(R)-6-(4-((4-Ethylpiperazin-1-yl)methyl)phenyl)-N-(1-phenylethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Base Information

• Chemical Name: (R)-6-(4-((4-Ethylpiperazin-1-yl)methyl)phenyl)-N-(1-phenylethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine
• CAS No.: 497839-62-0
• Molecular Formula: C27H32N6
• Molecular Weight: 440.591
• UNII: F9JLR95I3I
• DSSTox Substance ID: DTXSID90964400
• Nikkaji Number: J2.354.685J
• Wikipedia: AEE788
• Wikidata: Q4651286
• NCI Thesaurus Code: C48369
• Pharos Ligand ID: 3H6QX6ZASBWM
• Metabolomics Workbench ID: 153526
• ChEMBL ID: CHEMBL587723
• Mol file: 497839-62-0.mol

Synonyms:AEE 788;AEE-788;AEE788;NVP-AEE788

Chemical Property of (R)-6-(4-((4-Ethylpiperazin-1-yl)methyl)phenyl)-N-(1-phenylethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Chemical Property:

• Boiling Point: 639.246 °C at 760 mmHg
• Flash Point: 340.404 °C
• PSA: 63.31000
• Density: 1.204 g/cm³
• LogP: 4.23320
• Storage Temp.: -20°C
• Solubility.: ≥22.05 mg/mL in DMSO; insoluble in H2O; ≥14.4 mg/mL in EtOH with ultrasonic
• XLogP3: 4.6
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 7
• Exact Mass: 440.26884505
• Heavy Atom Count: 33
• Complexity: 579

Purity/Quality:

99% ^*data from raw suppliers

AEE 788 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CCN1CCN(CC1)CC2=CC=C(C=C2)C3=CC4=C(N3)N=CN=C4NC(C)C5=CC=CC=C5
• Isomeric SMILES: CCN1CCN(CC1)CC2=CC=C(C=C2)C3=CC4=C(N3)N=CN=C4N[C@H](C)C5=CC=CC=C5
• Recent ClinicalTrials: Study of AEE788 in Patients With Recurrent/Relapse Glioblastoma Multiforme (GBM)
• Description: AEE788 (NVP-AEE788) is a potent inhibitor of EGFR and HER2/ErbB2 with IC50 of 2 nM and 6 nM, less potent to VEGFR2/KDR, c-Abl, c-Src, and Flt-1, does not inhibit Ins-R, IGF-1R, PKCα and CDK1. Phase 1/2. AEE788 is an inhibitor of both epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) receptor tyrosine kinase family members. It can inhibit EGFR and VEGFR tyrosine kinases with IC50 values of 2, 6, 77, and 59 nM for EGFR, ErbB2, KDR, and FLT1, respectively. AEE788 demonstrates antiproliferative activity against a range of EGFR and ErbB2-overexpressing cell lines and can inhibit the proliferation of EGF- and VEGF-stimulated human umbilical vein endothelial cells. It also has been shown to have antitumor and anti-angiogenic activity in numerous animal models of cancer.
• Uses: AEE788 is a novel multitargeted human epidermal receptor (HER) 1/2 and vascular endothelial growth factor receptor (VEGFR) 1/2 receptor family tyrosine kinases inhibitor with IC50 of 2, 6, 77, 59 nM for EGFR, ErbB2, KDR, and Flt-1. A novel dual receptor tyrosine kinase inhibitor of the EGF and the VEGF receptor, for treatment of human HCC cell lines and in a s.c. xenograft model. AEE788 is an inhibitor of both epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) receptor tyrosine kinase family members. It can inhibit EGFR and VEGFR tyrosine kinases with IC50 values of 2, 6, 77, and 59 nM for EGFR, ErbB2, KDR, and FLT1, respectively. AEE788 demonstrates antiproliferative activity against a range of EGFR and ErbB2-overexpressing cell lines and can inhibit the proliferation of EGF- and VEGF-stimulated human umbilical vein endothelial cells. It also has been shown to have antitumor and anti-angiogenic activity in numerous animal models of cancer.[Cayman Chemical]

Technology Process of (R)-6-(4-((4-Ethylpiperazin-1-yl)methyl)phenyl)-N-(1-phenylethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine

There total 10 articles about (R)-6-(4-((4-Ethylpiperazin-1-yl)methyl)phenyl)-N-(1-phenylethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine 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:

(4-ethyl-piperazin-1-yl)-{4-[4-((R)-1-phenyl-ethylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-phenyl}-methanone (924637-25-2) → {6-[4-(4-ethylpiperazin-1-ylmethyl)-phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}-((R)-1-phenylethyl)amine (497839-62-0)

Guidance literature:

(4-ethyl-piperazin-1-yl)-{4-[4-((R)-1-phenyl-ethylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-phenyl}-methanone; With lithium aluminium tetrahydride; In tetrahydrofuran; at 25 - 50 ℃; for 3h;

With water; In tetrahydrofuran; for 2.5h; Product distribution / selectivity;

Reference yield:

4-ethylpiperazine (5308-25-8) + 4-[4-((R)-1-phenyl-ethylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-benzoic acid ethyl ester (497841-26-6) → {6-[4-(4-ethylpiperazin-1-ylmethyl)-phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}-((R)-1-phenylethyl)amine (497839-62-0)

Guidance literature:

4-ethylpiperazine; 4-[4-((R)-1-phenyl-ethylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-benzoic acid ethyl ester; With lithium aluminium tetrahydride; In tetrahydrofuran; at 25 - 50 ℃; for 3h;

With water; In tetrahydrofuran; for 2.5h;

With sodium hydroxide; sodium tetrahydroborate; water; acetic acid; more than 3 stages; Product distribution / selectivity;

Reference yield:

2,4-dichloro-6-iodo-7H-pyrrolo[2,3-d]pyrimidine → {6-[4-(4-ethylpiperazin-1-ylmethyl)-phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}-((R)-1-phenylethyl)amine (497839-62-0)

Guidance literature:

Multi-step reaction with 6 steps

1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate / 1,4-dioxane / 4 h / 100 °C

2: butan-1-ol / 3 h / 145 °C

3: lithium chloride / water; ethanol / 3 h / 55 °C

4: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 2 h

5: palladium on activated charcoal; hydrogen; triethylamine / ethanol

6: lithium aluminium tetrahydride / tetrahydrofuran / 2 h / 50 °C

With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; lithium aluminium tetrahydride; palladium on activated charcoal; hydrogen; potassium carbonate; triethylamine; 1,1'-carbonyldiimidazole; lithium chloride; In tetrahydrofuran; 1,4-dioxane; ethanol; water; N,N-dimethyl-formamide; butan-1-ol;

upstream raw materials:

4-ethylpiperazine

4-[4-((R)-1-phenyl-ethylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-benzoic acid ethyl ester

(4-ethyl-piperazin-1-yl)-{4-[4-((R)-1-phenyl-ethylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-phenyl}-methanone

Refernces

• 1、 -. "ORGANIC COMPOUNDS". Page/Page column 7-8. . Retrieved 2010/11/25.