16673-34-0

Basic information

• Product Name: 4-(2-(5-Chloro-2-methoxybenzamido)ethyl)benzenesulfamide
• Synonyms: 4-(2-(5-Chloro-2-methoxybenzamido)ethyl)benzenesulfamide;5-chloro-2-methoxy-n-(2-(4-sulfamoyl-phenyl)ethyl;N-(2-(4-(Aminosulfonyl)phenyl)ethyl)-5-chloro-2-methoxybenzamide;4-(5-CHLORO-2-METHOXYBENZAMIDOETHYL)BENZENESULFONAMIDE;4-[2-(5-CHLORO-2-METHOXY-BENZAMIDE)ETHYL]-BENZENESULPHONAMIDE;4-(2-(5-CHLORO-2-METHOXYBENZAMIDO)ETHYL)PHENYLSULFONAMIDE;4-[2-(5-CHLORO-2-METHOXYBENZAMIDO)ETHYL]PHENYLSULPHONAMIDE;4-[2-(2-METHOXY-5-CHLOROBENZAMIDO)ETHYL]BENZENESULFONAMIDE
• CAS NO: 16673-34-0
• Molecular Formula: C₁₆H₁₇ClN₂O₄S
• Molecular Weight: 368.84
• EINECS: 240-722-5
• Product Categories: Organic Building Blocks;Sulfonamides/Sulfinamides;Sulfur Compounds;Aromatics;Intermediates & Fine Chemicals;Pharmaceuticals;Aromatics,Pharmaceuticals;Building Blocks;Chemical Synthesis;Organic Building Blocks;Sulfur Compounds
• Mol File: 16673-34-0.mol
• Article Data: 12

Chemical Properties

• Melting Point: 209-214 °C
• Appearance: Light yellow solid
• Density: 1.357 g/cm³
• Refractive Index: 1.597
• Storage Temp.: Refrigerator
• Solubility: Soluble in DMSO (up to 45 mg/ml).
• PKA: 10.14±0.10(Predicted)
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 3 months.
• CAS DataBase Reference: 4-(2-(5-Chloro-2-methoxybenzamido)ethyl)benzenesulfamide(CAS DataBase Reference)
• NIST Chemistry Reference: 4-(2-(5-Chloro-2-methoxybenzamido)ethyl)benzenesulfamide(16673-34-0)
• EPA Substance Registry System: 4-(2-(5-Chloro-2-methoxybenzamido)ethyl)benzenesulfamide(16673-34-0)

Safety Data

• Hazard Codes: T
• Statements: 23-24-25
• Safety Statements: 24/25
• WGK Germany: 1
• Hazardous Substances Data: 16673-34-0(Hazardous Substances Data)

Usage

Description

4-(2-(5-Chloro-2-methoxybenzamido)ethyl)benzenesulfamide, also known as NLRP3i (16673-34-0), is an organic building block and NLRP3 inflammasome inhibitor. It is an intermediate in the synthesis of glyburide and has been reported to exhibit promising in vivo protective activities in mouse acute myocardial infarction models. This light yellow solid interferes with the formation of the NLRP3 inflammasome complex, blocking ASC aggregation and the release of IL-1β and the activation of caspase-1 in macrophages expressing constitutively active NLRP3.
Used in Pharmaceutical Industry:
4-(2-(5-Chloro-2-methoxybenzamido)ethyl)benzenesulfamide is used as an NLRP3 inflammasome inhibitor for its potential therapeutic effects in acute myocardial infarction and other inflammatory conditions. It helps limit infarct size after myocardial ischemia-reperfusion and reduces leukocyte infiltration in a peritonitis model in mice, making it a promising candidate for the development of anti-inflammatory drugs.
Used in Drug Synthesis:
4-(2-(5-Chloro-2-methoxybenzamido)ethyl)benzenesulfamide is used as an intermediate in the synthesis of glyburide, a medication used to treat type 2 diabetes. Its role in the synthesis process contributes to the development of pharmaceuticals for managing blood sugar levels in patients with diabetes.

