2-Methoxy-N-[(2E)-3-[4-[[3-methyl-4-[(6-methyl-3-pyridinyl)oxy]phenyl]amino]-6-quinazolinyl]-2-propen-1-yl]acetamide

Base Information

• Chemical Name: 2-Methoxy-N-[(2E)-3-[4-[[3-methyl-4-[(6-methyl-3-pyridinyl)oxy]phenyl]amino]-6-quinazolinyl]-2-propen-1-yl]acetamide
• CAS No.: 383432-38-0
• Molecular Formula: C27H27N5O3
• Molecular Weight: 469.543
• UNII: I05QZ0S4V3
• DSSTox Substance ID: DTXSID401026009
• Wikidata: Q27076902
• NCI Thesaurus Code: C26648
• Pharos Ligand ID: 2HQDUSSY1GJP
• Metabolomics Workbench ID: 153316
• ChEMBL ID: CHEMBL483321
• Mol file: 383432-38-0.mol

Synonyms:2-methoxy-N-(3-(4-((3-methyl-4-((6-methyl-3-pyridinyl)oxy)phenyl)amino)-6-quinazolinyl)-2-propenyl)acetamide;CP 724,714;CP 724714;CP-724,714;CP-724714;CP724,714;CP724714

Chemical Property of 2-Methoxy-N-[(2E)-3-[4-[[3-methyl-4-[(6-methyl-3-pyridinyl)oxy]phenyl]amino]-6-quinazolinyl]-2-propen-1-yl]acetamide

Chemical Property:

• Boiling Point: 687.304 °C at 760 mmHg
• PKA: 13.95±0.46(Predicted)
• Flash Point: 369.468 °C
• PSA: 98.26000
• Density: 1.251 g/cm³
• LogP: 5.41720
• XLogP3: 4.3
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 9
• Exact Mass: 469.21138974
• Heavy Atom Count: 35
• Complexity: 692

Purity/Quality:

98%min ^*data from raw suppliers

CP724714 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1=NC=C(C=C1)OC2=C(C=C(C=C2)NC3=NC=NC4=C3C=C(C=C4)C=CCNC(=O)COC)C
• Isomeric SMILES: CC1=NC=C(C=C1)OC2=C(C=C(C=C2)NC3=NC=NC4=C3C=C(C=C4)/C=C/CNC(=O)COC)C
• Recent ClinicalTrials: CP-724,714 in Treating Patients With Metastatic Breast Cancer
• Description: CP 724,714 is a selective inhibitor of HER2/ErbB2 with an IC50 value of 10 nM. It demonstrates greater than 640-fold selectivity against EGFR, InsR, IRG-1R, PDGFR, VEGFR2, Abl, Src, and c-Met. CP 724,714 has been shown to inhibit the proliferation of ErbB2-amplified cells, including BT474 and SK-BR-3 with IC50 values of 0.25 and 0.95 μM, respectively. It also demonstrates antitumor activity in various human tumor xenograft models. However, CP 724,714 was discontinued from clinical development due to hepatotoxicity caused by its ability to inhibit hepatic efflux transporters at low micromolar concentrations.
• Uses: CP 724714 is a HER-2 tyrosine kinase inhibitor used in tumor treatments for HER2 positive solid tumors.

Technology Process of 2-Methoxy-N-[(2E)-3-[4-[[3-methyl-4-[(6-methyl-3-pyridinyl)oxy]phenyl]amino]-6-quinazolinyl]-2-propen-1-yl]acetamide

There total 24 articles about 2-Methoxy-N-[(2E)-3-[4-[[3-methyl-4-[(6-methyl-3-pyridinyl)oxy]phenyl]amino]-6-quinazolinyl]-2-propen-1-yl]acetamide 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%

6-iodo-N-(3-methyl-4-((6-methylpyridin-3-yl)oxy)phenyl)quinazolin-4-amine (537705-05-8) + N-allyl-2-methoxyacetamide (486393-59-3) → (E)-2-methoxy-N-(3-{4-[3-methyl-4-(6-methylpyridin-3-yloxy)phenylamino]quinazolin-6-yl}allyl)acetamide (383432-38-0,537705-08-1)

Guidance literature:

With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; sodium acetate; triethylamine; In ethanol; for 6h; Reflux;

DOI:10.1021/op7000172

Reference yield: 90.0%

[6-(3-amino-propenyl)-quinazolin-4-yl]-[3-methyl-4-(6-methyl-pyridin-3-yloxy)-phenyl]-amine bishydrochloride + Methoxyacetyl chloride (38870-89-2) → (E)-2-methoxy-N-(3-{4-[3-methyl-4-(6-methylpyridin-3-yloxy)phenylamino]quinazolin-6-yl}allyl)acetamide (383432-38-0,537705-08-1)

Guidance literature:

With sodium hydroxide; In 2-methyltetrahydrofuran; water; for 1h;

Reference yield: 80.0%

Methoxyacetyl chloride (38870-89-2) + [6-(3-aminopropenyl)quinazolin-4-yl]-[3-methyl-4-(6-methylpyridin-3-yloxy)phenyl]amine dihydrochloride → (E)-2-methoxy-N-(3-{4-[3-methyl-4-(6-methylpyridin-3-yloxy)phenylamino]quinazolin-6-yl}allyl)acetamide (383432-38-0,537705-08-1)

Guidance literature:

[6-(3-aminopropenyl)quinazolin-4-yl]-[3-methyl-4-(6-methylpyridin-3-yloxy)phenyl]amine dihydrochloride; With sodium hydroxide; In 2-methyltetrahydrofuran; water; for 1h; Large scale;

Methoxyacetyl chloride; In 2-methyltetrahydrofuran; water; at 25 ℃; for 1h; Large scale;

DOI:10.1021/op050039u

upstream raw materials:

Methoxyacetyl chloride

6-iodo-N-(3-methyl-4-((6-methylpyridin-3-yl)oxy)phenyl)quinazolin-4-amine

N-propargyl-2-methoxyacetamide

5-Hydroxy-2-methylpyridine

Downstream raw materials:

E-2-methoxy-N-(3-{4-[3-methyl-4-(6-methyl-pyridin-3-yloxy)-phenylamino]-quinazolin-6-yl}-allyl)-acetamide monofumarate

E-2-methoxy-N-(3-{4-[3-methyl-4-(6-methyl-pyridin-3-yloxy)-phenylamino]-quinazolin-6-yl}-allyl)-acetamide monobesylate

Refernces

• 1、 -. "COMBINATIONS OF ERBB2 INHIBITORS WITH OTHER THERAPEUTIC AGENTS IN THE TREATMENT OF CANCER". Page/Page column 38; 49. . Retrieved 2008/06/13.
• 2、 Ripin, David H. Brown,Bourassa, Dennis E.,Brandt, Thomas,Castaldi, Michael J.,Frost, Heather N.,Hawkins, Joel,Johnson, Phillip J.,Massett, Stephen S.,Neumann, Karin,Phillips, James,Raggon, Jeffery W.,Rose, Peter R.,Rutherford, Jennifer L.,Sitter, Barbara,Stewart III, A. Morgan,Vetelino, Michael G.,Wei, Lulin. "Evaluation of kilogram-scale Sonagashira, Suzuki, and Heck coupling routes to oncology candidate CP-724,714". . p. 440 - 450. Retrieved 2012/12/25.