2-Chloro-N-[4-chloro-3-(2-pyridinyl)phenyl]-4-(methylsulfonyl)benzamide

Base Information

• Chemical Name: 2-Chloro-N-[4-chloro-3-(2-pyridinyl)phenyl]-4-(methylsulfonyl)benzamide
• CAS No.: 879085-55-9
• Molecular Formula: C₁₉H₁₄Cl₂N₂O₃S
• Molecular Weight: 421.304
• Hs Code.: 29333990
• Mol file: 879085-55-9.mol

Synonyms:GDC0449;Benzamide, 2-chloro-N-[4-chloro-3-(2-pyridinyl)phenyl]-4-(methylsulfonyl)-;2-Chloro-N-[4-chloro-3-(2-pyridinyl)phenyl]-4-(methylsulfonyl)benzamide;

Chemical Property of 2-Chloro-N-[4-chloro-3-(2-pyridinyl)phenyl]-4-(methylsulfonyl)benzamide

Chemical Property:

• Vapor Pressure: 1.22E-12mmHg at 25°C
• Refractive Index: 1.64
• Boiling Point: 561.6°C at 760 mmHg
• PKA: 10.72±0.70(Predicted)
• Flash Point: 293.4°C
• PSA: 84.51000
• Density: 1.440
• LogP: 5.86500
• Storage Temp.: -20°
• Solubility.: Soluble in DMSO (up to 200 mg/ml) or in Ethanol (up to 10 mg/ml with warming)

Purity/Quality:

99.9% ^*data from raw suppliers

Vismodegib ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: In January 2012, the US FDA approved vismodegib (also referred to as GDC-0449) for the treatment of adults with metastatic basal cell carcinoma (BCC), with locally advanced BCC that has recurred following surgery or who are not candidates for surgery or radiation. Vismodegib inhibits the Hh sig?naling pathway by functioning as an antagonist of SMO thereby inhibiting the activation of Hedgehog target genes, resulting in decreased downstream pro?duction of proliferation factors. The IC50 of vismodegib in a Hedgehog?responsive cell line derived from human embryonic palatal mesenchyme cells was 2.8 nM. In preclinical in vivostudies, vismodegib at 12.5 mg/kg (bid) caused complete regression of tumors in a Hh pathway dependent medulloblas?tomaallograft model generated from Ptch+/-mice. A synthesis of vismodegib starting from 2-chloro-5-nitro aniline and employing a Negishi coupling with 2-pyridyl zinc iodide as a key step has been reported.
• Uses: Targets the Hedgehog (Hh) pathway. Inhibition of the Hh signaling may be effective in the treatment and prevention of many types of human cancers. Vismodegib (GDC-0449) is a potent, novel and specific hedgehog inhibitor with IC50 of 3 nM and also inhibits P-gp with IC50 of 3.0 μM. Vismodegib targets the Hedgehog (Hh) pathway. Inhibition of the Hh signaling may be effective in the treatment and prevention of many types of human cancers. Potent Hedgehog inhibitor.
• Clinical Use: Antineoplastic agent: Treatment of basal cell carcinoma which is inappropriate for surgery or radiotherapy
• Drug interactions: Potentially hazardous interactions with other drugs Antibacterials: concentration possibly reduced by rifampicin - avoid. Antidepressants: concentration possibly reduced by St John’s wort - avoid. Antiepileptics: concentration possibly reduced by carbamazepine, fosphenytoin and phenytoin - avoid. Antipsychotics: avoid with clozapine, increased risk of agranulocytosis.

Technology Process of 2-Chloro-N-[4-chloro-3-(2-pyridinyl)phenyl]-4-(methylsulfonyl)benzamide

There total 75 articles about 2-Chloro-N-[4-chloro-3-(2-pyridinyl)phenyl]-4-(methylsulfonyl)benzamide 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: 92.2%

4-chloro-3-(pyridin-2-yl)benzeneamine (879088-41-2) + 2-chloro-4-(methylsulphonyl)benzoyl chloride (106904-10-3) → vismodegib (879085-55-9)

Guidance literature:

With triethylamine; In dichloromethane; at 0 - 20 ℃; for 8h;

Reference yield: 90.0%

4-methylsulfonyl-1-methyl-2-chlorobenzene (1671-18-7) + C11H8Cl2N2 → vismodegib (879085-55-9)

Guidance literature:

at 80 ℃; for 0.416667h;

Reference yield: 86.0%

2-chloro-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(methylthio)benzamide → vismodegib (879085-55-9)

Guidance literature:

With oxone||potassium monopersulfate triple salt; In methanol; water; at 20 ℃; Schlenk technique;

DOI:10.1021/acs.orglett.8b02677

upstream raw materials:

2-(3-nitrophenyl)pyridine

2-(2-chloro-5-nitrophenyl)-pyridine

4-chloro-3-(pyridin-2-yl)benzeneamine

2-chloro-4-(methylsulphonyl)benzoyl chloride

Downstream raw materials:

C₂₁H₁₆Cl₂N₂O₅S

C₂₁H₁₅Cl₂FN₂O₅S

Refernces

• 1、 Meng, Yingying,Wang, Ming,Jiang, Xuefeng. "Multicomponent Reductive Cross-Coupling of an Inorganic Sulfur Dioxide Surrogate: Straightforward Construction of Diversely Functionalized Sulfones". supporting information. p. 1346 - 1353. Retrieved 2019/12/11.
• 2、 -. "A [...] synthesis of intermediates method and application". Paragraph 0037; 0038; 0039; 0040. . Retrieved 2019/03/28.