References

1) Fulp?et al.?(2018),?Structural Insights of Benzenesulfonamide Analogues as NLRP3 Inflammasome Inhibitors: Design, Synthesis, and Biological Characterization; J. Med. Chem.,?61?5412 2) Marchetti?et al.?(2014),?A novel pharmacologic inhibitor of the NLRP3 inflammasome limits myocardial injury after ischemia-reperfusion in the mouse; J. Cardiovas. Pharmacol.,?63?316

InChI:InChI=1/C16H17ClN2O4S/c1-23-15-7-4-12(17)10-14(15)16(20)19-9-8-11-2-5-13(6-3-11)24(18,21)22/h2-7,10H,8-9H2,1H3,(H,19,20)(H2,18,21,22)

Upstream product

• 29568-33-0 2-methoxy-5-chlorobenzoyl chloride 
• 35303-76-5 4-(2-aminoethyl)benzenesulfonamide 
• 223253-87-0 4-[2-(2,2,2-trifluoroacetamido)ethyl]benzenesulfonyl chloride 
• 458-85-5 2,2,2-trifluoro-N-(2-phenylethyl)acetamide 
• 33924-54-8 4-(2-[(5-chloro-2-methoxyphenyl)formamido]ethyl)benzene-1-sulfonyl chloride 
• 33924-49-1 DK₁₃ 
• 64-04-0 phenethylamine 
• 3438-16-2 5-chloro-2-methoxybenzoic acid 
• 10238-21-8 Glibenclamid 
• 14497-76-8 4-[4-(β-{2-methoxy-5-chlorobenzamido}-ethyl)benzenesulfonyl]-1.1-pentamethylene-semicarbazide 
• 85-44-9 phthalic anhydride 

Downstream Products

• 59478-18-1 C₂₅H₃₂ClN₃O₄S₂ 
• 23749-20-4 C₂₄H₂₈ClN₃O₅S 
• 14511-59-2 Ethyl 4-<2-(5-chloro-2-methoxybenzamido)ethyl>benzenesulfonamidecarbamate 
• 1202020-07-2 N-{4-[N-(2-bromobenzylcarbamoyl)sulfamoyl]-phenethyl}-5-chloro-2-methoxybenzamide 
• 10238-21-8 Glibenclamid 
• 33924-54-8 4-(2-[(5-chloro-2-methoxyphenyl)formamido]ethyl)benzene-1-sulfonyl chloride 
• 59588-58-8 5-Chloro-2-methoxy-N-[2-(4-sulfamoyl-phenyl)-propyl]-benzamide 
• 18188-38-0 C₂₆H₃₄ClN₃O₅S 

Relevant articles and documents

Influence of blood proteins on biomedical analysis. IX. Protective effects of human serum proteins on anion-induced degradation of gliclazide

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Total Synthesis of Glipizide and Glibenclamide in Continuous Flow

Glipizide and glibenclamide remain some of the widely prescribed antidiabetic sulfonylurea drugs for the treatment of type 2 diabetes mellitus. Herein the authors report on an isocyanate-free synthetic procedure towards the preparation of these on demand drugs at multigram scale using continuous flow technology. The safety concern over the use of isocyanates in most of the existing synthetic routes was dealt with in this present work by using N-carbamates synthesised in situ from activation of amines with chloroformates as safer alternatives. An overall yield of 80–85 % was obtained for the semi-telescoped steps within 10 min total residence time.

Synthesis method of glibenclamide

The invention discloses a synthesis method of glibenclamide, which includes the steps of: 1) protection of amino groups with trichloroacetic anhydride; 2) sulfonation; 3) sulfo-amidation; 4) amidation: performing a reaction to 5-chloro-2-methoxybenzoic acid with N,N-carbonyl diimidazole and performing a reaction to the product with a compound (III) under effect of a second acid-binding agent; 5) addition: adding the second acid-binding agent and crown ether, in catalytic amount, to perform an addition reaction to a compound (IV) with cyclohexyl isocyanate to prepare the glibenclamide. The method is high in yields in all steps, wherein residue of impurities is effectively reduced during processes of protection, deprotection, acid treatment, alkali treatment and water-adding separation of the substrate. According to the method, a phase-transfer catalyst is matched with the second acid-binding agent, so that compatibility between the isocyanate and the compound (IV) is effectively increased, and the nucleophilic reaction is carried out more completely. The produced product is higher in purity.

Design and Performance Validation of a Conductively Heated Sealed-Vessel Reactor for Organic Synthesis

A newly designed robust and safe laboratory scale reactor for syntheses under sealed-vessel conditions at 250 °C maximum temperature and 20 bar maximum pressure is presented. The reactor employs conductive heating of a sealed glass vessel via a stainless steel heating jacket and implements both online temperature and pressure monitoring in addition to magnetic stirring. Reactions are performed in 10 mL borosilicate vials that are sealed with a silicone cap and Teflon septum and allow syntheses to be performed on a 2-6 mL scale. This conductively heated reactor is compared to a standard single-mode sealed-vessel microwave instrument with respect to heating and cooling performance, stirring efficiency, and temperature and pressure control. Importantly, comparison of the reaction outcome for a number of different synthetic transformations performed side by side in the new device and a standard microwave reactor suggest that results obtained using microwave conditions can be readily mimicked in the operationally much simpler and smaller conventionally heated device.