22503-72-6

Basic information

• Product Name: IDRA 21
• Synonyms: IDRA 21;7-CHLORO-3-METHYL-3,4-DIHYDRO-2H-1,2,4-BENZOTHIADIAZINE;7-CHLORO-3-METHYL-3,4-DIHYDRO-2H-1,2,4-BENZOTHIADIAZINE 1,1-DIOXIDE;7-CHLORO-3-METHYL-3,4-DIHYDRO-2H-1,2,4-BENZOTHIADIAZINE S,S-DIOXIDE;IDRA 21,98%;2H-1,2,4-Benzothiadiazine,7-chloro-3,4-dihydro-3-Methyl-, 1,1-dioxide;AMPAKINE;7-chloro-3-methyl-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide
• CAS NO: 22503-72-6
• Molecular Formula: C₈H₉ClN₂O₂S
• Molecular Weight: 232.69
• Mol File: 22503-72-6.mol
• Article Data: 3

Chemical Properties

• Melting Point: 209 °C(Solv: acetic acid (64-19-7))
• Boiling Point: 405.1°Cat760mmHg
• Flash Point: 198.8°C
• Appearance: /
• Density: 1.394g/cm³
• Vapor Pressure: 8.98E-07mmHg at 25°C
• Refractive Index: 1.571
• Storage Temp.: Store at RT
• Solubility: DMSO (Slightly), Methanol (Slightly, Sonicated)
• PKA: 9.78±0.40(Predicted)
• CAS DataBase Reference: IDRA 21(CAS DataBase Reference)
• NIST Chemistry Reference: IDRA 21(22503-72-6)
• EPA Substance Registry System: IDRA 21(22503-72-6)

Safety Data

• Safety Statements: 24/25
• WGK Germany: 3
• Hazardous Substances Data: 22503-72-6(Hazardous Substances Data)

Usage

Chemical Properties

white to off-white crystalline powder

Uses

Different sources of media describe the Uses of 22503-72-6 differently. You can refer to the following data:
1. IDRA-21 inhibits AMPA receptor desensitization and enhances cognition by a related mechanism. IDRA-21 is more able to cross the blood-brain barrier than Cyclothiazide (C988960).
2. IDRA-21 is a benzothiadiazine derivative and a positive allosteric modulator of glutamate AMPA receptors (1,2,3,4). It is able to increase excitatory synaptic strength by inhibiting AMPA receptor desensitization. IDRA 21 may exhibit therapeutic effects to ameliorate memory deficits in patients with cognitive impairments such as Alzheimer''s disease.

Biological Activity

Inhibits AMPA receptor desensitization and enhances cognition by a related mechanism. More able to cross the blood-brain barrier than cyclothiazide (6-Chloro-3,4-dihydro-3-(5-norbornen-2-yl)-2H-1,2,4-benzothiazidiazine-7-sulfonamide-1,1-dioxide ).

InChI:InChI=1/C8H9ClN2O2S/c1-5-10-7-3-2-6(9)4-8(7)14(12,13)11-5/h2-5,10-11H,1H3

Synthetic route

2-amino-5-chlorobenzenesulfonamide (5790-69-2) + ethanol (64-17-5) → IDRA 21 (22503-72-6)

Conditions	Yield
With tert.-butylhydroperoxide at 110℃; for 12h;	80%

2-amino-5-chlorobenzenesulfonamide (5790-69-2) + acetaldehyde (75-07-0) → IDRA 21 (22503-72-6)

Conditions	Yield
In acetonitrile
With camphorsulfonic acid In acetonitrile at 20℃; Sealed tube;

4-Chlor-2-acetylsulfamoyl-acetanilid (90794-87-9) → IDRA 21 (22503-72-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: aq. NaOH 2: acetonitrile View Scheme

2-acetylamino-benzenesulfonic acid acetylamide (17800-60-1) → IDRA 21 (22503-72-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: Cl2 / acetic acid 2: aq. NaOH 3: acetonitrile View Scheme

IDRA 21 (22503-72-6) → N-acetyl-5-chloro-2-nitrobenzenesulfonamide (19900-92-6)

Conditions	Yield
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 12h; Cooling with ice;	99%

IDRA 21 (22503-72-6) → 5-chloro-2-(ethylamino)benzenesulfonamide (38443-06-0)

Conditions	Yield
With sodium cyanoborohydride In acetic acid at 20℃; for 3h; regioselective reaction;	93%

IDRA 21 (22503-72-6) → 2-amino-5-chloro-N-ethylbenzenesulfonamide (5790-62-5)

Conditions	Yield
With sodium cyanoborohydride In ethanol; water at 70℃; for 6h; regioselective reaction;	86%

IDRA 21 (22503-72-6) → C16H14Cl2N4O6S2

Conditions	Yield
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 12h; Cooling with ice;	19%

IDRA 21 (22503-72-6) + methyl iodide (74-88-4) → (+/-)-7-chloro-2,3-dimethyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide (38442-77-2)

Conditions	Yield
With potassium carbonate In acetonitrile at 70 - 80℃;

Upstream product

• 5790-69-2 2-amino-5-chlorobenzenesulfonamide 
• 64-17-5 ethanol 
• 17800-60-1 2-acetylamino-benzenesulfonic acid acetylamide 
• 90794-87-9 4-Chlor-2-acetylsulfamoyl-acetanilid 
• 75-07-0 acetaldehyde 

Downstream Products

• 5790-62-5 2-amino-5-chloro-N-ethylbenzenesulfonamide 
• 38443-06-0 5-chloro-2-(ethylamino)benzenesulfonamide 
• 19900-92-6 N-acetyl-5-chloro-2-nitrobenzenesulfonamide 

Relevant articles and documents

Metal-free oxidative cyclization of 2-amino-benzamides, 2-aminobenzenesulfonamide or 2-(aminomethyl)anilines with primary alcohols for the synthesis of quinazolinones and their analogues

A general metal-free oxidative cyclization process has been developed for the synthesis of quinazolinones, benzothiadiazines and quinazolines. By this protocol, a range of substituted 2-aminobenzamides, 2-aminobenzenesulfonamide and 2-(aminomethyl)anilines react with various alcohols, leading to the desired annulated products smoothly. This protocol features many advantages as broad substrate scope, mild reaction conditions, low environmental pollution, high atom-economy and good to excellent yields.

ANTIHYPERTENSIVE AGENTS. I. NON-DIURETIC 2H-1,2,4-BENZOTHIADIAZINE

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