Erlotinib hydrochloride

Base Information

• Chemical Name: Erlotinib hydrochloride
• CAS No.: 183319-69-9
• Molecular Formula: C22H24ClN3O4
• Molecular Weight: 429.903
• Hs Code.: 29335990
• European Community (EC) Number: 620-491-0
• NSC Number: 718781
• UNII: DA87705X9K
• DSSTox Substance ID: DTXSID10171412
• Wikidata: Q27124083
• NCI Thesaurus Code: C2693
• RXCUI: 477320
• Pharos Ligand ID: NUXHNF3XHDN6
• ChEMBL ID: CHEMBL1079742
• Mol file: 183319-69-9.mol

Synonyms:11C erlotinib;11C-erlotinib;358,774, CP;358774, CP;CP 358,774;CP 358774;CP-358,774;CP-358774;CP358,774;CP358774;erlotinib;erlotinib HCl;erlotinib hydrochloride;HCl, Erlotinib;Hydrochloride, Erlotinib;N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine;OSI 774;OSI-774;OSI774;Tarceva

Chemical Property of Erlotinib hydrochloride

Chemical Property:

• Appearance/Colour: White or off-white powder
• Vapor Pressure: 4.52E-12mmHg at 25°C
• Melting Point: 223-225 °C
• Boiling Point: 553.6 °C at 760 mmHg
• PKA: pKa (25°): 5.42
• Flash Point: 288.6 °C
• PSA: 74.73000
• LogP: 4.28010
• Storage Temp.: -20°C Freezer
• Solubility.: Soluble in DMSO (up to 18 mg/ml with warming).
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 11
• Exact Mass: 429.1455339
• Heavy Atom Count: 30
• Complexity: 525

Purity/Quality:

99%, ^*data from raw suppliers

Erlotinib Hydrochloride ^*data from reagent suppliers

Safty Information:

• Safety Statements: 24/25

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: COCCOC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC=CC(=C3)C#C)OCCOC.Cl
• Recent ClinicalTrials: Gemcitabine Hydrochloride With or Without Erlotinib Hydrochloride Followed by the Same Chemotherapy Regimen With or Without Radiation Therapy and Capecitabine or Fluorouracil in Treating Patients With Pancreatic Cancer That Has Been Removed by Surgery
• Recent EU Clinical Trials: The ROME trial from histology to target: the road to personalize target therapy and immunotherapy
• Recent NIPH Clinical Trials: A Phase I Study of ARQ 197 in Combination with Erlotinib
• Description: Erlotinib, launched as once daily oral treatment for patients with non-small-cell lung cancer (NSCLC), is an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, and it is the second small-molecule drug to be marketed with this mechanism of action. Both erlotinib and its predecessor, gefitinib, are members of the anilinoquinazoline class of tyrosine kinase inhibitors. They compete with the binding of ATP to the intracellular tyrosine kinase domain of EGFR, thereby inhibiting receptor autophosphorylation and blocking downstream signal transduction. Erlotinib is prepared by the condensation of 3-ethynylaniline with 4-chloro-6,7-bis(2-methoxyethoxy)quinazoline, which is a key intermediate obtained in five synthetic steps starting from ethyl 3,4- dihydroxybenzoate. In vitro, Erlotinib inhibits purified human EGFR tyrosine kinase with an IC50 of 2 nM and blocks EGFR autophosphorylation in cellular assays with an IC50 of 20nM. Treatment of human colon cancer cells with erlotinib was associated with growth inhibition, G1 cell cycle arrest, and apoptosis. Oral administration of erlotinib in athymic mice produced potent antitumor effects with an ED50 of 9.2 mg/kg/day for HN5 head and neck xenografts and 14 mg/ kg/day for A431 epidermoid xenografts. The absorption of Erlotinib following oral dosing is approximately 60%. Food greatly enhances the absorption allowing for almost 100% bioavailability of the dose. The time to reach peak plasma levels of the drug is about 4 hours, and the half-life is approximately 36 hours. Steady-state drug levels are reached in 7 to 8 days. Erlotinib has high protein binding (93%) and has an apparent volume of distribution of 232 L. It is metabolized primarily by CYP3A4 and to a lesser extent by CYP1A2 and CYP1A1. The drug is mainly excreted in the feces with less than 9% of the dose found in the urine. Erlotinib is labeled for the treatment of patients with locally advanced or metastatic NSCLC who have failed one or more previous chemotherapy regimens. The recommended dosage is 150 mg daily until disease progression is detected. In a randomized, double blind, placebo-controlled trial involving 731 patients, 150 mg/day oral dose of erlotinib resulted in a median overall survival of 6.7 months compared with 4.7 months in the placebo group (p＜0.001). Progression-free survival was 9.9 weeks and 7.9 weeks in the erlotinib and placebo groups, respectively (p＜0.001). Survival at one year was 31.2% in the erlotinib group versus 21.5% in the placebo group. The use of erlotinib showed greater benefit in patients with EGFR positive tumors and in those who never smoked. The most common adverse events reported in clinical trials were rash (9%) and diarrhea (6%). Elevations in liver function tests were also seen; however, these effects were mainly transient or associated with liver metastases. As previously noted for gefitinib, erlotinib is also shown to lack any clinical benefit in concurrent administration with platinum-based chemotherapy.
• Uses: Erlotinib hydrochloride (V), a quinazoline derived small molecule inhibitor of epidermal growth factor receptor (EDGFR) tyrosine kinase, was approved in November, 2004, for the treatment of advanced or metastatic non-smallcell lung cancer. It belongs to the same class as gefitinib,another quinazoline approved for treatment of advanced lung cancer, but with improved pharmacokinetic properties. The molecule was originated by Pfizer and development initiated in collaboration with OSI, which assumed full rights to the drug when Pfizer merged with Warner Lambert. Subsequently, Genentech/Roche went into licensing agreement with OSI to develop and market the drug in the US and Worldwide. Selective epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor. Antineoplastic Erlotinib HCl is an HER1/EGFR inhibitor with IC50 of 2 nM. Erlotinib HCl (OSI-744) is an EGFR inhibitor with IC50 of 2 nM, >1000-fold more sensitive for EGFR than human c-Src or v-Abl. Phase 3.

