N-(3-(5-(4-Chlorophenyl)-1H-pyrrolo[2,3-B]pyridine-3-carbonyl)-2,4-difluorophenyl)propane-1-sulfonaMide

Base Information

• Chemical Name: N-(3-(5-(4-Chlorophenyl)-1H-pyrrolo[2,3-B]pyridine-3-carbonyl)-2,4-difluorophenyl)propane-1-sulfonaMide
• CAS No.: 918504-65-1
• Molecular Formula: C₂₃H₁₈ClF₂N₃O₃S
• Molecular Weight: 489.93
• Hs Code.: 29339900
• Mol file: 918504-65-1.mol

Synonyms:PLX4032;RO5185426;N-[3-[5-(4-Chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl]propane-1-sulfonamide;1-Propanesulfonamide, N-[3-[[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]carbonyl]-2,4-difluorophenyl]-;Zelboraf;

Chemical Property of N-(3-(5-(4-Chlorophenyl)-1H-pyrrolo[2,3-B]pyridine-3-carbonyl)-2,4-difluorophenyl)propane-1-sulfonaMide

Chemical Property:

• PKA: 6.26±0.10(Predicted)
• PSA: 100.30000
• Density: 1.474 g/cm³
• LogP: 6.69800
• Storage Temp.: -20°C
• Solubility.: Soluble in DMSO (up to 100 mg/ml)

Purity/Quality:

99.0% ^*data from raw suppliers

Vemurafenib ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: In August 2011, the United States FDA approved vemurafenib (PLX- 4032, RO-5185426) for the treatment of patients with metastatic melanoma with the BRAFV600E mutation. Vemurafenib has been developed as a targeted therapy for patients with the BRAF gene mutation since oncogenic B-raf signaling is implicated in approximately 50% of melanomas. Vemurafenib was identified based on an initial high-throughput screen followed by the extensive use of structure-based drug design. Vemurafenib is a potent inhibitor of B-RafV600E kinase (IC50=13 nM) compared to its potency against wildtype B-raf (IC50=160 nM) and is fairly selective versus a panel of 200 kinases. It does inhibit other kinases (RAF1, SRMS, ACK1, MAP4K5, and FGR) and mutant B-raf kinases (BRAFV600K, BRAFV600D, and BRAFV600R) with enzyme IC50's of <100 nM.
• Uses: Vemurafenib selective BRAFV600E kinase inhibitor; an antitumor agent. Vemurafenib functions by inhibiting the proliferation and mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase and ERK phosphorylation in a panel of tumor cell lines, including melanoma cell lines expressing BRAFV600E or other mutant BRAF proteins altered at codon 600. Vemurafenib (PLX4032, RG7204) is a novel and potent inhibitor of B-RafV600E with IC50 of 31 nM PLX4032 is an orally bioavailable, ATP-competitive inhibitor of mutant V600E and wild type B-Raf kinases (IC50s = 31 and 100 nM, respectively). It inhibits cell proliferation in a variety of cell lines expressing B-Raf V600E and synergizes strongly with taxol, vinblastine, and oxaliplatin in inhibiting the proliferation of B-RafV600E transformed cancer cells. PLX4032 is effective against the growth of tumors bearing the B-Raf V600E mutation.[Cayman Chemical]

Technology Process of N-(3-(5-(4-Chlorophenyl)-1H-pyrrolo[2,3-B]pyridine-3-carbonyl)-2,4-difluorophenyl)propane-1-sulfonaMide

There total 51 articles about N-(3-(5-(4-Chlorophenyl)-1H-pyrrolo[2,3-B]pyridine-3-carbonyl)-2,4-difluorophenyl)propane-1-sulfonaMide 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: 95.0%

propane-1-sulfonic acid {3-[5-(4-chlorophenyl) 1-(2,6-dichloro-benzoyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide (1262985-23-8) → vemurafenib (1029872-54-5,918504-65-1)

Guidance literature:

With ammonia; In methanol; N,N-dimethyl acetamide; at 50 - 55 ℃; Inert atmosphere; Autoclave;

Reference yield: 92.0%

propane-1-sulfonic acid (3-{[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-yl]hydroxymethyl}-2,4-difluorophenyl)amide → vemurafenib (1029872-54-5,918504-65-1)

Guidance literature:

With 2,3-dicyano-5,6-dichloro-p-benzoquinone; In 1,4-dioxane; water; at 100 ℃; for 0.166667h; Microwave irradiation;

DOI:10.1016/j.tetlet.2012.05.137

Reference yield: 85.0%

5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine (918516-27-5) + 2,6-difluoro-3-(propane-1-sulfonylamino)benzoic acid (1103234-56-5) → vemurafenib (1029872-54-5,918504-65-1)

Guidance literature:

2,6-difluoro-3-(propane-1-sulfonylamino)benzoic acid; With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 20 ℃; for 2.5h;

5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine; aluminum (III) chloride; In dichloromethane; at 20 ℃; for 3h;

upstream raw materials:

propane-1-sulfonic acid {3-[5-(4-chlorophenyl) 1-(2,6-dichloro-benzoyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide

5-bromo-2-pyridylamine

4-Chlorophenylboronic acid

2,6-difluoro-3-(propane-1-sulfonylamino)benzoic acid

Downstream raw materials:

1-(5-(4-chlorophenyl)-3-(2,6-difluoro-3-(propylsulfonamido)benzoyl)-1H-pyrrolo[2,3-b]pyridin-1-yl)ethyl dihydrogen phosphate

(S)-2-amino-N-(3-(5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl)-3-methyl-N-(propylsulfonyl)butanamide hydrochloride

Refernces

• 1、 -. "NEW PROCESSES FOR THE PREPARATION OF VEMURAFENIB". Page/Page column 24. . Retrieved 2018/02/03.
• 2、 -. "SUBSTANTIALLY PURE VEMURAFENIB AND ITS SALTS". Page/Page column 26. . Retrieved 2016/06/14.