4-[[9-Chloro-7-(2,6-difluorophenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid

Base Information

• Chemical Name: 4-[[9-Chloro-7-(2,6-difluorophenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid
• CAS No.: 869363-13-3
• Molecular Formula: C25H15ClF2N4O2
• Molecular Weight: 476.87
• UNII: BX854EHD63
• ChEMBL ID: CHEMBL259084
• DSSTox Substance ID: DTXSID10235987
• Metabolomics Workbench ID: 153932
• NCI Thesaurus Code: C61075
• Nikkaji Number: J2.725.787I
• Pharos Ligand ID: ZYFSC9JV5SYD
• Wikidata: Q27087283
• Mol file: 869363-13-3.mol

Synonyms:4-((9-chloro-7-(2,6-difluorophenyl)-5H-pyrimidol(5,4-d)(2)benzazepin-2-yl)amino)benzoic acid;MLN8054

Chemical Property of 4-[[9-Chloro-7-(2,6-difluorophenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid

Chemical Property:

• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.696
• Boiling Point: 694.93°C at 760 mmHg
• PKA: 4.18±0.10(Predicted)
• Flash Point: 374.08°C
• PSA: 64.63000
• Density: 1.48
• LogP: 1.89720
• Solubility.: insoluble in EtOH; insoluble in H2O; ≥39.05 mg/mL in DMSO
• XLogP3: 5.2
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 4
• Exact Mass: 476.0851598
• Heavy Atom Count: 34
• Complexity: 755

Purity/Quality:

98%,99%, ^*data from raw suppliers

MLN 8054 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1C2=CN=C(N=C2C3=C(C=C(C=C3)Cl)C(=N1)C4=C(C=CC=C4F)F)NC5=CC=C(C=C5)C(=O)O
• Recent ClinicalTrials: A Phase 1 Trial of Extended MLN8054 Dosing in Patients With Advanced Malignancies
• Uses: MLN 8054 is an Aurora kinase inhibitor, used to treat patients with advanced solid tumors.

Technology Process of 4-[[9-Chloro-7-(2,6-difluorophenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid

There total 9 articles about 4-[[9-Chloro-7-(2,6-difluorophenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid 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: 56.0%

(E)-8-chloro-1-(2,6-difluorophenyl)-4-((dimethylamino)methylene)-3H-benzo[c]azepin-5(4H)-one + 4-guanidinobenzoic acid hydrochloride (42823-46-1) → 4-{[9-chloro-7-(2,6-difluorophenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}benzoic acid (869363-13-3)

Guidance literature:

With potassium carbonate; In ethanol; for 14h; Inert atmosphere; Reflux;

DOI:10.1002/anie.201200994

Reference yield: 45.0%

8-chloro-4-[(dimethylamino)methylene]-1-(2,6-difluorophenyl)-3,4-dihydro-5H-2-benzazepin-5-one (869366-10-9) + 4-guanidinobenzoic acid hydrochloride (42823-46-1) → 4-{[9-chloro-7-(2,6-difluorophenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}benzoic acid (869363-13-3)

Guidance literature:

With potassium carbonate sesquihydrate; In methanol; at 55 ℃; for 16h; Inert atmosphere;

DOI:10.1021/ml500409n

Reference yield:

tert-butyl (3-(4-chloro-2-(2,6-difluorobenzoyl)phenyl)prop-2-yn-1-yl)carbamate (869366-03-0) → 4-{[9-chloro-7-(2,6-difluorophenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}benzoic acid (869363-13-3)

Guidance literature:

Multi-step reaction with 3 steps

1: sulfuric acid / dichloromethane / 0 °C / Inert atmosphere

2: toluene / 4 h / 80 °C / Inert atmosphere

3: potassium carbonate / ethanol / 14 h / Inert atmosphere; Reflux

With sulfuric acid; potassium carbonate; In ethanol; dichloromethane; toluene;

DOI:10.1002/anie.201200994

upstream raw materials:

4-guanidinobenzoic acid hydrochloride

tert-butyl (3-(4-chloro-2-(2,6-difluorobenzoyl)phenyl)prop-2-yn-1-yl)carbamate

8-chloro-1-(2,6-difluorophenyl)-3,4-dihydrobenzo[c]azepin-5-one

tert-butyl (4-chloro-2-(2,6-difluorobenzoyl)phenyl)carbamate

Downstream raw materials:

N-(2-(4-aminopiperidin-1-yl)ethyl)-4-((9-chloro-7-(2,6-difluorophenyl)-5H-benzo[c]pyrimido[4,5-e]azepin-2-yl)amino)benzamide

tert-butyl (1-(2-(4-((9-chloro-7-(2,6-difluorophenyl)-5H-benzo[c]pyrimido[4,5-e]azepin-2-yl)amino)benzamido)ethyl)piperidin-4-yl)carbamate

Refernces

• 1、 Yang, Katherine S.,Budin, Ghyslain,Reiner, Thomas,Vinegoni, Claudio,Weissleder, Ralph. "Bioorthogonal imaging of Aurora Kinase A in live cells". supporting information; experimental part. p. 6598 - 6603. Retrieved 2012/09/22.