GSK1324726A (I-BET726)

Base Information

• Chemical Name: GSK1324726A (I-BET726)
• CAS No.: 1300031-52-0
• Molecular Formula: C25H23ClN2O3
• Molecular Weight: 434.922
• Mol file: 1300031-52-0.mol

Synonyms:GSK1324726A;4-[(2S,4R)-1-Acetyl-4-[(4-chlorophenyl)amino]-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl]benzoic acid;GSK1324726A (I-BET726);4-((2S,4R)-1-acetyl-4-(4-chlorophenylamino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoic acid

Chemical Property of GSK1324726A (I-BET726)

Chemical Property:

• Boiling Point: 707.3±60.0 °C(Predicted)
• PKA: 4.20±0.10(Predicted)
• PSA: 69.64000
• Density: 1.304±0.06 g/cm3(Predicted)
• LogP: 6.14150
• Solubility.: insoluble in H2O; ≥1.87 mg/mL in EtOH with gentle warming and ultrasonic; ≥17.7 mg/mL in DMSO

Purity/Quality:

95-99% ^*data from raw suppliers

GSK1324726A(I-BET726) >98% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: I-BET726 is an inhibitor of BET family proteins that binds BRD2, BRD3, and BRD4 with high affinity (IC50s = 41, 31, and 22 nM, respectively) and competes with tetra-acetylated histone 4 peptides for binding to the bromodomains of these proteins. It exhibits >1,000-fold selectivity for these proteins over other bromodomain-containing homologs. I-BET726 inhibits cell growth and induces cytotoxicity in neuroblastoma cell lines by modulating the expression of genes involved in apoptosis and Myc signaling. I-BET726 can be administered orally to animals, and it reduces tumor growth in mouse xenograft models of human neuroblastoma.

Technology Process of GSK1324726A (I-BET726)

There total 22 articles about GSK1324726A (I-BET726) 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: 87.0%

ethyl 4-{(2S,4R)-1-acetyl-4-[(4-chlorophenyl)amino]-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl}benzoate (1300694-19-2) → 4-((2S,4R)-1-acetyl-4-((4-chlorophenyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoic acid (1300031-52-0)

Guidance literature:

ethyl 4-{(2S,4R)-1-acetyl-4-[(4-chlorophenyl)amino]-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl}benzoate; With water; sodium hydroxide; In ethanol; at 20 ℃; for 2h;

With hydrogenchloride; In dichloromethane; water; pH=1;

Reference yield:

methyl 4-{(2S,4R)-1-acetyl-4-[(4-chlorophenyl)amino]-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl}benzoate (1300031-70-2) → 4-((2S,4R)-1-acetyl-4-((4-chlorophenyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoic acid (1300031-52-0)

Guidance literature:

methyl 4-{(2S,4R)-1-acetyl-4-[(4-chlorophenyl)amino]-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl}benzoate; With water; sodium hydroxide; In ethanol; for 1h; Reflux;

With hydrogenchloride; In water; pH=3;

Reference yield:

1-methylethyl [(2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (1300031-98-4) → 4-((2S,4R)-1-acetyl-4-((4-chlorophenyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoic acid (1300031-52-0)

Guidance literature:

Multi-step reaction with 4 steps

1.1: sodium carbonate / tetrakis(triphenylphosphine) palladium⁽⁰⁾ / 1,2-dimethoxyethane; water / 6 h / 105 °C / Inert atmosphere

2.1: aluminum (III) chloride / dichloromethane / 0.33 h / 0 - 6 °C

2.2: 0.51 h / 0 °C

3.1: sodium t-butanolate / DavePhos; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾ / toluene / 16 h / 70 °C / Inert atmosphere

4.1: sodium hydroxide; water / ethanol / 2 h / 20 °C

With aluminum (III) chloride; water; sodium carbonate; sodium hydroxide; sodium t-butanolate; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; tetrakis(triphenylphosphine) palladium⁽⁰⁾; DavePhos; In 1,2-dimethoxyethane; ethanol; dichloromethane; water; toluene;

upstream raw materials:

4-bromo-aniline

bromobenzene

bromochlorobenzene

(S)-3-(N-phenylamino)-butyronitrile

Downstream raw materials:

4-{(2S,4R)-1-acetyl-4-[(4-chlorophenyl)amino]-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl}benzamide

methyl 4-{(2S,4R)-1-acetyl-4-[(4-chlorophenyl)amino]-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl}benzoate

(2S,4R)-1-((S)-1-(4-((2S,4R)-1-acetyl-4-((4-chlorophenyl)-amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)phenyl)-15-(tert-butyl)-1,13-dioxo-5,8,11-trioxa-2,14-diazahexadecan-16-oyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide

4-((2S,4R)-1-acetyl-2-methyl-4-(phenylamino)-1,2,3,4-tetrahydroquinolin-6-yl)benzoic acid

Refernces

• 1、 -. "Tetrahydroquinoline Derivatives Useful As Bromodomain Inhibitors". . . Retrieved 2014/02/16.
• 2、 -. "TETRAHYDROQUINOLINE DERIVATIVES USEFUL AS BROMODOMAIN INHIBITORS". . . Retrieved 2012/11/07.