Dacomitinib

Base Information

• Chemical Name: Dacomitinib
• CAS No.: 1110813-31-4
• Deprecated CAS: 1006885-28-4
• Molecular Formula: C24H25ClFN5O2
• Molecular Weight: 469.94
• Hs Code.: 29335990
• UNII: 2XJX250C20
• ChEMBL ID: CHEMBL2110732
• DSSTox Substance ID: DTXSID50149493
• Metabolomics Workbench ID: 153035
• NCI Thesaurus Code: C171723
• Nikkaji Number: J3.341.567B
• Pharos Ligand ID: PSP3LBW32FKK
• RXCUI: 2058848
• Wikidata: Q17130597
• Wikipedia: Dacomitinib
• Mol file: 1110813-31-4.mol

Synonyms:dacomitinib;N-(4-(3-chloro-4-fluoroanilino)-7-methoxy-6-quinazolinyl)-4-(1-piperidinyl)-2-butenamide;PF 00299804;PF-00299804;PF00299804;Vizimpro

Chemical Property of Dacomitinib

Chemical Property:

• Appearance/Colour: White to Off-White Solid
• Melting Point: >187°C (dec.)
• Boiling Point: 665.7±55.0 °C(Predicted)
• PKA: 12.05±0.43(Predicted)
• PSA: 79.38000
• Density: 1.344
• LogP: 5.23900
• Storage Temp.: Refrigerator
• Solubility.: DMSO (Slightly), Methanol (Slightly, Heated)
• XLogP3: 4.4
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 7
• Exact Mass: 469.1680809
• Heavy Atom Count: 33
• Complexity: 665

Purity/Quality:

99%min ^*data from raw suppliers

Dacomitinib ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: COC1=C(C=C2C(=C1)N=CN=C2NC3=CC(=C(C=C3)F)Cl)NC(=O)C=CCN4CCCCC4
• Isomeric SMILES: COC1=C(C=C2C(=C1)N=CN=C2NC3=CC(=C(C=C3)F)Cl)NC(=O)/C=C/CN4CCCCC4
• Recent ClinicalTrials: Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) PRIME Trial
• Recent EU Clinical Trials: ERIS- EGFR-Mutated Lung Cancer in Randomized Investigator-Initiated Study
• Recent NIPH Clinical Trials: A phase II study to evaluate prophylactic treatment of dacomitinib-induced dermatologic adverse events in EGFR-mutated advanced non-small cell lung cancer
• Description: Dacomitinib is a selective and irreversible inhibitor of EGFR. It is a drug candidate for the treatment of non-small cell lung carcinoma. It is current under the Phase III clinical trials. It also shows potential for the treatment of HER-2 amplified breast cancer cells lines that are resistant to trastuzumab and lapatinib. The epidermal growth factor receptors (EGFR), whose members include ErbB1 (HER1), ErbB2 (HER2), ErbB3 (HER3), and ErbB4 (HER4), are receptor tyrosine kinases that are often over-expressed in cancer. PF-299804 is a second generation pan-ErbB receptor tyrosine kinase inhibitor (IC50s = 6, 45.7, and 73.7 nM for ErbB1, ErbB2, and ErbB4, respectively) that irreversibly binds to the ATP site in the catalytic domains of ErbB receptors. At 15 mg/kg, it demonstrates antitumor activity ranging from delay in tumor growth to complete regression in various tumor xenograft models expressing either wild-type ErbB or mutant ErbB family members that show resistance to first generation ErbB kinase inhibitors.
• Uses: Dacomitinib (PF299804), which name is (E)-N-[4-(3-chloro-4-fluoroanilino)-7- methoxyquinazolin-6-yl]-4-piperidin-1-ylbut-2-enamide, is a potent, orally available, highly selective, irreversible small-molecule tyrosine kinase inhibitor (TKI) of tyrosine kinase human epidermal growth factor receptors (HER) 1 (EGFR), HER2, and HER4. It is most effective against EGFR with IC50 of 6 nM. It is highly effective against NSCLCs carrying EGFR or ERBB2 mutant (anti-Gefitinib) and EGFR T790M mutant. Dacomitinib is an Erb-inhibitor, or an inhibitor of the members of the epidermal growth factor receptor family. Used as an ant-cancer agent due to observation of over-expressed epidermal growth factor receptor in nearly all cases of squamous cell carcinoma in the head and neck.

Technology Process of Dacomitinib

There total 42 articles about Dacomitinib 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: 90.08%

3-chloro-4-fluorophenylamine (367-21-5) + (E)-N-(5-cyano-4-(((E)-(dimethylamino)methylene)amino)-2-methoxyphenyl)-4-(piperidin-1-yl)but-2-enamide → Dacomitinib (1110813-31-4)

Guidance literature:

With acetic acid; at 40 ℃;

Reference yield: 89.0%

C33H35ClFN5O4 → Dacomitinib (1110813-31-4)

Guidance literature:

C₃₃H₃₅ClFN₅O₄; With trifluoroacetic acid; at 3 ℃; for 24h;

With sodium hydroxide; In water;

Reference yield: 86.6%

3-chloro-4-fluorophenylamine (367-21-5) + C18H21ClN4O2 → Dacomitinib (1110813-31-4)

Guidance literature:

With triethylamine; In tetrahydrofuran; at 20 ℃; for 1h;

upstream raw materials:

3-chloro-4-fluorophenylamine

N'-(2-cyano-5-methoxy-4-nitrophenyl)-N,N-dimethylmethanimidamide

4-methoxyanthranilic acid

Refernces

• 1、 -. "Preparation method of dacomitinib intermediate". . . Retrieved 2021/04/28.
• 2、 -. "Preparation method of dacotinib". . . Retrieved 2022/01/10.