BI 882370

Base Information

• Chemical Name: BI 882370
• CAS No.: 1392429-79-6
• Molecular Formula: C₂₈H₃₃F₂N₇O₂S
• Molecular Weight: 569.679
• Mol file: 1392429-79-6.mol

Synonyms:N-(3-(5-((1-ethylpiperidin-4-yl)(methyl)amino)-3-(pyrimidin-5-yl)-1H-pyrrolo[3,2-b]pyridin- 1-yl)-2,4-difluorophenyl)propane-1-sulfonamide

Chemical Property of BI 882370

Chemical Property:

• Boiling Point: 649.6±65.0 °C(Predicted)
• PKA: 5.48±0.10(Predicted)
• Density: 1.37±0.1 g/cm3(Predicted)

Purity/Quality:

99%+, ^*data from raw suppliers

BI882370 >98% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

Useful:

• Description: BI-882370 is an orally bioavailable RAF inhibitor with IC50 values of 0.8, 0.8, and 0.6 nM for B-RAFV600E, wild-type B-RAF, and C-RAF in the DFG-out inactive conformation, respectively. It is selective for RAF over a panel of kinases, including LCK, KIT, Src, LYNA, LYNB, and PDGFR (IC50s = 49, 415, 485, 750, 715, and 1,220 nM, respectively). It inhibits proliferation of human B-RAF-mutant melanoma cells when used at concentrations ranging from 1 to 10 nM. It reduces tumor growth in multiple B-RAF-mutant melanoma and colorectal carcinoma mouse xenograft models when administered at a dose of 25 mg/kg twice per day. BI-882370, alone and in combination with trametinib , induces tumor regression in an A375 melanoma mouse xenograft model with no resistance developing within three or five weeks, respectively.

Technology Process of BI 882370

There total 10 articles about BI 882370 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: 100.0%

N-(2,4-difluoro-3-(5-(methyl(piperidin-4-yl)amino)-3-(pyrimidin-5-yl)-1H- pyrrolo[3,2-b]pyridin-1-yl)phenyl)propane-1-sulfonamide (1392429-51-4) + acetaldehyde (75-07-0,9002-91-9) → N-(3-(5-((1-ethylpiperidin-4-yl)(methyl)amino)-3-(pyrimidin-5-yl)-1H-pyrrolo[3,2-b]pyridin- 1-yl)-2,4-difluorophenyl)propane-1-sulfonamide (1392429-79-6)

Guidance literature:

N-(2,4-difluoro-3-(5-(methyl(piperidin-4-yl)amino)-3-(pyrimidin-5-yl)-1H- pyrrolo[3,2-b]pyridin-1-yl)phenyl)propane-1-sulfonamide; With sodium tris(acetoxy)borohydride; In dichloromethane; at 0 - 10 ℃; for 1h; Inert atmosphere; Large scale;

acetaldehyde; In dichloromethane; at 0 - 10 ℃; Inert atmosphere; Large scale;

With ammonium hydroxide; In dichloromethane; for 0.5h; Solvent; Large scale;

Reference yield:

N-(3-amino-2,6-difluorophenyl)acetamide (946826-47-7) → N-(3-(5-((1-ethylpiperidin-4-yl)(methyl)amino)-3-(pyrimidin-5-yl)-1H-pyrrolo[3,2-b]pyridin- 1-yl)-2,4-difluorophenyl)propane-1-sulfonamide (1392429-79-6)

Guidance literature:

Multi-step reaction with 8 steps

1.1: pyridine / dichloromethane / 16 h / 20 °C

2.1: hydrogenchloride / ethanol; water / 2 h / 80 °C

3.1: trifluoroacetic acid; sodium nitrite / 0.5 h / 0 °C

3.2: 0.25 h

4.1: copper(l) iodide; caesium carbonate; trans-N,N'-dimethylcyclohexane-1,2-diamine / toluene / 40 h / 120 °C / Inert atmosphere

5.1: N-iodo-succinimide / N,N-dimethyl-formamide; tetrahydrofuran / 1 h / 20 °C

6.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; lithium chloride; sodium carbonate / water; 1,4-dioxane / 1 h / 100 °C / Inert atmosphere

7.1: hydrogenchloride / methanol; dichloromethane; 1,4-dioxane / 3 h / 20 °C

8.1: sodium tris(acetoxy)borohydride / dichloromethane / 1 h / 0 - 10 °C / Inert atmosphere; Large scale

8.2: 0 - 10 °C / Inert atmosphere; Large scale

8.3: 0.5 h / Large scale

With pyridine; hydrogenchloride; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; N-iodo-succinimide; copper(l) iodide; sodium tris(acetoxy)borohydride; sodium carbonate; caesium carbonate; trans-N,N'-dimethylcyclohexane-1,2-diamine; trifluoroacetic acid; lithium chloride; sodium nitrite; In tetrahydrofuran; 1,4-dioxane; methanol; ethanol; dichloromethane; water; N,N-dimethyl-formamide; toluene;

Reference yield:

N-(2,6-difluoro-3-nitrophenyl)acetamide (25892-08-4) → N-(3-(5-((1-ethylpiperidin-4-yl)(methyl)amino)-3-(pyrimidin-5-yl)-1H-pyrrolo[3,2-b]pyridin- 1-yl)-2,4-difluorophenyl)propane-1-sulfonamide (1392429-79-6)

Guidance literature:

Multi-step reaction with 9 steps

1.1: hydrogen; palladium 10% on activated carbon / methanol / 3 h / 10343.2 Torr / Autoclave

2.1: pyridine / dichloromethane / 16 h / 20 °C

3.1: hydrogenchloride / ethanol; water / 2 h / 80 °C

4.1: trifluoroacetic acid; sodium nitrite / 0.5 h / 0 °C

4.2: 0.25 h

5.1: copper(l) iodide; caesium carbonate; trans-N,N'-dimethylcyclohexane-1,2-diamine / toluene / 40 h / 120 °C / Inert atmosphere

6.1: N-iodo-succinimide / N,N-dimethyl-formamide; tetrahydrofuran / 1 h / 20 °C

7.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; lithium chloride; sodium carbonate / water; 1,4-dioxane / 1 h / 100 °C / Inert atmosphere

8.1: hydrogenchloride / methanol; dichloromethane; 1,4-dioxane / 3 h / 20 °C

9.1: sodium tris(acetoxy)borohydride / dichloromethane / 1 h / 0 - 10 °C / Inert atmosphere; Large scale

9.2: 0 - 10 °C / Inert atmosphere; Large scale

9.3: 0.5 h / Large scale

With pyridine; hydrogenchloride; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; N-iodo-succinimide; copper(l) iodide; palladium 10% on activated carbon; hydrogen; sodium tris(acetoxy)borohydride; sodium carbonate; caesium carbonate; trans-N,N'-dimethylcyclohexane-1,2-diamine; trifluoroacetic acid; lithium chloride; sodium nitrite; In tetrahydrofuran; 1,4-dioxane; methanol; ethanol; dichloromethane; water; N,N-dimethyl-formamide; toluene;

upstream raw materials:

N-(3-amino-2,6-difluorophenyl)acetamide

N-(2,6-difluoro-3-nitrophenyl)acetamide

N-(2,6-difluoro-3-(propylsulfonamido)phenyl)acetamide

N-(2,4-difluoro-3-iodophenyl) propane-1-sulfonamide

Refernces

• 1、 -. "NEW AZAINDOLYLPHENYL SULFONAMIDES AS SERINE/THREONINE KINASE INHIBITORS". Page/Page column 65. . Retrieved 2012/08/27.