N-methyl-2-((1-acetyl-3-((1E)-2-(2-pyridinyl)ethenyl)-1H-indazol-6-yl)thio)benzamide

Base Information

• Chemical Name: N-methyl-2-((1-acetyl-3-((1E)-2-(2-pyridinyl)ethenyl)-1H-indazol-6-yl)thio)benzamide
• CAS No.: 1639137-80-6
• Molecular Formula: C₂₄H₂₀N₄O₂S
• Molecular Weight: 428.514
• Mol file: 1639137-80-6.mol

Synonyms:N-methyl-2-((1-acetyl-3-((1E)-2-(2-pyridinyl)ethenyl)-1H-indazol-6-yl)thio)benzamide

Chemical Property of N-methyl-2-((1-acetyl-3-((1E)-2-(2-pyridinyl)ethenyl)-1H-indazol-6-yl)thio)benzamide

Chemical Property:

• Melting Point: 214 - 215°C
• Density: 1.27±0.1 g/cm3(Predicted)

Purity/Quality:

99% ^*data from raw suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

Useful:

• Uses: N-Acetyl Axitinib is an intermediate used in the synthesis of Axitinib. Axitinib is a tyrosine kinase inhibitor that is also used in cancer therapy.

Technology Process of N-methyl-2-((1-acetyl-3-((1E)-2-(2-pyridinyl)ethenyl)-1H-indazol-6-yl)thio)benzamide

There total 6 articles about N-methyl-2-((1-acetyl-3-((1E)-2-(2-pyridinyl)ethenyl)-1H-indazol-6-yl)thio)benzamide 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: 99.0%

axitinib (319460-85-0,885126-40-9) + acetyl chloride (75-36-5) → N-methyl-2-((1-acetyl-3-((1E)-2-(2-pyridinyl)ethenyl)-1H-indazol-6-yl)thio)benzamide (1639137-80-6)

Guidance literature:

In dichloromethane; at 20 ℃; for 16h; Cooling with ice;

Reference yield:

6-Iodo-1H-indazole (261953-36-0) → N-methyl-2-((1-acetyl-3-((1E)-2-(2-pyridinyl)ethenyl)-1H-indazol-6-yl)thio)benzamide (1639137-80-6)

Guidance literature:

Multi-step reaction with 4 steps

1.1: 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; sodium hydrogencarbonate; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾ / 1-methyl-pyrrolidin-2-one / 0.5 h / 25 °C / Inert atmosphere; Large scale

1.2: 3 h / 25 - 50 °C / Inert atmosphere; Large scale

2.1: iodine; potassium hydroxide / 1-methyl-pyrrolidin-2-one; water / 5.5 h / 25 °C / Inert atmosphere; Large scale

3.1: N-ethyl-N,N-diisopropylamine; palladium diacetate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene / 1-methyl-pyrrolidin-2-one / 50 °C / Inert atmosphere; Large scale

4.1: 1-methyl-pyrrolidin-2-one / 50 - 90 °C / Inert atmosphere; Large scale

With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; iodine; palladium diacetate; sodium hydrogencarbonate; N-ethyl-N,N-diisopropylamine; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; potassium hydroxide; In 1-methyl-pyrrolidin-2-one; water; 1.1: |Stille Cross-Coupling (Migita-Kosugi-Stille Coupling) / 1.2: |Stille Cross-Coupling (Migita-Kosugi-Stille Coupling) / 4.1: |Heck Reaction;

DOI:10.1021/op400088k

Reference yield:

2-{(1H-indazol-6-yl)thio}-N-methylbenzamide (944835-85-2) → N-methyl-2-((1-acetyl-3-((1E)-2-(2-pyridinyl)ethenyl)-1H-indazol-6-yl)thio)benzamide (1639137-80-6)

Guidance literature:

Multi-step reaction with 3 steps

1: iodine; potassium hydroxide / 1-methyl-pyrrolidin-2-one; water / 5.5 h / 25 °C / Inert atmosphere; Large scale

2: N-ethyl-N,N-diisopropylamine; palladium diacetate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene / 1-methyl-pyrrolidin-2-one / 50 °C / Inert atmosphere; Large scale

3: 1-methyl-pyrrolidin-2-one / 50 - 90 °C / Inert atmosphere; Large scale

With iodine; palladium diacetate; N-ethyl-N,N-diisopropylamine; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; potassium hydroxide; In 1-methyl-pyrrolidin-2-one; water; 3: |Heck Reaction;

DOI:10.1021/op400088k

upstream raw materials:

6-Iodo-1H-indazole

2-{(1H-indazol-6-yl)thio}-N-methylbenzamide

2-((3-iodo-1H-indazol-6-yl)thio)-N-methylbenzamide

2-vinylpyridine

Downstream raw materials:

axitinib

Refernces

• 1、 -. "PRODRUGS OF THE TYROSINE KINASE INHIBITOR FOR TREATING CANCER". Paragraph 00144; 00146. . Retrieved 2021/03/05.