Lapatinib

Base Information

• Chemical Name: Lapatinib
• CAS No.: 231277-92-2
• Molecular Formula: C29H26ClFN4O4S
• Molecular Weight: 581.067
• Hs Code.: 29349990
• European Community (EC) Number: 642-915-3,878-720-7
• NSC Number: 745750
• UNII: 0VUA21238F
• DSSTox Substance ID: DTXSID7046675
• Nikkaji Number: J1.859.987B
• Wikipedia: Lapatinib
• Wikidata: Q420323
• NCI Thesaurus Code: C26653
• RXCUI: 480167
• Pharos Ligand ID: 3GTG4JMBXQKW
• Metabolomics Workbench ID: 43465
• ChEMBL ID: CHEMBL554
• Mol file: 231277-92-2.mol

Synonyms:GW 282974X;GW 572016;GW-282974X;GW-572016;GW282974X;GW572016;lapatinib;lapatinib ditosylate;N-(3-chloro-4-(((3-fluorobenzyl)oxy)phenyl)-6-(5-(((2-methylsulfonyl)ethyl)amino)methyl) -2-furyl)-4-quinazolinamine;Tykerb

Chemical Property of Lapatinib

Chemical Property:

• Appearance/Colour: Powder
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.645
• Boiling Point: 750.7 °C at 760 mmHg
• PKA: 6.34±0.19(Predicted)
• Flash Point: 407.8 °C
• PSA: 114.73000
• Density: 1.381 g/cm³
• LogP: 7.68380
• Storage Temp.: 2-8°C(protect from light)
• Solubility.: Soluble in DMSO (up to 200 mg/ml)
• XLogP3: 5.1
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 9
• Rotatable Bond Count: 11
• Exact Mass: 580.1347324
• Heavy Atom Count: 40
• Complexity: 898

Purity/Quality:

99%, ^*data from raw suppliers

Lapatinib, Free Base ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T,F
• Hazard Codes: T,F

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: CS(=O)(=O)CCNCC1=CC=C(O1)C2=CC3=C(C=C2)N=CN=C3NC4=CC(=C(C=C4)OCC5=CC(=CC=C5)F)Cl
• Recent ClinicalTrials: LOGiC - Lapatinib Optimization Study in ErbB2 (HER2) Positive Gastric Cancer: A Phase III Global, Blinded Study Designed to Evaluate Clinical Endpoints and Safety of Chemotherapy Plus Lapatinib
• Recent EU Clinical Trials: The ROME trial from histology to target: the road to personalize target therapy and immunotherapy
• Recent NIPH Clinical Trials: DS-8201a in Pre-treated HER2 Breast Cancer That Cannot be Surgically Removed or Has Spread [DESTINY-Breast02]
• Description: Lapatinib, a new member of the 4-anilinoquinazoline class of RTK inhibitors (RTKIs), was launched as an oral treatment for breast cancer. Lapatinib has dual affinity for EGFR and HER2 tyrosine kinases. It is indicated in combination with capecitabine for treating patients with advanced or metastatic breast cancer whose tumors overexpress HER2 and who have received prior therapy including an anthracycline, a taxane, and trastuzumab. Previously marketed drugs from the 4-anilinoquinazoline class include erlotinib (Tarceva) and gefitinib (IressaTM), both of which are indicated for treating non-small-cell lung cancer (NSCLC). As with erlotinib and gefitinib, To Market, To Market 2007 475 lapatinib is an ATP-competitive kinase inhibitor. It inhibits the tyrosine kinase activity EGFR and HER-2 with apparent Ki values of 3 and 13 nM, respectively, and has slow off-rate kinetics (t1/2X300 min). In addition, dividing the daily dose of lapatinib results in approximately 2-fold higher exposure at steady state compared to the same total dose administered once daily.The chemical synthesis of lapatinib entails the condensation of 4-chloro-6-iodoquinazoline and 3-chloro-4-(3-fluorobenzyloxy)aniline to produce a diaryl amine intermediate followed by Stille coupling of the iodo group with 5-dioxolanyl-2-(tributylstannyl)furan and subsequent acid hydrolysis of the cyclic ketal to the corresponding aldehyde. Finally, reductive amination of the aldehyde intermediate with 2-(methanesulfonyl) ethylamine in the presence of sodium triacetoxyborohydride produces lapatinib. .
• Uses: Lapatinib, used in the form of Lapatinib Ditosylate, is a potent EGFR and ErbB2 inhibitor with IC50 of 10.8 and 9.2 nM, respectively. antineoplastic, tyrosine kinase inhibitor An antineoplastic agent used in breast cancer research
• Clinical Use: #N/A
• Drug interactions: Potentially hazardous interactions with other drugs Antibacterials: avoid with rifabutin, rifampicin and telithromycin. Antidepressants: avoid with St John’s wort. Antidiabetics: avoid with repaglinide. Antiepileptics: concentration reduced by carbamazepine - avoid; possibly reduced fosphenytoin and phenytoin concentration - avoid. Antifungals: concentration increased by ketoconazole - avoid; avoid with itraconazole, posaconazole and voriconazole. Antipsychotics: avoid with clozapine (increased risk of agranulocytosis); avoid with pimozide. Antivirals: avoid with boceprevir, ritonavir and saquinavir. Cytotoxics: concentration of pazopanib increased; possible increased risk of neutropenia with docetaxel and paclitaxel; concentration of active metabolite of irinotecan increased, consider reducing irinotecan dose. Grapefruit juice: avoid concomitant us

Technology Process of Lapatinib

There total 71 articles about Lapatinib 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: 100.0%

2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4) + 5-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl)furan-2-carbaldehyde (231278-84-5) → lapatanib (231277-92-2)

Guidance literature:

2-(methylsulfonyl)ethylamine hydrochloride; With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 20 ℃; for 0.333333h;

5-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl)furan-2-carbaldehyde; With acetic acid; In tetrahydrofuran; at 40 ℃; for 2h;

With sodium tris(acetoxy)borohydride; In tetrahydrofuran; at 25 - 40 ℃; for 3h; Concentration;

Reference yield: 97.0%

C27H19ClFN3O3 + 2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4) → lapatanib (231277-92-2)

Guidance literature:

With triethylamine; In dichloromethane; at 25 - 30 ℃; Inert atmosphere;

Reference yield: 90.3%

formaldehyd (50-00-0,30525-89-4,61233-19-0) + 6-(furan-2-yl)-4-[3-chloro-4-(3-fluorobenzyloxy)phenyl]aminoquinazoline + 2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4) → lapatanib (231277-92-2)

Guidance literature:

In tetrahydrofuran; at 35 - 40 ℃; for 4h;

upstream raw materials:

2-Methanesulfonyl-ethylamine

5-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl)furan-2-carbaldehyde

3-chloro-4-(3-fluorobenzyloxy)nitrobenzene

4-chloro-6-iodoquinazoline

Downstream raw materials:

lapatinib monobesylate

lapatinib ditosylate

5-{4-[3-chloro-4-(3-fluorobenzyloxy)phenylamino]quinazolin-6-yl}furan-2-ylmethyl-(2-methanesulfonylethyl)carbamic acid tert-butyl ester

Refernces

• 1、 -. "Preparation method of 6-substituted furanyl-4-substituted aminoquinazoline derivative and key intermediate thereof". Paragraph 0107; 0110-0111. . Retrieved 2020/02/14.
• 2、 -. "A process for preparing the lapatinib method and intermediate (by machine translation)". . . Retrieved 2018/04/03.