MLN-8237

Base Information

• Chemical Name: MLN-8237
• CAS No.: 1028486-01-2
• Molecular Formula: C27H20ClFN4O4
• Molecular Weight: 518.932
• Mol file: 1028486-01-2.mol

Synonyms:Alisertib

Chemical Property of MLN-8237

Chemical Property:

• Boiling Point: 729.134 °C at 760 mmHg
• PKA: 4.07±0.10(Predicted)
• Flash Point: 394.766 °C
• Density: 1.438 g/cm³
• Storage Temp.: -20°C
• Solubility.: Soluble in DMSO (up to 5 mg/ml)

Purity/Quality:

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

MLN 8237 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: Alisertib (MLN8237) is a selective Aurora A inhibitor with IC50 of 1.2 nM in a cell-free assay. It has >200-fold higher selectivity for Aurora A than Aurora B. Phase 3. Alisertib (MLN8237, 1028486-01-2) is a highly selective and potent (IC50?= 1 nM) cell permeable inhibitor of Aurora A with off-target binding at GABAA?(IC50?= 490 nM).1?It disrupts the Aurora A-Myc complex leading to Myc degradation2?in Myc amplified neuroblastomas3?and p53-mutant human hepatocellular carcinoma cell4. Alisertib has been found to induce apoptosis and autophagy in breast cancer5?and melanoma6?cells?via?suppression of activation of the p38 MAPK pathway.
• Uses: An Aurora kinase inhibitor, used to treat patients with advanced solid tumors.

Technology Process of MLN-8237

There total 10 articles about MLN-8237 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: 80.0%

4-{[amino(imino)methyl]amino}-2-methoxybenzoic acid hydrochloride (1028486-08-9) + 8-chloro-4-[(dimethylamino)methylene]-1-(2-fluoro-6-methoxyphenyl)-3,4-dihydro-5H-2-benzazepin-5-one (869367-33-9) → alisertib (1028486-01-2)

Guidance literature:

4-{[amino(imino)methyl]amino}-2-methoxybenzoic acid hydrochloride; 8-chloro-4-[(dimethylamino)methylene]-1-(2-fluoro-6-methoxyphenyl)-3,4-dihydro-5H-2-benzazepin-5-one; With potassium carbonate; In methanol; at 50 - 55 ℃; for 24h;

With hydrogenchloride; In methanol; water; at 20 - 55 ℃; for 2h; pH=3;

Reference yield:

4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoic acid ammonium salt (1028486-10-3) → alisertib (1028486-01-2)

Guidance literature:

With hydrogenchloride; water; for 0.5h; pH=1;

Reference yield:

(5-chloro-2-iodophenyl)(2,6-difluorophenyl)methanone (869365-97-9) → alisertib (1028486-01-2)

Guidance literature:

Multi-step reaction with 4 steps

1.1: tert-butyl methyl ether; methanol / 3.5 h / 25 - 30 °C

2.1: diethylamine; copper(l) iodide / bis-triphenylphosphine-palladium(II) chloride / cyclohexane / 15 h / 28 - 33 °C / Inert atmosphere

3.1: trifluoroacetic acid / dichloromethane; water / 20 h / 20 - 35 °C

3.2: 2.5 h / 20 - 30 °C / pH 8

3.3: 20.5 h / 20 - 42 °C

4.1: potassium carbonate / methanol / 24 h / 50 - 55 °C

4.2: 2 h / 20 - 55 °C / pH 3

With copper(l) iodide; potassium carbonate; diethylamine; trifluoroacetic acid; bis-triphenylphosphine-palladium(II) chloride; In methanol; dichloromethane; tert-butyl methyl ether; cyclohexane; water;

upstream raw materials:

4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoic acid ammonium salt

Methyl 4-amino-2-methoxybenzoate

(5-chloro-2-iodophenyl)(2,6-difluorophenyl)methanone

(2-amino-5-chlorophenyl)-(2,6-difluorophenyl)methanone

Downstream raw materials:

4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoate sodium salt

Refernces

• 1、 -. "CRYSTALLINE FORMS OF SODIUM 4-{[9-CHLORO-7-(2-FLUORO-6--METHOXYPHENYL)-5H -PYRIMIDO[5,4-D][2]BENZAZEPIN-2YL]AMINO}-2-METHOXYBENZOATE". . . Retrieved 2011/09/19.