozantinib is a small molecule C-Met modulator. Cabozantinib acts as a potent multitargeted VEGFR2, Met, FLT3, Tie2, Kit and Ret inhibitor with IC50 of 0.035, 1.8, 14.4, 14.3 and 4.6 nM for VEGFR2, Met, FLT3, Tie2 and Kit, respectively. Cabozantinib shows dose-dependent inhibition of tumor growth and tumor regression, associated with disruption of the tumor vasculature and extensive tumor cell a poptosis. XL184 (Cabozantinib, BMS-907351) is a potent multitargeted VEGFR2, Met, FLT3, Tie2, Kit and Ret inhibitor with IC50 of 0.035, 1.8, 14.4, 14.3 and 4.6 nM for VEGFR2, Met, FLT3, Tie2 and Kit, respectively. Cabozantinib malate is the malate of Cabozantinib, a potent VEGFR2 inhibitor with IC50 of 0.035 nM and also inhibits c-Met, Ret, Kit, Flt-1/3/4, Tie2, and AXL with IC50 of 1.3 nM, 4 nM, 4.6 nM, 12 nM/11.3 nM/6 nM, 14.3 nM and 7 nM, respectively.
• Clinical Use: Cabozantinib (S)-malate (Cometriq?), which was discovered and developed by Exelixis, gained approval by the U.S. FDA in November 2012. The drug’s indication is for the treatment of medullary thyroid cancer (MTC), and is the second drug for this disease after AstraZeneca’s vandetanib (Caprelsa?). The drug was successfully launched on January 24, 2013. Cabozantinib inhibits multiple receptor tyrosine kinases including RET, MET, VEGFR-1, -2 and -3, KIT, TRKB, FLT-3, AXL, and TIE-2. It is currently also undergoing clinical trials for the treatment of prostate, ovarian, brain, melanoma, breast, non-small cell lung, pancreatic, hepatocellular and kidney cancers.

Technology Process of Cabozantinib Malate

There total 13 articles about Cabozantinib Malate 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: 92.26%

(S)-Malic acid (97-67-6,78644-42-5) + cabozantinib (849217-68-1) → Cabozantinib malate salt (1140909-48-3)

Guidance literature:

In tetrahydrofuran; at 50 - 70 ℃; Solvent; Large scale;

Reference yield:

(S)-Malic acid (97-67-6,78644-42-5) + N-(4-(6,7-dimethoxyquinolin-4-yloxy)phenyl)-N‘-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide hydrochloride → Cabozantinib malate salt (1140909-48-3)

Guidance literature:

N-(4-(6,7-dimethoxyquinolin-4-yloxy)phenyl)-N‘-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide hydrochloride; With sodium carbonate; In tetrahydrofuran; water; ethyl acetate; at 25 - 30 ℃; for 0.5h; Large scale;

(S)-Malic acid; With hydrogenchloride; In tetrahydrofuran; water; at 25 - 65 ℃; for 3h; Solvent; Temperature; Large scale;

Reference yield:

4-((6,7-dimethoxyquinolin-4-yl)oxy)aniline (190728-25-7) + 1-((4-fluorophenyl)carbamoyl)cyclopropane-1-carbonyl chloride + (S)-Malic acid (97-67-6,78644-42-5) → Cabozantinib malate salt (1140909-48-3)

Guidance literature:

4-((6,7-dimethoxyquinolin-4-yl)oxy)aniline; 1-[(4-fluorophenyl)carbamoyl]cyclopropane-1-carbonyl chloride; With potassium carbonate; In tetrahydrofuran; water; at 0 - 30 ℃; for 2h;

(S)-Malic acid; In 5,5-dimethyl-1,3-cyclohexadiene; water; at 25 - 75 ℃; for 1.16667h; Solvent; Temperature;

upstream raw materials:

(S)-Malic acid

cabozantinib

6,7-dimethoxyquinoline-4-ol

6,7-dimethoxy-4-chloroquinoline

Downstream raw materials:

cabozantinib

Refernces

• 1、 -. "POLYMORPHS OF N-(4-(6,7-DIMETHOXYQUINOLIN-4-YLOXY) PHENYL)-N'-(4-FLUOROPHENYL)CYCLOPROPANE-1, 1-DICARBOXAMIDE, (S)- MALATE, METHODS OF PRODUCTION AND PHARMACEUTICAL USES THEREOF". Page/Page column 19-21. . Retrieved 2020/05/19.
• 2、 -. "Method of Treating Cancer". Paragraph 0110; 0123-0124; 0126; 0146-0150. . Retrieved 2020/11/30.