Tivantinib

Base Information

• Chemical Name: Tivantinib
• CAS No.: 905854-02-6
• Deprecated CAS: 1228508-24-4,1000873-98-2
• Molecular Formula: C23H19 N3 O2
• Molecular Weight: 369.423
• European Community (EC) Number: 805-160-2
• UNII: PJ4H73IL17
• ChEMBL ID: CHEMBL2103882
• DSSTox Substance ID: DTXSID60920316
• Metabolomics Workbench ID: 153233
• NCI Thesaurus Code: C62437
• Nikkaji Number: J3.496.311H
• Pharos Ligand ID: BWMN85DDDHS4
• Wikidata: Q17123902
• Wikipedia: Tivantinib
• Mol file: 905854-02-6.mol

Synonyms:(-)-trans-3-(5,6-dihydro-4H-pyrrolo(3,2,1-ij)quinolin-1-yl)-4-(1H-indol-3-yl)pyrrolidin-2,5-dione;ARQ 197;ARQ-197;ARQ197;tivantinib

Chemical Property of Tivantinib

Chemical Property:

• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.797
• Boiling Point: 715.95°C at 760 mmHg
• PKA: 9.28±0.70(Predicted)
• Flash Point: 386.793°C
• PSA: 66.89000
• Density: 1.49
• LogP: 3.92140
• Storage Temp.: -20°C Freezer, Under inert atmosphere
• Solubility.: DMSO (Slightly), Methanol (Slightly)
• XLogP3: 2.9
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 2
• Exact Mass: 369.147726857
• Heavy Atom Count: 28
• Complexity: 666

Purity/Quality:

99% ^*data from raw suppliers

Tivantinib ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1CC2=C3C(=CC=C2)C(=CN3C1)C4C(C(=O)NC4=O)C5=CNC6=CC=CC=C65
• Isomeric SMILES: C1CC2=C3C(=CC=C2)C(=CN3C1)[C@H]4[C@@H](C(=O)NC4=O)C5=CNC6=CC=CC=C65
• Recent ClinicalTrials: TIvantinib as Maintenance Treatment in Extended Small-cell Lung Cancer (TIMES)
• Recent EU Clinical Trials: TIvantinib as Maintenance treatment in Extended Small-cell lung cancer (TIMES)
• Recent NIPH Clinical Trials: A Phase III trial of ARQ 197 in hepatocellular carcinoma (HCC)
• Uses: Tivantinib is a hepatocyte growth factor receptor (proto-oncogene c-Met; MET) inhibitor. Tivantinib inhibits human c-Met receptor tyrosine kinase selectively and is a promising therapeutic option fo r the treatment of c-Met-associated cancers. Tivantinib is a hepatocyte growth factor receptor (proto-oncogene c-Met; MET) inhibitor. Tivantinib inhibits human c-Met receptor tyrosine kinase selectively and is a promising therapeutic option for the treatment of c-Met-associated cancers. Potent c-MET inhibitor.

Technology Process of Tivantinib

There total 15 articles about Tivantinib 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:

(3R,4R)-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)pyrrolidine-2,5-dione pseudoephedrine complex (1313508-66-5) → Tivantinib (905854-02-6,1000873-98-2,1239986-50-5)

Guidance literature:

With hydrogenchloride; In 3-methyltetrahydrofuran; water; at 50 ℃; pH=1.6; Product distribution / selectivity;

Reference yield:

(±)-trans-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)pyrrolidine-2,5-dione (1000873-98-2,1239986-50-5) → (+)-3(S),4(S)-3-(5,6-dihydro-4H-pyrrolo[3,2,1-j]quinolin-1-yl)-4-(1H-indol-3-yl)pyrrolidine-2,5-dione (905854-03-7,1000873-98-2,1239986-50-5) + Tivantinib (905854-02-6,1000873-98-2,1239986-50-5)

Guidance literature:

Purification / work up; Resolution of racemate;

Reference yield:

5,6-dihydro-4H-pyrrolo-[3,2,1-ij]quinoline (5840-01-7) → Tivantinib (905854-02-6,1000873-98-2,1239986-50-5)

Guidance literature:

Multi-step reaction with 5 steps

1.1: tert-butyl methyl ether / 2.17 h / 15 - 32 °C / Industry scale

1.2: 2 h / Industry scale

2.1: potassium tert-butylate / tetrahydrofuran / 3 h / 20 - 32 °C / Industry scale

2.2: 0.5 h / 40 - 50 °C / Industry scale

2.3: 40 °C / pH 8 - 9 / Industry scale

3.1: hydrogen; potassium tert-butylate / 20 % Pd(OH)2/C / tetrahydrofuran / 45 - 55 °C / 3361.55 - 4137.29 Torr / Industry scale

4.1: hydrogenchloride / water; Isopropyl acetate / Industry scale

5.1: Chiralpak AZ column / dichloromethane; acetonitrile; methanol / Resolution of racemate; Multicolumn chromatography

With hydrogenchloride; potassium tert-butylate; hydrogen; 20 % Pd(OH)2/C; In tetrahydrofuran; methanol; dichloromethane; tert-butyl methyl ether; Isopropyl acetate; water; acetonitrile;

upstream raw materials:

(±)-trans-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)pyrrolidine-2,5-dione

5,6-dihydro-4H-pyrrolo-[3,2,1-ij]quinoline

(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)oxoacetic acid methyl ester

3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dion

Refernces

• 1、 -. "Highly Pure Pyrroloquinolinyl-Pyrrole-2,5-Dione and Pyrroloquinolinyl-Pyrrolidine-2,5-Dione and Methods of Preparing Same". . . Retrieved 2013/11/05.
• 2、 -. "MELEIMIDE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND METHODS FOR TREATMENT OF CANCER". Page/Page column 57. . Retrieved 2008/06/13.