Technology Process of Erlotinib hydrochloride

There total 62 articles about Erlotinib hydrochloride 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%

erlotinib (183321-74-6) → erlotinib hydrochloride (183319-69-9)

Guidance literature:

With hydrogenchloride; In isopropyl alcohol; at 0 ℃; for 1h; Product distribution / selectivity; Inert atmosphere;

Reference yield: 100.0%

6,7-bis(2-methoxyethoxy)-4-methoxyquinazoline (1312937-41-9) + hydrochloric salt of m-aminophenylacetylene (207226-02-6) → erlotinib hydrochloride (183319-69-9)

Guidance literature:

hydrochloric salt of m-aminophenylacetylene; With sec.-butyllithium; In tetrahydrofuran; cyclohexane; at 0 ℃; for 0.5h; Inert atmosphere;

6,7-bis(2-methoxyethoxy)-4-methoxyquinazoline; In tetrahydrofuran; cyclohexane; at 20 ℃; for 15h;

With hydrogenchloride; In tetrahydrofuran; cyclohexane; water; at 20 ℃; for 1h; Product distribution / selectivity;

Reference yield: 98.0%

3-acetylenephenylamine (54060-30-9) + 4-chloro-6,7-bis(2-methoxyethoxy)quinazoline (183322-18-1) → erlotinib hydrochloride (183319-69-9)

Guidance literature:

In isopropyl alcohol; for 18h; Heating;

upstream raw materials:

3-acetylenephenylamine

4-chloro-6,7-bis(2-methoxyethoxy)quinazoline

erlotinib

4-(methylthio)-6,7-bis(2-methoxyethoxy)quinazoline

Downstream raw materials:

erlotinib

[6,7-bis(2-methoxyethoxy)-4-chinazolinyl](3-ethynylphenyl)amine adipinate

N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine, methanesulfonic acid salt

Refernces

• 1、 Chandregowda, Venkateshappa,Rao, Gudapati Venkateswara,Reddy, Goukanapalli Chandrasekara. "Improved synthesis of gefitinib and erlotinib hydrochloride- anticancer agents". . p. 3409 - 3415. Retrieved 2007.
• 2、 -. "Preparation method of erbtinib". Paragraph 0009; 0048-0053. . Retrieved 2020/06/16.
• 3、 -. "Preparation method for high-purity erlotinib hydrochloride". Paragraph 0040-0049. . Retrieved 2019/05/16.