Sitravatinib

Base Information

• Chemical Name: Sitravatinib
• CAS No.: 1123837-84-2
• Molecular Formula: C33H29F2N5O4S
• Molecular Weight: 629.687
• Mol file: 1123837-84-2.mol

Synonyms:Sitravatinib;N-(3-fluoro-4-((2-(5-(((2-methoxyethyl)amino)methyl)pyridin-2-yl)thieno[3,2-b]pyridin-7-yl)oxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide;MGCD-516

Chemical Property of Sitravatinib

Chemical Property:

• Boiling Point: 833.5±65.0 °C(Predicted)
• PKA: 13.17±0.70(Predicted)
• PSA: 142.71000
• Density: 1.417±0.06 g/cm3(Predicted)
• LogP: 7.05910
• Storage Temp.: -20°C
• Solubility.: Soluble in DMSO (up to at least 25 mg/ml), or in Ethanol (up to at least 25 mg/ml)

Purity/Quality:

98% ^*data from raw suppliers

MGCD 516 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

Useful:

• Description: Sitravatinib, known as MGCD516, is a multikinase (MET, RET, AXL, NTRK1, or NTRK3 genes) inhibitor used in a phase 1/1b clinical trial (NCT02219711) for patients with advanced cancers (NCT02219711). Sitravatinib is a multi-kinase inhibitor. It inhibits 35 kinases (IC50s = 0.5-5,550 nM) in a panel of 55 receptor tyrosine kinases (RTKs). Sitravatinib reduces proliferation of A-673, LPS141, MPNST, DDLS, and Saos-2 cancer cells (IC50s = 1,750, 340.1, 705.7, 266, and 1,830 nM, respectively) and decreases phosphorylation of insulin-like growth factor 1 receptor (IGF1-R), PDGFRβ, and Akt in these same cells when used at concentrations ranging from 62.5 to 4,000 nM. It decreases tumor growth in LPS141 and MPNST mouse xenograft models when administered at a dose of 15 mg/kg per day.
• Uses: MGCD 516 is an intermediate used to prepare substituted thienopyridines as inhibitors of protein tyrosine kinase activity.

Technology Process of Sitravatinib

There total 10 articles about Sitravatinib 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: 69.0%

tert-butyl ((6-(7-(2-fluoro-4-(1-((4-fluorophenyl)carbamoyl)cyclopropane-1-carboxamido)phenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl)(2-methoxyethyl)carbamate (1123837-39-7) → N'1-(3-fluoro-4-{[2-(5-{[(2-methoxyethyl)amino]methyl}pyridin-2-yl)thieno[3,2-b]pyridin-7-yl]oxy}phenyl)-N1-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (1123837-84-2)

Guidance literature:

With trifluoroacetic acid; In dichloromethane; at 20 ℃; for 18h;

Reference yield:

tert-butyl {[6-[7-(4-amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl]pyridin-3-yl]methyl}(2-methoxyethyl)carbamate (1123837-34-2) → N'1-(3-fluoro-4-{[2-(5-{[(2-methoxyethyl)amino]methyl}pyridin-2-yl)thieno[3,2-b]pyridin-7-yl]oxy}phenyl)-N1-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (1123837-84-2)

Guidance literature:

Multi-step reaction with 4 steps

1.1: triethylamine; thionyl chloride / tetrahydrofuran / 1 h / 5 °C

1.2: 3 h / 5 - 25 °C

2.1: pyridine; thionyl chloride / tetrahydrofuran / 1 h / 5 °C

3.1: potassium carbonate / tetrahydrofuran; water / 1 h / 5 °C

3.2: 3 h / 5 - 25 °C

4.1: hydrogenchloride; acetic acid / water / 1 h / 25 °C

With pyridine; hydrogenchloride; thionyl chloride; potassium carbonate; acetic acid; triethylamine; In tetrahydrofuran; water;

Reference yield:

tert-butyl {[6-(7-chlorothieno[3,2-b]pyridin-2-yl)pyridin-3-yl]methyl}(2-methoxyethyl)carbamate (1123838-02-7) → N'1-(3-fluoro-4-{[2-(5-{[(2-methoxyethyl)amino]methyl}pyridin-2-yl)thieno[3,2-b]pyridin-7-yl]oxy}phenyl)-N1-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (1123837-84-2)

Guidance literature:

Multi-step reaction with 5 steps

1.1: potassium tert-butylate / dimethyl sulfoxide / 0.5 h / 25 - 45 °C / Inert atmosphere

1.2: 2.17 h / 45 - 100 °C / Inert atmosphere

2.1: triethylamine; thionyl chloride / tetrahydrofuran / 1 h / 5 °C

2.2: 3 h / 5 - 25 °C

3.1: pyridine; thionyl chloride / tetrahydrofuran / 1 h / 5 °C

4.1: potassium carbonate / tetrahydrofuran; water / 1 h / 5 °C

4.2: 3 h / 5 - 25 °C

5.1: hydrogenchloride; acetic acid / water / 1 h / 25 °C

With pyridine; hydrogenchloride; thionyl chloride; potassium tert-butylate; potassium carbonate; acetic acid; triethylamine; In tetrahydrofuran; water; dimethyl sulfoxide;

upstream raw materials:

tert-butyl ((6-(7-(2-fluoro-4-(1-((4-fluorophenyl)carbamoyl)cyclopropane-1-carboxamido)phenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl)(2-methoxyethyl)carbamate

3-fluoro-4-hydroxybenzenaminium chloride

cyclopropane-1,1-dicarboxylic acid

1-(chlorocarbonyl)cyclopropane-1-carboxylic acid

Refernces

• 1、 -. "TREATMENT OF CANCER WITH ANTI-OX40 ANTIBODIES AND MULTI-KINASE INHIBITORS". Paragraph 0095-0099. . Retrieved 2021/05/29.
• 2、 -. "PROCESSES AND INTERMEDIATES FOR PREPARING FUSED HETEROCYCLIC KINASE INHIBITORS". Page/Page column 99; 100. . Retrieved 2009/04/25.