Icotinib

Base Information

• Chemical Name: Icotinib
• CAS No.: 610798-31-7
• Molecular Formula: C22H21N3O4
• Molecular Weight: 391.42
• Hs Code.: 29339900
• Mol file: 610798-31-7.mol

Synonyms:N-(3-ETHYNYLPHENYL)-7,8,10,11,13,14-HEXAHYDRO-[1,4,7,10]TETRAOXACYCLODODECINO[2,3-G]QUINAZOLIN-4-AMINE

Chemical Property of Icotinib

Chemical Property:

• Boiling Point: 581℃
• PKA: 5.32±0.20(Predicted)
• Flash Point: 305℃
• PSA: 74.73000
• Density: 1.31
• LogP: 3.23210
• Solubility.: insoluble in H2O; ≥129.6 mg/mL in DMSO; ≥14.13 mg/mL in EtOH with ultrasonic

Purity/Quality:

98%,99%, ^*data from raw suppliers

Icotinib ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Uses: Icotinib is a highly selective, 1st generation EGFR-TKI (epidermal growth factor receptor tyrosine kinase) inhibitor. The mutations of EGFR is associated with many kinds of cancers. Currently, Icotinib is under investigation for its treatment efficacy on some cancer such as non-small cell lung cancer. Icotinib take effects through binding reversibly to the ATP binding site of the EGFR protein, further preventing completion of the signal transduction cascade. Icotinib is a potent and specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with IC50 of 5 nM.
• Description: Icotinib is also known as ConMana. It is a highly selective, first-generation inhibitor of epidermal growth factor receptor tyrosine kinase (EGFR-TKI), whose mutation and overexpression is involved in many kinds of cancer. Icotinib is a quinazoline derivative that binds reversibly to the ATP binding site of the EGFR protein, being capable of blocking the signal transduction cascade. It is currently under investigation for its treatment efficacy on the EGFR+ Non-small cell lung cancer.
• Indications: Icotinib (Conmana?, BetaPharma), an EGFR inhibitor, was approved by the China State FDA in 2011 for the treatment of NSCLC. Icotinib resembles erlotinib in possessing the N-(3-ethylnylphenyl) quinazolin-4-amine core scaffold of erlotinib that binds to the EGFR ATP pocket. An adjacent hydrophobic group was also retained while the solvent exposed two 2-methoxyethyoxysubstituents at the 6- and 7-positions of the quinazoline core were cyclized to afford the tetraoxacyclododecene moiety of icotinib. Efficacy and safety of icotinib as first-line therapy in patients has been evaluated for advanced NSCLC in recent clinical studies.

Technology Process of Icotinib

There total 24 articles about Icotinib 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: 95.0%

N-(3-ethynylphenyl)-6,7-difluoroquinazolin-4-amine + 2,2'-[1,2-ethanediylbis(oxy)]bisethanol (112-27-6) → N-(3-ethynylphenyl)-7,8,10,11,13,14-hexahydro-[1,4,7,10]tetraoxacyclododecino[2,3-g]quinazolin-4-amine (610798-31-7)

Guidance literature:

With sodium hydride; In dichloromethane; at 60 ℃; for 24h; Solvent; Reagent/catalyst; Temperature; Cooling with ice;

Reference yield: 72.0%

4-chloro-7,8,10,11,13,14-hexahydro-6,9,12,15-tetraoxa-1,3-diaza-cyclododeca[b]naphthalene (1204313-58-5) + 3-acetylenephenylamine (54060-30-9) → N-(3-ethynylphenyl)-7,8,10,11,13,14-hexahydro-[1,4,7,10]tetraoxacyclododecino[2,3-g]quinazolin-4-amine (610798-31-7)

Guidance literature:

In N,N-dimethyl-formamide; isopropyl alcohol;

DOI:10.1016/j.bmcl.2012.06.067

Reference yield:

triethylene glycol di-(p-toluenesulfonate) (19249-03-7) → N-(3-ethynylphenyl)-7,8,10,11,13,14-hexahydro-[1,4,7,10]tetraoxacyclododecino[2,3-g]quinazolin-4-amine (610798-31-7)

Guidance literature:

Multi-step reaction with 5 steps

1: potassium carbonate / acetonitrile / Reflux

2: nitric acid; sulfuric acid / acetic acid / 20 - 30 °C

3: acetic acid; iron / methanol / Reflux

4: 1,4-dioxane / 11 - 12 h / Reflux

5: acetic acid / 100 °C

With sulfuric acid; nitric acid; iron; potassium carbonate; acetic acid; In 1,4-dioxane; methanol; acetic acid; acetonitrile;

upstream raw materials:

trimethylsilylacetylene

C₁₄H₁₇NO₈

3,4-dihydroxybenzoic acid methyl ester

C₁₄H₁₉NO₆

Refernces

• 1、 -. "Quinolinamine compound with IDO1 inhibition function and preparation method thereof". Paragraph 0044-0046. . Retrieved 2020/11/23.
• 2、 -. "Eck for nepal and hydrochloric acid eck for nepal preparation method and wherein intermediate". Paragraph 0075; 00107; 00108; 00109; 00111; 00113; 00115. . Retrieved 2018/06/28.