Afatinib

Base Information

• Chemical Name: Afatinib
• CAS No.: 850140-72-6
• Molecular Formula: C24H25ClFN5O3
• Molecular Weight: 485.946
• Hs Code.: 29420000
• European Community (EC) Number: 810-720-4
• NSC Number: 750691
• UNII: 41UD74L59M
• DSSTox Substance ID: DTXSID20893451
• Nikkaji Number: J3.363.130H,J2.685.397D
• Wikipedia: Afatinib
• Wikidata: Q4688818
• NCI Thesaurus Code: C66940
• RXCUI: 1430438
• Pharos Ligand ID: L93TLR94JUC1
• Metabolomics Workbench ID: 61624
• ChEMBL ID: CHEMBL1173655
• Mol file: 850140-72-6.mol

Synonyms:(2E)-N-(4-(3-chloro-4-fluoroanilino)-7-(((3S)-oxolan-3-yl)oxy)quinoxazolin-6-yl)-4-(dimethylamino)but-2-enamide;afatinib;afatinib dimaleate;afatinib maleate;BIBW 2992;BIBW 2992 MA2;BIBW 2992MA2;BIBW-2992;BIBW-2992-MA2;BIBW-2992MA2;BIBW2992;BIBW2992 MA2;Gilotrif

Chemical Property of Afatinib

Chemical Property:

• Appearance/Colour: Off-White Solid
• Vapor Pressure: 0mmHg at 25°C
• Melting Point: 100 - 102 °C
• Boiling Point: 676.917°C at 760 mmHg
• PKA: 11.79±0.43(Predicted)
• Flash Point: 363.186°C
• PSA: 88.61000
• Density: 1.38g/cm3
• LogP: 4.53590
• Storage Temp.: -20°C
• Solubility.: Soluble in DMSO (up to 25 mg/ml) or in Ethanol (up to 25 mg/ml).
• XLogP3: 3.6
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 8
• Exact Mass: 485.1629955
• Heavy Atom Count: 34
• Complexity: 702

Purity/Quality:

98%, ^*data from raw suppliers

Afatinib ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: CN(C)CC=CC(=O)NC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=C(C=C3)F)Cl)OC4CCOC4
• 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
• Recent ClinicalTrials: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101)
• 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.
• Recent NIPH Clinical Trials: NEJ025B
• Description: Afatinib (850140-72-6) is a clinically useful kinase inhibitor approved for the treatment of non-small cell lung cancer. It is a potent and highly selective inhibitor of mutant and wild-type EGFR (IC50= 0.5 nM) and HER2 (IC50?= 14 nM).
• Uses: An aminocrotonylamino-substituted quinazoline derivative
• Clinical Use: Protein kinase inhibitor: Treatment of non-small cell lung cancer
• Drug interactions: Potentially hazardous interactions with other drugs Antipsychotics: avoid with clozapine - increased risk of agranulocytosis. Ciclosporin: concentration of afatinib possibly increased, separate administration by 6-12 hours. Tacrolimus: concentration of afatinib possibly increased, separate administration by 6-12 hours.

Technology Process of Afatinib

There total 42 articles about Afatinib 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: 98.0%

6-Amino-4-[(3-chloro-4-fluorophenyl)amino]-7-[(S)-(tetrahydrofuran-3-yl)oxy]quinazoline (314771-76-1,402855-03-2) + (E)-4-(dimethylamino)-2-butenoic acid methyl ester (212776-19-7) → afatinib (850140-72-6,1680184-59-1,945553-91-3,439081-17-1,439081-18-2)

Guidance literature:

6-Amino-4-[(3-chloro-4-fluorophenyl)amino]-7-[(S)-(tetrahydrofuran-3-yl)oxy]quinazoline; With trimethylaluminum; In hexane; dichloromethane; at 20 ℃; for 2h;

(E)-4-(dimethylamino)-2-butenoic acid methyl ester; In hexane; dichloromethane; at 60 ℃; for 5h; Solvent;

Reference yield: 97.7%

(S)-diethyl 2-(4-(3-chloro-4-fluorophenylamino)-7-(tetrahydrofuran-3-yloxy)quinazolin-6-ylamino)-2-oxoethylphosphonate (618061-76-0) + dimethylaminoacetaldehyde diethyl acetal (3616-56-6) → afatinib (850140-72-6,1680184-59-1,945553-91-3,439081-17-1,439081-18-2)

Guidance literature:

dimethylaminoacetaldehyde diethyl acetal; With hydrogenchloride; In water; at 20 - 30 ℃; Inert atmosphere;

(S)-diethyl 2-(4-(3-chloro-4-fluorophenylamino)-7-(tetrahydrofuran-3-yloxy)quinazolin-6-ylamino)-2-oxoethylphosphonate; With lithium chloride; potassium hydroxide; In tetrahydrofuran; at -15 - 20 ℃; for 2.5h; Product distribution / selectivity; Inert atmosphere;

Reference yield: 97.5%

6-Amino-4-[(3-chloro-4-fluorophenyl)amino]-7-[(S)-(tetrahydrofuran-3-yl)oxy]quinazoline (314771-76-1,402855-03-2) + trans-4-dimethylamino crotonic acid chloride hydrochloride salt (1055943-40-2) → afatinib (850140-72-6,1680184-59-1,945553-91-3,439081-17-1,439081-18-2)

Guidance literature:

In tetrahydrofuran; at 0 - 5 ℃;

upstream raw materials:

dimethylaminoacetaldehyde-hydrogen sulphite adduct

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

dimethylaminoacetaldehyde diethyl acetal

(E)-4-dimethylamino-but-2-enoic acid tert-butyl ester

Downstream raw materials:

2-butenamide, N-(4-((3-chloro-4-fluorophenyl)amino)-7-([(3S)-tetrahydro-3-furanyl]oxy)-6-quinazolinyl)-4-(dimethylamino)-, (2E)-, (2Z)-2-butenedioate

(2E)-N-[4-[(3-chloro-4-fluorophenyl)amino]-7-[[(3S)-tetrahydro-3-furanyl]oxy]-6-quinazolinyl]-4(dimethylamino)-2-butenamide dimaleate

afatinib citrate

afatinib fumarate

Refernces

• 1、 -. "PROCESS FOR THE PREPARATION OF N-[4-[(3-CHLORO-4-FLUORO PHENYL) AMINO]-7-[[(3s-TETRAHYDRO-3-FURANYL]OXY]-6-QUINAZOLINYL]-4-(DIMETHYL AMINO)-(2E)-2-BUTENAMIDE (2Z)-2-BUTENEDIOATE (1 :2) AND ITS POLYMORPHS THEREOF". . . Retrieved 2018/11/21.
• 2、 -. "A arab league law for nepal and its preparation method and application". Paragraph 0051; 0053; 0054; 0055; 0059; 0062; 0065; 0069. . Retrieved 2018/11/03.