28328-54-3

Basic information

• Product Name: 3-amino-5-(aminosulphonyl)-4-phenoxybenzoic acid
• Synonyms: 3-amino-5-(aminosulphonyl)-4-phenoxybenzoic acid;BUTMETANIDERELATEDA;3-Amino-4-phenoxy-5-sulfamoylbenzoic Acid;Desbutyl Bumetanide;Desbutylbumetanide;PF 1578;BuMetanide related coMpound A (Desbutyl);Benzoic acid,3-aMino-5-(aMinosulfonyl)-4-phenoxy
• CAS NO: 28328-54-3
• Molecular Formula: C₁₃H₁₂N₂O₅S
• Molecular Weight: 308.30978
• EINECS: 248-971-1
• Product Categories: Chemical Amines;Amines;Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals;Sulfur & Selenium Compounds
• Mol File: 28328-54-3.mol
• Article Data: 6

Chemical Properties

• Boiling Point: 555.3°Cat760mmHg
• Flash Point: 289.6°C
• Appearance: /
• Density: 1.512g/cm³
• Vapor Pressure: 3.65E-13mmHg at 25°C
• Refractive Index: 1.663
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• Solubility: Acetone (Slightly), DMSO (Slightly), Ethyl Acetate (Slightly), Methanol (Slightl
• PKA: 3.91±0.10(Predicted)
• Stability: Hygroscopic
• CAS DataBase Reference: 3-amino-5-(aminosulphonyl)-4-phenoxybenzoic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 3-amino-5-(aminosulphonyl)-4-phenoxybenzoic acid(28328-54-3)
• EPA Substance Registry System: 3-amino-5-(aminosulphonyl)-4-phenoxybenzoic acid(28328-54-3)

Safety Data

• Hazardous Substances Data: 28328-54-3(Hazardous Substances Data)

Usage

InChI:InChI=1/C13H12N2O5S/c14-10-6-8(13(16)17)7-11(21(15,18)19)12(10)20-9-4-2-1-3-5-9/h1-7H,14H2,(H,16,17)(H2,15,18,19)

Synthetic route

3-nitro-4-phenoxy-5-sulfamoylbenzoic acid (28328-53-2) → 3-amino-5-(aminosulfonyl)-4-phenoxybenzoic acid (28328-54-3)

Conditions	Yield
Stage #1: 3-nitro-4-phenoxy-5-sulfamoylbenzoic acid With lithium hydroxide; hydrogen; palladium 10% on activated carbon In water at 20℃; for 16h; pH=8; Stage #2: With hydrogenchloride In water pH=3;	75%
palladium In ethanol	3.2 g (94%)
palladium In ethanol
With methanol; ammonium chloride; zinc In tetrahydrofuran at 20℃; Inert atmosphere;
palladium In ethanol	3.2 g (94%)

Pd + 3-nitro-4-phenoxy-5-sulfamoylbenzoic acid (28328-53-2) → 3-amino-5-(aminosulfonyl)-4-phenoxybenzoic acid (28328-54-3)

Conditions	Yield
With lithium hydroxide; palladium In water

3-amino-4-phenoxy-5-sulphamyl-benzamide (28394-99-2) → 3-amino-5-(aminosulfonyl)-4-phenoxybenzoic acid (28328-54-3)

Conditions	Yield
With sodium hydroxide

phenol (108-95-2) → 3-amino-5-(aminosulfonyl)-4-phenoxybenzoic acid (28328-54-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium hydrogencarbonate / water / 85 °C 1.2: 20 °C 2.1: zinc; ammonium chloride; methanol / tetrahydrofuran / 20 °C / Inert atmosphere View Scheme

4-chloro-3-nitro-5-sulfamoylbenzoic acid (22892-96-2) → 3-amino-5-(aminosulfonyl)-4-phenoxybenzoic acid (28328-54-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium hydrogencarbonate / water / 85 °C 1.2: 20 °C 2.1: zinc; ammonium chloride; methanol / tetrahydrofuran / 20 °C / Inert atmosphere View Scheme

3-amino-5-(aminosulfonyl)-4-phenoxybenzoic acid (28328-54-3) + butan-1-ol (71-36-3) → Bumetanide (28395-03-1)

Conditions	Yield
With iron(III) chloride; boron trifluoride diethyl etherate at 20℃; for 6h; Reagent/catalyst;	95.8%

4-heptanone (123-19-3) + 3-amino-5-(aminosulfonyl)-4-phenoxybenzoic acid (28328-54-3) → 3-(heptan-4-ylamino)-4-phenoxy-5-sulfamoyl-benzoic acid (1357459-06-3)

Conditions	Yield
Stage #1: 4-heptanone; 3-amino-5-(aminosulfonyl)-4-phenoxybenzoic acid With acetic acid; sodium sulfate at 70℃; for 4h; Stage #2: With sodium tris(acetoxy)borohydride; acetic acid at 40℃;	38%

ethanol (64-17-5) + 3-amino-5-(aminosulfonyl)-4-phenoxybenzoic acid (28328-54-3) + propargyl bromide (106-96-7) → ethyl-4-phenoxy-3-propargylamino-5-sulphamyl-benzoate (28395-25-7)

