1-(5-(4-amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-4-fluoroindolin-1-yl)-2-(6-methylpyridin-2-yl)ethanone

Base Information

• Chemical Name: 1-(5-(4-amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-4-fluoroindolin-1-yl)-2-(6-methylpyridin-2-yl)ethanone
• CAS No.: 1337532-29-2
• Molecular Formula: C23H21FN6O
• Molecular Weight: 416.4508432
• DSSTox Substance ID: DTXSID101103941
• Pharos Ligand ID: VTAUDF2333N2
• ChEMBL ID: CHEMBL2441340
• Mol file: 1337532-29-2.mol

Synonyms:GSK2656157

Chemical Property of 1-(5-(4-amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-4-fluoroindolin-1-yl)-2-(6-methylpyridin-2-yl)ethanone

Chemical Property:

• Appearance/Colour: Light yellow to khaki solid
• Boiling Point: 744.6±60.0 °C(Predicted)
• PKA: 5.32±0.30(Predicted)
• PSA: 89.93000
• Density: 1.43±0.1 g/cm3(Predicted)
• LogP: 3.83800
• Storage Temp.: -20°C
• Solubility.: Soluble in DMSO (10 mg/ml with warming)
• XLogP3: 2.3
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 3
• Exact Mass: 416.17608748
• Heavy Atom Count: 31
• Complexity: 666

Purity/Quality:

99%+, ^*data from raw suppliers

GSK2656157 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1=NC(=CC=C1)CC(=O)N2CCC3=C2C=CC(=C3F)C4=CN(C5=NC=NC(=C45)N)C
• Description: GSK2656157 (1337532-29-2) is a potent (IC50 = 0.9 nM) and selective (over 300 kinases) inhibitor of protein kinase RNA-like endoplasmic reticulum kinase (PERK).1,2? Inhibited growth of multiple human tumor xenografts in mice. GSK2656157 has also been found to potently inhibit RIPK1 (IC50 = 69 nM) and TNF-mediated RIPK1 kinase-dependent cell death in mouse embryonic fibroblasts.3 It prevented the loss of dendritic spines and rescued memory deficits after traumatic brain injury.4? GSK2656157 also enhanced glucose-stimulated insulin secretion in a mouse model of type 2 diabetes mellitus.5
• Uses: GSK2656157 is an ATP-competitive and highly selective inhibitor of PKR-like endoplasmic reticulum kinase (PERK) enzyme activity. GSK2656157 also has anti-tumor and anti-angiogenic activity.

Technology Process of 1-(5-(4-amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-4-fluoroindolin-1-yl)-2-(6-methylpyridin-2-yl)ethanone

There total 10 articles about 1-(5-(4-amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-4-fluoroindolin-1-yl)-2-(6-methylpyridin-2-yl)ethanone 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%

(6-methyl-2-pyridinyl)acetic acid trifluoroacetic acid + (4-fluoro-2,3-dihydro-1H-indol-5-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine dihydrochloride → GSK2656157 (1337532-29-2)

Guidance literature:

(4-fluoro-2,3-dihydro-1H-indol-5-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine dihydrochloride; With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 0 - 20 ℃; for 0.166667h;

(6-methyl-2-pyridinyl)acetic acid trifluoroacetic acid; at 5 - 20 ℃; for 3h;

DOI:10.1021/ml400228e

Reference yield:

2,3-dihydro-4-fluoro-1H-indole (552866-98-5) → GSK2656157 (1337532-29-2)

Guidance literature:

Multi-step reaction with 6 steps

1.1: dmap; N-ethyl-N,N-diisopropylamine / chloroform / 96 h

2.1: N-Bromosuccinimide / dichloromethane / 2 h / 20 °C

3.1: potassium acetate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / 1,4-dioxane / 80 °C / Inert atmosphere

4.1: tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; potassium phosphate; tri-tert-butylphosphonium tetrafluoroborate / 1,4-dioxane; water / 2 h / 20 - 80 °C / Inert atmosphere

5.1: hydrogenchloride / 1,4-dioxane / 20 °C

6.1: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 0.17 h / 0 - 20 °C

6.2: 3 h / 5 - 20 °C

With hydrogenchloride; dmap; potassium phosphate; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; N-Bromosuccinimide; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; tri-tert-butylphosphonium tetrafluoroborate; potassium acetate; N-ethyl-N,N-diisopropylamine; HATU; In 1,4-dioxane; dichloromethane; chloroform; water; N,N-dimethyl-formamide;

DOI:10.1021/ml400228e

Reference yield:

4-fluoroindole (387-43-9) → GSK2656157 (1337532-29-2)

Guidance literature:

Multi-step reaction with 7 steps

1.1: sodium cyanoborohydride / acetic acid / 1 h / 20 °C / Cooling with ice

2.1: dmap; N-ethyl-N,N-diisopropylamine / chloroform / 96 h

3.1: N-Bromosuccinimide / dichloromethane / 2 h / 20 °C

4.1: potassium acetate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / 1,4-dioxane / 80 °C / Inert atmosphere

5.1: tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; potassium phosphate; tri-tert-butylphosphonium tetrafluoroborate / 1,4-dioxane; water / 2 h / 20 - 80 °C / Inert atmosphere

6.1: hydrogenchloride / 1,4-dioxane / 20 °C

7.1: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 0.17 h / 0 - 20 °C

7.2: 3 h / 5 - 20 °C

With hydrogenchloride; dmap; potassium phosphate; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; N-Bromosuccinimide; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; tri-tert-butylphosphonium tetrafluoroborate; potassium acetate; sodium cyanoborohydride; N-ethyl-N,N-diisopropylamine; HATU; In 1,4-dioxane; dichloromethane; chloroform; water; acetic acid; N,N-dimethyl-formamide;

DOI:10.1021/ml400228e

upstream raw materials:

2,3-dihydro-4-fluoro-1H-indole

4-fluoroindole

1,1-dimethylethyl 4-fluoro-2,3-dihydro-1H-indole-1-carboxylate

1,1-dimethylethyl 5-(4-amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-4-fluoro-2,3-dihydro-1H-indole-1-carboxylate

Refernces

• 1、 Axten, Jeffrey M.,Romeril, Stuart P.,Shu, Arthur,Ralph, Jeffrey,Medina, Jesus R.,Feng, Yanhong,Li, William Hoi Hong,Grant, Seth W.,Heerding, Dirk A.,Minthorn, Elisabeth,Mencken, Thomas,Gaul, Nathan,Goetz, Aaron,Stanley, Thomas,Hassell, Annie M.,Gampe, Robert T.,Atkins, Charity,Kumar, Rakesh. "Discovery of GSK2656157: An optimized PERK inhibitor selected for preclinical development". . p. 964 - 968. Retrieved 2013/10/22.