Fruquintinib|HMPL-013

Base Information

• Chemical Name: Fruquintinib|HMPL-013
• CAS No.: 1194506-26-7
• Molecular Formula: C₂₁H₁₉N₃O₅
• Molecular Weight: 393.399
• Mol file: 1194506-26-7.mol

Synonyms:

Chemical Property of Fruquintinib|HMPL-013

Chemical Property:

• Boiling Point: 600.5±55.0 °C(Predicted)
• PKA: 14.35±0.46(Predicted)
• Density: 1.302±0.06 g/cm3(Predicted)
• Storage Temp.: Sealed in dry,Store in freezer, under -20°C
• Solubility.: Soluble in DMSO (up to 5 mg/ml).

Purity/Quality:

99% ^*data from raw suppliers

Fruquintinib(HMPL-013) >98% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

Useful:

• Description: Fruquintinib is a VEGFR inhibitor (IC50s = 33, 35, and 0.5 nM for VEGFR1, -2, and -3, respectively). It also inhibits RET, FGFR1, and c-Kit (IC50s = 128, 181, and 458 nM, respectively) in a panel of 253 kinases. Fruquintinib inhibits VEGF-A-induced proliferation of human umbilical vein endothelial cells (HUVECs) and VEGF-C-induced proliferation of human lymphatic endothelial cells (HLECs; IC50s = 1.7 and 4.2 nM, respectively). It decreases tube formation by HUVECs by 74 and 94% when used at concentrations of 30 and 300 nM, respectively. Fruquintinib (0.5-20 mg/kg per day for 21 days) reduces tumor growth in BGC-823, HT-29, Caki-1, and NCI H460 mouse xenograft models.
• Uses: Fruquintinib is a multi-targeted tyrosine kinase inhibitor, a third-line regimen involved in the treatment of advanced non-small cell lung cancer in humans. Fruquintinib is a potent, highly selective and orally active inhibitor of VEGFR1, 2, 3 tyrosine kinases.

Technology Process of Fruquintinib|HMPL-013

There total 6 articles about Fruquintinib|HMPL-013 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: 89.0%

6-hydroxy-2-methylbenzofuran-3-carboxylic acid methylamide (638217-08-0) + 6,7-dimethoxy-4-chloroquinazoline (13790-39-1) → 6-(6,7-dimethoxyquinazolin-4-yloxy)-N,2-dimethylbenzofuran-3-carboxamide (1194506-26-7)

Guidance literature:

In acetone; at 60 ℃; for 12h; Inert atmosphere;

Reference yield:

O-methylresorcine (150-19-6) → 6-(6,7-dimethoxyquinazolin-4-yloxy)-N,2-dimethylbenzofuran-3-carboxamide (1194506-26-7)

Guidance literature:

Multi-step reaction with 7 steps

1.1: N-Bromosuccinimide / N,N-dimethyl-formamide / 2 h / 30 °C

2.1: triethylamine / dichloromethane / 2 h / 30 °C

3.1: dibromobis(triphenylphosphine)nickel(II) / tetrahydrofuran / 1 h / 0 °C / Inert atmosphere

4.1: potassium tert-butylate / tetrahydrofuran / 2 h / 40 °C / Inert atmosphere

5.1: boron tribromide / dichloromethane / 1 h / 0 °C / Inert atmosphere

6.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 1 h / Inert atmosphere

6.2: 2 h / 0 - 25 °C / Inert atmosphere

7.1: acetone / 12 h / 60 °C / Inert atmosphere

With dibromobis(triphenylphosphine)nickel(II); N-Bromosuccinimide; potassium tert-butylate; boron tribromide; triethylamine; 1,1'-carbonyldiimidazole; In tetrahydrofuran; dichloromethane; N,N-dimethyl-formamide; acetone;

Reference yield:

2-bromo-5-methoxyphenol (63604-94-4) → 6-(6,7-dimethoxyquinazolin-4-yloxy)-N,2-dimethylbenzofuran-3-carboxamide (1194506-26-7)

Guidance literature:

Multi-step reaction with 6 steps

1.1: triethylamine / dichloromethane / 2 h / 30 °C

2.1: dibromobis(triphenylphosphine)nickel(II) / tetrahydrofuran / 1 h / 0 °C / Inert atmosphere

3.1: potassium tert-butylate / tetrahydrofuran / 2 h / 40 °C / Inert atmosphere

4.1: boron tribromide / dichloromethane / 1 h / 0 °C / Inert atmosphere

5.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 1 h / Inert atmosphere

5.2: 2 h / 0 - 25 °C / Inert atmosphere

6.1: acetone / 12 h / 60 °C / Inert atmosphere

With dibromobis(triphenylphosphine)nickel(II); potassium tert-butylate; boron tribromide; triethylamine; 1,1'-carbonyldiimidazole; In tetrahydrofuran; dichloromethane; acetone;

upstream raw materials:

6-hydroxy-2-methylbenzofuran-3-carboxylic acid methylamide

6,7-dimethoxy-4-chloroquinazoline

O-methylresorcine

2-bromo-5-methoxyphenol

Refernces

• 1、 -. "QUINAZOLINE DERIVATIVES". Page/Page column 5-6. . Retrieved 2009/12/04.