Conditions	Yield
Heating;

3-amino-5-(aminosulfonyl)-4-phenoxybenzoic acid (28328-54-3) → 4-phenoxy-3-propargylamino-5-sulphamyl-benzoic acid (28395-26-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: Heating 2: sodium hydroxide View Scheme

3-amino-5-(aminosulfonyl)-4-phenoxybenzoic acid (28328-54-3) + allyl bromide (106-95-6) → ethyl-3-allylamino-4-phenoxy-5-sulphamyl-benzoate (28395-23-5)

Conditions	Yield
In ethanol

piperonal (120-57-0) + 3-amino-5-(aminosulfonyl)-4-phenoxybenzoic acid (28328-54-3) → PF-1659 (28395-20-2)

Conditions	Yield
toluene-4-sulfonic acid In water; acetic acid

1-bromo-hexane (111-25-1) + 3-amino-5-(aminosulfonyl)-4-phenoxybenzoic acid (28328-54-3) + hexan-1-ol (111-27-3) → n-hexyl-3-n-hexylamino-4-phenoxy-5-sulphamyl-benzoate (28395-21-3)

Conditions	Yield
With methanesulfonic acid

3-amino-5-(aminosulfonyl)-4-phenoxybenzoic acid (28328-54-3) + ethyl iodide (75-03-6) → 3-ethylamino-4-phenoxy-5-sulphamyl-benzoic acid (28395-29-1)

Conditions	Yield
In sodium hydroxide; diethyl ether; ethanol

3-amino-5-(aminosulfonyl)-4-phenoxybenzoic acid (28328-54-3) + butyryl chloride (141-75-3) → 3-n-butyrylamino-4-phenoxy-5-sulfamyl-benzoic acid (56106-56-0)

Conditions	Yield
With pyridine; hydrogenchloride In 1,4-dioxane; (2S)-N-methyl-1-phenylpropan-2-amine hydrate; acetic acid; acetone

pentan-1-ol (71-41-0) + 3-amino-5-(aminosulfonyl)-4-phenoxybenzoic acid (28328-54-3) → n-Pentyl-3-n-pentylamino-4-phenoxy-5-sulphamyl-benzoate (28395-30-4)

Conditions	Yield
With conc. sulphuric acid

3-amino-5-(aminosulfonyl)-4-phenoxybenzoic acid (28328-54-3) + 3-amino-4-phenylthio-5-sulphamyl-benzoic acid (28772-65-8) → 3-benzylamino-4-phenoxy-5-sulphamyl-benzoic acid (28395-11-1)

1-bromo-4-butene (5162-44-7) + 3-amino-5-(aminosulfonyl)-4-phenoxybenzoic acid (28328-54-3) → 3-(but-3-enylamino)-4-phenoxy-5-sulfamylbenzoic acid (69145-53-5)

Conditions	Yield
With toluene-4-sulfonic acid In methanolic KOH; homoalylic alcohol	3.1 g (35%)

3-amino-5-(aminosulfonyl)-4-phenoxybenzoic acid (28328-54-3) + 2,5-hexanedione (110-13-4) → 3-Sulphamoyl-4-phenoxy-5-(2,5-dimethyl-1-pyrrolyl)-benzoic acid (67641-63-8)

Conditions	Yield
In water; acetic acid; ethyl acetate; acetone; benzene

copper-II chloride (CuCl2.2H2 O) + 3-amino-5-(aminosulfonyl)-4-phenoxybenzoic acid (28328-54-3) + 2-propenamide (79-06-1) → 3-Sulphamoyl-4-phenoxy-5-[β-(1-pyrrolyl)-ethyl]-benzoic acid (67641-47-8)

Conditions	Yield
With zinc; sodium nitrite In hydrogenchloride; water; acetic acid; acetone

3-amino-5-(aminosulfonyl)-4-phenoxybenzoic acid (28328-54-3) + methyl vinyl ketone (78-94-4) → 3-(γ-oxobutylamino)-4-phenoxy-5-sulfamylbenzoic acid (69145-50-2)

Conditions	Yield
In ethanol	5.05 g (82%)

(E)-1,4-dibromobutene (821-06-7) + 3-amino-5-(aminosulfonyl)-4-phenoxybenzoic acid (28328-54-3) → 3-(4-bromo-trans-2-butenylamino)-4-phenoxy-5-sulfamylbenzoic acid (69145-51-3)

Conditions	Yield
With acetic acid In 1,4-dioxane; methanol; chloroform; benzene

3-amino-5-(aminosulfonyl)-4-phenoxybenzoic acid (28328-54-3) + 4-Chlorobutanoyl chloride (4635-59-0) → 3-(γ-chlorobutyrylamino)-4-phenoxy-5-sulfamylbenzoic acid (69484-49-7)

