74534-15-9

Basic information

• Product Name: 1-chloro-2-iodo-4-nitro-benzene
• Synonyms: 1-chloro-2-iodo-4-nitro-benzene;Nsc223078
• CAS NO: 74534-15-9
• Molecular Formula: C₆H₃ClINO₂
• Molecular Weight: 283.45
• EINECS: 200-258-5
• Mol File: 74534-15-9.mol
• Article Data: 23

Chemical Properties

• Melting Point: 78 °C
• Boiling Point: 315.7 °C at 760 mmHg
• Flash Point: 144.7 °C
• Appearance: /
• Density: 2.094 g/cm³
• Storage Temp.: 2-8°C(protect from light)
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• CAS DataBase Reference: 1-chloro-2-iodo-4-nitro-benzene(CAS DataBase Reference)
• NIST Chemistry Reference: 1-chloro-2-iodo-4-nitro-benzene(74534-15-9)
• EPA Substance Registry System: 1-chloro-2-iodo-4-nitro-benzene(74534-15-9)

Safety Data

• HazardClass: IRRITANT
• Hazardous Substances Data: 74534-15-9(Hazardous Substances Data)

Usage

Description

1-Chloro-2-iodo-4-nitro-benzene is an organic compound characterized by its molecular structure that features a chlorine atom at the 1st position, an iodine atom at the 2nd position, and a nitro group at the 4th position on a benzene ring. It is a synthetic chemical used as a key intermediate in the pharmaceutical industry.

Uses

Used in Pharmaceutical Industry:
1-Chloro-2-iodo-4-nitro-benzene is used as a chemical intermediate for the synthesis of Vismodegib (V674700) and Vismodegib-d4 (V674702). These are pharmaceuticals that specifically target the hedgehog (Hh) signaling pathway, which plays a crucial role in various developmental processes and is associated with certain types of cancer. By inhibiting the Hh pathway, Vismodegib and its derivatives can potentially treat or manage conditions related to the abnormal activation of this pathway.

InChI:InChI=1/C6H3ClINO2/c7-5-2-1-4(9(10)11)3-6(5)8/h1-3H

Upstream product

• 2516-96-3 2-chloro-5-nitrobenzoic acid 
• 615-41-8 2-iodochlorobenzene 
• 7697-37-2 nitric acid 
• 100-00-5 4-chlorobenzonitrile 
• 6293-83-0 2-iodo-4-nitrophenylamine 
• 6283-25-6 H₂NC₆H₃(Cl)NO₂ 

Downstream Products

• 671788-93-5 1-chloro-2-iodo-4,5-dinitro-benzene 
• 1033931-98-4 4-(2-chloro-5-nitrophenyl)-butan-2-one 
• 1314306-02-9 2-chloro-N-(4-chloro-3-iodophenyl)-4-methylsulfonylbenzamide 
• 1370525-64-6 2-chloro-N-[4-chloro-3-(5-hydroxy-2-pyridyl)phenyl]-4-methylsulfonylbenzamide 
• 879088-40-1 2-(2-chloro-5-nitrophenyl)-pyridine 

Relevant articles and documents

Selective Late-Stage Oxygenation of Sulfides with Ground-State Oxygen by Uranyl Photocatalysis

Oxygenation is a fundamental transformation in synthesis. Herein, we describe the selective late-stage oxygenation of sulfur-containing complex molecules with ground-state oxygen under ambient conditions. The high oxidation potential of the active uranyl cation (UO22+) enabled the efficient synthesis of sulfones. The ligand-to-metal charge transfer process (LMCT) from O 2p to U 5f within the O=U=O group, which generates a UV center and an oxygen radical, is assumed to be affected by the solvent and additives, and can be tuned to promote selective sulfoxidation. This tunable strategy enabled the batch synthesis of 32 pharmaceuticals and analogues by late-stage oxygenation in an atom- and step-efficient manner.

Design, synthesis and biological evaluation of deuterated Vismodegib for improving pharmacokinetic properties

Vismodegib is an oral and high selective hedgehog (Hh) inhibitor used for the treatment of basal cell carcinoma (BCC). In this work, analogs of Vismodegib with deuterium-for-hydrogen replacement at certain metabolically active sites were prepared and found to have a better pharmacokinetic properties in mice. In particular, deuterated compound SKLB-C2211 obviously altered the blood circulation behavior compared to its prototype, which was demonstrated by significantly prolonged blood circulation half-life time (t1/2) and increased AUC0→∞. These results suggested SKLB-C2211 had the potential to be a long-acting inhibitor against Hh signaling pathway, and laid the foundation for the further research of its druggability.

Design, Synthesis, and Structure-Activity Relationship of Tetrahydropyrido[4,3-d]pyrimidine Derivatives as Potent Smoothened Antagonists with in Vivo Activity

Medulloblastoma is one of the most prevalent brain tumors in children. Aberrant hedgehog (Hh) pathway signaling is thought to be involved in the initiation and development of medulloblastoma. Vismodegib, the first FDA-approved cancer therapy based on inhibition of aberrant hedgehog signaling, targets smoothened (Smo), a G-protein coupled receptor (GPCR) central to the Hh pathway. Although vismodegib exhibits promising therapeutic efficacy in tumor treatment, concerns have been raised from its nonlinear pharmacokinetic (PK) profiles at high doses partly due to low aqueous solubility. Many patients experience adverse events such as muscle spasms and weight loss. In addition, drug resistance often arises among tumor cells during treatment with vismodegib. There is clearly an urgent need to explore novel Smo antagonists with improved potency and efficacy. Through a scaffold hopping strategy, we have identified a series of novel tetrahydropyrido[4,3-d]pyrimidine derivatives, which exhibited effective inhibition of Hh signaling. Among them, compound 24 is three times more potent than vismodegib in the NIH3T3-GRE-Luc reporter gene assay. Compound 24 has a lower melting point and much greater solubility compared with vismodegib, resulting in linear PK profiles when dosed orally at 10, 30, and 100 mg/kg in rats. Furthermore, compound 24 showed excellent PK profiles with a 72% oral bioavailability in beagle dogs. Compound 24 demonstrated overall favorable in vitro safety profiles with respect to CYP isoform and hERG inhibition. Finally, compound 24 led to significant regression of subcutaneous tumor generated by primary Ptch1-deficient medulloblastoma cells in SCID mouse. In conclusion, tetrahydropyrido[4,3-d]pyrimidine derivatives represent a novel set of Smo inhibitors that could potentially be utilized to treat medulloblastoma and other Hh pathway related malignancies.