GNE-0877

Base Information

• Chemical Name: GNE-0877
• CAS No.: 1374828-69-9
• Molecular Formula: C₁₄H₁₆F₃N₇
• Molecular Weight: 339.323
• Mol file: 1374828-69-9.mol

Synonyms:GNE-0877;alpha,alpha,3-Trimethyl-4-[[4-(methylamino)-5-(trifluoromethyl)-2-pyrimidinyl]amino]-1H-pyrazole-1-acetonitrile;2-methyl-2-(3-methyl-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-1H-pyrazol-1-yl)propanenitrile;alpha,alpha,3-Trimethyl-4-[[4-(methylamino)-5-(trifluoromethyl)-2-pyrimidinyl]amino]-1H-pyrazole-1-acetonitrile GNE-0877;GNE-0877, >=98%

Chemical Property of GNE-0877

Chemical Property:

• Boiling Point: 506.3±60.0 °C(Predicted)
• PKA: 3.87±0.10(Predicted)
• PSA: 91.45000
• Density: 1.36±0.1 g/cm3(Predicted)
• LogP: 3.19028
• Storage Temp.: -20°C, Inert atmosphere
• Solubility.: DMSO (Slightly), Methanol (Slightly)

Purity/Quality:

98% min ^*data from raw suppliers

GNE-0877 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: Leucine-rich repeat kinase 2 (LRRK2) is an enzyme that interacts with parkin, a ligase that is part of the ubiquitin-proteasome system that mediates the targeting of proteins for degradation. Loss of function of the parkin protein leads to dopaminergic cell death. The development of Parkinson''s disease has been strongly associated with mutations in the LRRK2 gene that lead to increased kinase activity. GNE 0877 is a selective, brain-penetrable LRRK2 inhibitor (Ki = 0.7 nM). It inhibits LRRK2 Ser1292 autophosphorylation in BAC transgenic mice expressing human LRRK2 protein with the G2019S Parkinson’s disease mutation with an IC50 value of 3 nM in vivo.
• Uses: GNE-0877 is a highly potent and selective leucine-rich repeat kinase 2 (LRRK2) inhibitor.

Technology Process of GNE-0877

There total 7 articles about GNE-0877 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: 67.0%

2-methyl-2-(3-methyl-4-((4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)propanamide (1374829-45-4) → 2-methyl-2-(3-methyl-4-((4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)propanenitrile (1374828-69-9)

Guidance literature:

With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; In ethyl acetate; at 75 ℃; for 17h; Large scale;

Reference yield:

2-methyl-2-(3-methyl-4-nitro-1H-pyrazol-1-yl)propanamide (1374829-43-2) → 2-methyl-2-(3-methyl-4-((4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)propanenitrile (1374828-69-9)

Guidance literature:

Multi-step reaction with 3 steps

1.1: hydrogen / palladium on activated charcoal / methanol / 1 h / 20 °C / 760.05 Torr / Inert atmosphere

2.1: trifluoroacetic acid / 2-methoxy-ethanol / 0.5 h / 70 °C

2.2: 20 °C / pH 8

3.1: trichlorophosphate / 1 h / 90 °C

3.2: pH 8 / Cooling with ice

With hydrogen; trifluoroacetic acid; trichlorophosphate; palladium on activated charcoal; In methanol; 2-methoxy-ethanol;

Reference yield:

2-methyl-2-(3-methyl-4-nitro-1H-pyrazol-1-yl)propanoic acid (1006435-72-8) → 2-methyl-2-(3-methyl-4-((4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)propanenitrile (1374828-69-9)

Guidance literature:

Multi-step reaction with 4 steps

1.1: oxalyl dichloride / dichloromethane / 2 h / 20 °C

1.2: 1 h / 20 °C

2.1: hydrogen / palladium on activated charcoal / methanol / 1 h / 20 °C / 760.05 Torr / Inert atmosphere

3.1: trifluoroacetic acid / 2-methoxy-ethanol / 0.5 h / 70 °C

3.2: 20 °C / pH 8

4.1: trichlorophosphate / 1 h / 90 °C

4.2: pH 8 / Cooling with ice

With oxalyl dichloride; hydrogen; trifluoroacetic acid; trichlorophosphate; palladium on activated charcoal; In methanol; dichloromethane; 2-methoxy-ethanol;

upstream raw materials:

5-bromo-2-chloro-N-methyl-pyrimidin-4-amine

2-methyl-2-(3-methyl-4-nitro-1H-pyrazol-1-yl)propanamide

2-methyl-2-(3-methyl-4-((4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)propanamide

2-methyl-2-(3-methyl-4-nitro-1H-pyrazol-1-yl)propanoic acid

Refernces

• 1、 Estrada, Anthony A.,Chan, Bryan K.,Baker-Glenn, Charles,Beresford, Alan,Burdick, Daniel J.,Chambers, Mark,Chen, Huifen,Dominguez, Sara L.,Dotson, Jennafer,Drummond, Jason,Flagella, Michael,Fuji, Reina,Gill, Andrew,Halladay, Jason,Harris, Seth F.,Heffron, Timothy P.,Kleinheinz, Tracy,Lee, Donna W.,Pichon, Claire E. Le,Liu, Xingrong,Lyssikatos, Joseph P.,Medhurst, Andrew D.,Moffat, John G.,Nash, Kevin,Scearce-Levie, Kimberly,Sheng, Zejuan,Shore, Daniel G.,Wong, Susan,Zhang, Shuo,Zhang, Xiaolin,Zhu, Haitao,Sweeney, Zachary K.. "Discovery of highly potent, selective, and brain-penetrant aminopyrazole Leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors". . p. 921 - 936. Retrieved 2014/03/21.