GSK 525762A

Base Information

• Chemical Name: GSK 525762A
• CAS No.: 1260907-17-2
• Molecular Formula: C22H22ClN5O2
• Molecular Weight: 423.902
• Mol file: 1260907-17-2.mol

Synonyms:I-BET-762;GSK525762;Cibinetide;Molibresib;GSK 525762A;IBET762(GSK525762A);Molibresib (I-BET762;GSK525762 (I-BET-762);GSK 525762A USP/EP/BP;GSK 525762A (I-BET-762)

Chemical Property of GSK 525762A

Chemical Property:

• PKA: 15.71±0.46(Predicted)
• PSA: 84.89000
• Density: 1.35
• LogP: 3.93190
• Storage Temp.: 2-8°C
• Solubility.: Soluble in DMSO (up to at least 25 mg/ml) or in Ethanol (up to at least 25 mg/ml)

Purity/Quality:

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

GSK 525762A ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: The bromodomain and extra terminal domain (BET) family of proteins, including BRD2, BRD3, and BRD4, affect inflammatory gene expression by controlling the assembly of histone acetylation-dependent chromatin complexes. I-BET762 is a synthetic compound which interacts with BET proteins with high-affinity (Kd = 32.5-42.5 nM). It blocks binding of BET proteins with acetylated histones, disrupting the formation of chromatin complexes involved in the expression of specific inflammatory genes in activated macrophages. Through these actions, I-BET762 provides protection against bacteria-induced sepsis and lipopolysaccharide-triggered endotoxic shock.
• Uses: GSK 525762A, is a BET Bromodomain Inhibitor, which is now in clinical development. BET bromodomains have emerged as promising drug targets for treatment of cancers, inflammatory diseases, and other medical conditions.

Technology Process of GSK 525762A

There total 18 articles about GSK 525762A 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: 85.0%

methanol (67-56-1) + ethylamine (75-04-7,85404-22-4) → 2-[(4S)-6-(4-chlorophenyl)-1-methyl-8-(methyloxy)-4H-[1,2,4]triazolo[4,3-a][1,4] benzodiazepin-4-yl]-N-ethylacetamide (1260907-17-2)

Guidance literature:

With DIEA; HBTU; In tetrahydrofuran; 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran; acetonitrile;

Reference yield: 47.0%

[(4S)-6-(4-chlorophenyl)-1-methyl-8-(methyloxy)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]acetic acid (1300019-38-8) + ethylamine (75-04-7,85404-22-4) → 2-[(4S)-6-(4-chlorophenyl)-1-methyl-8-(methyloxy)-4H-[1,2,4]triazolo[4,3-a][1,4] benzodiazepin-4-yl]-N-ethylacetamide (1260907-17-2)

Guidance literature:

[(4S)-6-(4-chlorophenyl)-1-methyl-8-(methyloxy)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]acetic acid; With N-ethyl-N,N-diisopropylamine; HATU; In tetrahydrofuran; at 20 ℃; for 3h;

ethylamine; In tetrahydrofuran; for 48h;

Reference yield:

methyl N1-[2-[(4-chlorophenyl)carbonyl]-4-(methyloxy)phenyl]-N2-{[(9H-fluoren-9-ylmethyl)oxy]carbonyl}-L-α-asparaginate (1300019-48-0) → 2-[(4S)-6-(4-chlorophenyl)-1-methyl-8-(methyloxy)-4H-[1,2,4]triazolo[4,3-a][1,4] benzodiazepin-4-yl]-N-ethylacetamide (1260907-17-2)

Guidance literature:

Multi-step reaction with 8 steps

1.1: triethylamine / dichloromethane / 24 h / Reflux

2.1: acetic acid / 1,2-dichloro-ethane / 2 h / 60 °C

3.1: tetraphosphorus decasulfide; sodium carbonate / 1,2-dichloro-ethane / 2 h / 70 °C

4.1: hydrazine hydrate / tetrahydrofuran / 4 h / 0 - 15 °C

5.1: triethylamine / tetrahydrofuran / 1 h / 20 °C

6.1: acetic acid / tetrahydrofuran / 48 h / 20 °C

7.1: sodium hydroxide / tetrahydrofuran / 5 h / 20 °C

8.1: N-ethyl-N,N-diisopropylamine; HATU / tetrahydrofuran / 3 h / 20 °C

8.2: 48 h

With tetraphosphorus decasulfide; sodium carbonate; hydrazine hydrate; acetic acid; triethylamine; N-ethyl-N,N-diisopropylamine; HATU; sodium hydroxide; In tetrahydrofuran; dichloromethane; 1,2-dichloro-ethane;

upstream raw materials:

(4-chlorphenyl)magnesium bromide

[(4S)-6-(4-chlorophenyl)-1-methyl-8-(methyloxy)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]acetic acid

ethylamine

2-Amino-5-methoxybenzoic acid

Downstream raw materials:

2-[(4S)-6-(4-chlorophenyl)-1-methyl-8-(methyloxy)-4H-[1,2,4]triazolo[4,3-a][1,4] benzodiazepin-4-yl]-N-ethylacetamide benzene sulphonic acid salt

tert-butyl (17-(((4S)-6-(4-chlorophenyl)-4-(2-(ethylamino)-2-oxoethyl)-1-methyl-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepin-8-yl)oxy)-3,6,9,12,15-pentaoxaheptadecyl)carbamate

Refernces

• 1、 Erickson, Greg A.,Hatcher, Mark A.,Journet, Michel,Kowalski, John A.,Lovelace, Tom C.,Pink, Christopher J.,Xie, Shiping. "Preparation of Methyltriazolo[1,4]benzodiazepine via Oxidative Activation of a Thiolactam for the Synthesis of BET Inhibitor Molibresib". . . Retrieved 2021/05/29.
• 2、 -. "Benzodiazepine Bromodomain Inhibitor". . . Retrieved 2012/09/10.