Conditions	Yield
In 1,4-dioxane

cis,trans-2,5-dimethoxytetrahydrofuran (696-59-3) + 3-amino-5-(aminosulfonyl)-4-phenoxybenzoic acid (28328-54-3) → 4-phenoxy-3-(1H-pyrrol-1-yl)-5-sulphamoylbenzoic acid (67641-46-7)

Conditions	Yield
In acetic acid

acetoxymethylvinyl ketone + 3-amino-5-(aminosulfonyl)-4-phenoxybenzoic acid (28328-54-3) → 3-(γ-oxo-δ-acetoxybutylamino)-4-phenoxy-5-sulfamylbenzoic acid (69145-54-6)

Conditions	Yield
In ethanol	6.45 g (91%)

3-amino-5-(aminosulfonyl)-4-phenoxybenzoic acid (28328-54-3) + butan-1-ol (71-36-3) → 3-amino-4-phenoxy-5-sulfamoyl-benzoic acid butyl ester (61658-51-3)

Conditions	Yield
sulfuric acid Molecular sieve; Heating / reflux;

3-amino-5-(aminosulfonyl)-4-phenoxybenzoic acid (28328-54-3) → 3-(2-oxo-1-pyrrolidinyl)-4-phenoxy-5-sulfamylbenzoic acid (89995-78-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1,4-dioxane 2: potassium carbonate / 1,4-dioxane; dichloromethane; water View Scheme

Upstream product

• 2840-28-0 3-amino-4-chloro-benzoic acid 
• 28395-11-1 3-benzylamino-4-phenoxy-5-sulphamyl-benzoic acid 
• 32633-10-6 3-(4-Methoxy-benzylamino)-4-phenoxy-5-sulfamoyl-benzoesaeure 
• 22892-96-2 4-chloro-3-nitro-5-sulfamoylbenzoic acid 
• 108-95-2 phenol 
• 28394-99-2 3-amino-4-phenoxy-5-sulphamyl-benzamide 
• 28328-53-2 3-nitro-4-phenoxy-5-sulfamoylbenzoic acid 

Downstream Products

• 28395-23-5 ethyl-3-allylamino-4-phenoxy-5-sulphamyl-benzoate 
• 28395-29-1 3-ethylamino-4-phenoxy-5-sulphamyl-benzoic acid 
• 56106-56-0 3-n-butyrylamino-4-phenoxy-5-sulfamyl-benzoic acid 
• 28395-30-4 n-Pentyl-3-n-pentylamino-4-phenoxy-5-sulphamyl-benzoate 
• 28395-11-1 3-benzylamino-4-phenoxy-5-sulphamyl-benzoic acid 
• 67641-47-8 3-Sulphamoyl-4-phenoxy-5-[β-(1-pyrrolyl)-ethyl]-benzoic acid 
• 69145-50-2 3-(γ-oxobutylamino)-4-phenoxy-5-sulfamylbenzoic acid 
• 69484-49-7 3-(γ-chlorobutyrylamino)-4-phenoxy-5-sulfamylbenzoic acid 
• 61658-51-3 3-amino-4-phenoxy-5-sulfamoyl-benzoic acid butyl ester 
• 1357459-06-3 3-(heptan-4-ylamino)-4-phenoxy-5-sulfamoyl-benzoic acid 
• 28395-03-1 Bumetanide 
• 89995-78-8 3-(2-oxo-1-pyrrolidinyl)-4-phenoxy-5-sulfamylbenzoic acid 
• 67641-46-7 4-phenoxy-3-(1H-pyrrol-1-yl)-5-sulphamoylbenzoic acid 
• 69145-51-3 3-(4-bromo-trans-2-butenylamino)-4-phenoxy-5-sulfamylbenzoic acid 

Relevant articles and documents

Synthesis method of intermediate of bumetanib

The invention discloses a synthesis method of an intermediate of bumetanib. The comprises the following steps: protecting amino in 3-amino-4-chlorobenzoic acid as shown in a formula 1 by using a compound containing a benzyl protecting group to obtain a compound as shown in a formula 2; reacting the compound as shown in the formula 2 with thionyl chloride, and treating with ammonia water to obtain a compound as shown in a formula 3; reacting the compound as shown in the formula 3 with phenol to obtain a compound as shown in a formula 4; and reacting the compound as shown in the formula 4 with an oxidizing agent to obtain a bumetanib intermediate as shown in a formula 5, namely 3-amino-4-phenoxy-5-sulfamoyl benzoic acid. Compared with the prior art, the method provided by the invention has the advantages that the use of highly toxic chlorosulfonic acid is avoided, the nitration reaction is avoided, the production organization is facilitated, and the production safety is improved.

SUBSTITUTED ANTHRANILIC ACIDS

Disclosed herein are substituted anthranilic acids, pharmaceutically acceptable salts and prodrugs thereof, the chemical synthesis thereof, and medical use of such compounds for the treatment and/or management of hypertension, edema associated with congestive heart failure, hepatic disease, renal disease including nephrotic syndrome, or clearance of toxic substances from the body.

COMPOUNDS FOR TREATING HYPERTENSION

Compounds of the formula STR1 and their pharmaceutically acceptable salts, wherein the substituents are as defined herein, having antihypertensive activity.