75820-08-5

Basic information

• Product Name: Zidapamide
• Synonyms: ZIDAPUMIDE;Zidapamide;4-Chloro-N-(1-methyl-1,3-dihydroisoindol-2-yl)-3-sulfamoylbenzamide;3-(Aminosulfonyl)-4-chloro-N-(1,3-dihydro-1-methyl-2H-isoindol-2-yl)benzamide;4-Chloro-N-(1,3-dihydro-1-methyl-2H-isoindol-2-yl)-3-sulfamoylbenzamide;Isodapamide
• CAS NO: 75820-08-5
• Molecular Formula: C₁₆H₁₆ClN₃O₃S
• Molecular Weight: 365.83
• EINECS: 278-321-2
• Mol File: 75820-08-5.mol
• Article Data: 1

Chemical Properties

• Appearance: /
• Density: 1.51g/cm³
• Refractive Index: 1.693
• CAS DataBase Reference: Zidapamide(CAS DataBase Reference)
• NIST Chemistry Reference: Zidapamide(75820-08-5)
• EPA Substance Registry System: Zidapamide(75820-08-5)

Safety Data

• Hazardous Substances Data: 75820-08-5(Hazardous Substances Data)

Usage

Originator

Zidapamide,ZYF Pharm Chemical

Uses

Zidapamide is a thiazide-like diuretic drug used in treatment of hypertension.

Manufacturing Process

5.6 ml of triethylamine are added to a solution of 5.0 g (0.018 m) of α- methyl-α,α-dibromo-o-xylene and 2.38 g (0.018 m) of t-butylcarbazate in 15 ml of dimethylformamide heated to 50-60°C. After the addition, the mixture is left stirring for 3 h at room temperature, the solution volume is then made up to about 60 ml by diluting with H 2 O and the solution is left for a further hour under stirring. The solid which separates is filtered off, washed with water and dried to give 3.14 g (70%) of 1-methyl-N-(t-butyloxycarbonylamino) isoindoline, melting point 143-145°C.A suspension of 2.6 g (0.0104 m) of the 1-methyl-N-(t- butyloxycarbonylamino)isoindoline in 7 ml of concentrated HCl is kept stirring at room temperature for 1 h. The final solution is evaporated to dryness under vacuum by heating to 60-70°C to give a solid residue (1.97 g) which crystalises from EtOH+Et 2 O (1/1) to give 1.5 g (77.6%) of 1-methyl-2-amine isoindoline hydrochloride, melting point 140-145°C. 3.44 g (0.0 135 m) of 4-chloro-3-sulfamidobenzoic acid chloride are added to a solution of 2.5 g (0.0135 m) of 1-methyl-2-aminoisoindoline hydrochloride and 3.5 g (0.0314 m) of triethylamine in 30 ml of tetrahydrofuran. The mixture is kept stirring at room temperature for 15 h. The abundant solid which separates is filtered off, and is suspended in water in order to remove the triethylamine hydrochloride present. The residue is collected by filtration and dried in a drier to give 3.0 g of 1-methyl-2-(3'-sulfamyl-4'- chlorobenzamido)isoindoline, melting point 208-210°C (the analytical sample crystallizes from 10 volumes of ethyl alcohol, and has a melting point of 210- 212°C). A further amount (0.4 g) of product can be isolated by evaporating the tetrahydrofuran reaction solution, mixing the oily residue with ethyl alcohol and allowing it to crystallize in a refrigerator. The overall yield is 3.4 g, equal to 68.6%.

Therapeutic Function

Antihypertensive

InChI:InChI=1/C16H16ClN3O3S/c1-10-13-5-3-2-4-12(13)9-20(10)19-16(21)11-6-7-14(17)15(8-11)24(18,22)23/h2-8,10H,9H2,1H3,(H,19,21)(H2,18,22,23)

Upstream product

• 75820-06-3 1-methyl-2-<(tert-butyloxycarbonyl)amino>isoindoline 
• 35106-84-4 1-bromomethyl-2-(α-bromoethyl)benzene 
• 70049-77-3 3-(aminosulfonyl)-4-chlorobenzoyl chloride 
• 75820-07-4 1-methyl-2-aminoisoindoline hydrochloride 

Relevant articles and documents

Diuretic Agents Related to Indapamide. 1. Synthesis and Activity of 1-Substituted 2-(4-Chloro-3-sulfamoylbenzamido)isoindolines

The synthesis of isoindoline analogues of indapamide is described.These substances (4a,c,d) were tested for diuretic activity, and 4a was found to be comparable in potency to indapamide.