(S,E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-((tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(dimethylamino)but-2-enamide maleate

Base Information

• Chemical Name: (S,E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-((tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(dimethylamino)but-2-enamide maleate
• CAS No.: 850140-73-7
• Molecular Formula: 2C₄H₄O₄*C₂₄H₂₅ClFN₅O₃
• Molecular Weight: 718.092
• Hs Code.: 29339900
• European Community (EC) Number: 810-416-1
• Mol file: 850140-73-7.mol

Synonyms:850140-73-7;(S,E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-((tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(dimethylamino)but-2-enamide maleate;SCHEMBL20533352

Chemical Property of (S,E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-((tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(dimethylamino)but-2-enamide maleate

Chemical Property:

• Boiling Point: 983.1 °C at 760 mmHg
• Flash Point: 548.3 °C
• PSA: 241.30000
• LogP: 4.53600
• Storage Temp.: Refrigerator
• Solubility.: DMSO (Slightly), Methanol (Slightly)
• Hydrogen Bond Donor Count: 4
• Hydrogen Bond Acceptor Count: 12
• Rotatable Bond Count: 10
• Exact Mass: 601.1739541
• Heavy Atom Count: 42
• Complexity: 821

Purity/Quality:

95.0-99.0%(min) ^*data from raw suppliers

AfatinibDimaleate ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CN(C)CC=CC(=O)NC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=C(C=C3)F)Cl)OC4CCOC4.C(=CC(=O)O)C(=O)O
• Isomeric SMILES: CN(C)C/C=C/C(=O)NC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=C(C=C3)F)Cl)O[C@H]4CCOC4.C(=C\C(=O)O)\C(=O)O
• Recent EU Clinical Trials: AFAMOSI: Prospective, randomized, multicenter Phase IV study to evaluate the efficacy and safety of afatinib followed by osimertinib compared to osimertinib in patients with EGFRmutated/T790M Mutation negative non-squamous NSCLC in the first-line setting.
• Description: Afatinib dimaleate (Tovok; BIBW2992; Gilotrif) is a salt form of Afatinib. Afatinib is a second-generation, orally administered, irreversible inhibitor of the ErbB family of tyrosine kinases. Afatinib dimaleate was approved by the U.S. Food and Drug Administration (FDA) in 2013 for the treatment of non-small cell lung cancer (NSCLC). Specifically, it was approved for patients presenting with metastatic NSCLC tumors which contain epidermal growth factor receptor (EGFR) exon deletions or exon 21 mutations. Afatinib dimaleate is a covalent inhibitor of ErbB tyrosine kinases (tyk), which downregulates ErbB signaling by irreversible binding of EGFR tyk binding sites. While no manufacturing route has been disclosed to date, the most scalable published route likely derives from two Boehringer Ingelheim patents.
• Uses: Afatinib Dimaleate is a salt of Afatinib {BIBW 2992), an aminocrotonylamino-substituted quinazoline derivative used for treating cancer and diseases of the respiratory tract, lungs, gastrointestinal tract, bile duct, and gallbladder. An anilino-quinazoline that irreversibly inhibits EGFR and HER2 kinase activity.

Technology Process of (S,E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-((tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(dimethylamino)but-2-enamide maleate

There total 25 articles about (S,E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-((tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(dimethylamino)but-2-enamide maleate 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: 96.5%

afatinib (850140-72-6,1680184-59-1,945553-91-3,439081-17-1,439081-18-2) + maleic acid (110-16-7,26099-09-2) → 2-butenamide, N-(4-((3-chloro-4-fluorophenyl)amino)-7-([(3S)-tetrahydro-3-furanyl]oxy)-6-quinazolinyl)-4-(dimethylamino)-, (2E)-, (2Z)-2-butenedioate (850140-73-7)

Guidance literature:

In tetrahydrofuran; at 20 ℃; Solvent; Temperature; Concentration;

Reference yield: 94.1%

afatinib (850140-72-6,1680184-59-1,945553-91-3,439081-17-1,439081-18-2) + maleic acid (110-16-7,26099-09-2) → (2E)-N-[4-[(3-chloro-4-fluorophenyl)amino]-7-[[(3S)-tetrahydro-3-furanyl]oxy]-6-quinazolinyl]-4(dimethylamino)-2-butenamide dimaleate (850140-73-7)

Guidance literature:

In ethanol; at 70 ℃;

Reference yield: 90.0%

4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-buten-1-yl]amino}-7-[(S)-(tetrahydrothran-3-yl)oxy]quinazoline (1680184-59-1,945553-91-3,439081-17-1,439081-18-2) + maleic acid (110-16-7,26099-09-2) → 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-butene-1-yl]amino}-7-((S)-tetrahydrofuran-3-yloxy)quinazoline dimaleate salt (850140-73-7)

Guidance literature:

In ethanol; at 70 ℃;

upstream raw materials:

afatinib

maleic acid

(S)-diethyl 2-(4-(3-chloro-4-fluorophenylamino)-7-(tetrahydrofuran-3-yloxy)quinazolin-6-ylamino)-2-oxoethylphosphonate

6-Amino-4-[(3-chloro-4-fluorophenyl)amino]-7-[(S)-(tetrahydrofuran-3-yl)oxy]quinazoline

Refernces

• 1、 -. "The second maleic acid arab league law for nepal preparation method". Paragraph 0037-0041. . Retrieved 2019/05/15.
• 2、 -. "Preparation method of afatinib maleate". Paragraph 0026; 0039; 0040; 0041. . Retrieved 2019/12/25.