33045-52-2

Usage

Uses

Used in Pharmaceutical Industry:
Methyl 2-methoxy-5-sulfamoylbenzoate is used as a reactant for the preparation of anticoagulants, which are medications that help prevent blood clots from forming. Its presence in these compounds aids in the inhibition of clot formation, thus reducing the risk of stroke, heart attack, and other thrombotic events.
Methyl 2-methoxy-5-sulfamoylbenzoate is also used as a reactant in the synthesis of HCV NS5B polymerase inhibitors. These inhibitors are crucial in the treatment of Hepatitis C virus infections, as they target and inhibit the viral polymerase enzyme, thereby suppressing viral replication and reducing the viral load in the body.
In the treatment of neurodegenerative diseases, Methyl 2-methoxy-5-sulfamoylbenzoate plays a role as a reactant in the development of therapeutic drugs. These drugs aim to slow down or halt the progression of neurodegenerative conditions such as Alzheimer's, Parkinson's, and Huntington's diseases by targeting specific cellular pathways and mechanisms involved in the disease process.
Lastly, Methyl 2-methoxy-5-sulfamoylbenzoate is utilized as a reactant in the production of oral hypoglycemic agents. These agents are essential in the management of diabetes, as they help lower blood sugar levels by stimulating insulin secretion or enhancing insulin sensitivity in the body. This contributes to better glucose control and overall management of diabetes.

InChI:InChI=1/C9H11NO5S/c1-14-8-4-3-6(16(10,12)13)5-7(8)9(11)15-2/h3-5H,1-2H3,(H2,10,12,13)

Synthetic route

methyl 5-chloro-2-methoxybenzoate (33924-48-0) → methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2)

Conditions	Yield
With sodium sulfamate; copper(I) bromide In tetrahydrofuran at 50℃; for 10h; Temperature; Reflux;	96.55%
With sodium aminosulfinate; copper(I) bromide In tetrahydrofuran at 40℃; for 18h; Concentration; Temperature;	96.55%
With sodium aminosulfinate; copper(l) chloride In tetrahydrofuran at 40℃; for 8h; Temperature;	96.55%

methanol (67-56-1) + 3-cyano-4-methoxybenzenesulfonamide (22117-84-6) → methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2)

Conditions	Yield
With hydrogenchloride at 40℃; for 6h; Time;	88.6%

methanol (67-56-1) + 2-methoxy-5-sulfamoylbenzoic acid (22117-85-7) → methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2)

Conditions	Yield
With hydrogenchloride

methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2) → 2-methoxy-5-sulfamoylbenzoic acid (22117-85-7)

Conditions	Yield
With sodium hydroxide In methanol	98.3%
Stage #1: methyl 2-methoxy-5-sulfamoyl-benzoate With sodium hydroxide; water In methanol at 20℃; for 1h; Stage #2: With hydrogenchloride In methanol; water	98.3%
Stage #1: methyl 2-methoxy-5-sulfamoyl-benzoate With sodium hydroxide; water In methanol at 20℃; for 1h; Stage #2: With hydrogenchloride In methanol; water	98.3%

ethanol (64-17-5) + methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2) → 2-methoxy-5-sulfamoylbenzoic acid ethyl ester (33045-53-3)

Conditions	Yield
With sulfuric acid for 12h; Heating;	98%

methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2) + (S)-2-(Aminomethyl)-1-ethylpyrrolidine (22795-99-9) → (S)-(-)-sulpiride (15676-16-1, 23672-06-2, 23672-07-3, 23756-79-8)

Conditions	Yield
at 90 - 100℃; for 5h; Inert atmosphere;	93.8%
With hydrogenchloride In water; butan-1-ol	75%

1-ethyl-2-pyrrolidinemethanamine (26116-12-1) + methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2) → N-[(1-ethyl-2-pyrrolidinyl)methyl]-2-methoxy-5-sulfamoylbenzamide (15676-16-1)

Conditions	Yield
In glycerol at 90 - 95℃; for 10h; Inert atmosphere;	88.4%
In ethylene glycol at 90 - 100℃; Solvent; Inert atmosphere;	85.1%
at 100℃; for 3h;	75%

methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2) + acetic anhydride (108-24-7) → methyl 5-(N-acetylsulfamoyl)-2-methoxybenzoate

Conditions	Yield
With zinc(II) chloride at 20℃;	77%

aminolupinane (2346-98-7, 10248-19-8, 15527-89-6, 22342-32-1, 46000-58-2, 75532-84-2, 145842-67-7) + methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2) → 2-Methoxy-N-[(1S,9aR)-1-(octahydro-quinolizin-1-yl)methyl]-5-sulfamoyl-benzamide

Conditions	Yield
In methanol at 110℃; for 20h;	74.4%

methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2) + homo-Lupinylamine → 5-Aminosulfonyl-2-methoxy-N-[2-(1α-quinolizidinyl)ethyl]-benzamide

Conditions	Yield
In methanol at 110℃; for 24h;	64%

3-(3,4-dichlorobenzylthio)thiophene-2-carboxylic acid (251096-84-1) + methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2) → methyl 5-(N-(3-(3,4-dichlorobenzylthio)thiophene-2-carbonyl)sulfamoyl)-2-methoxybenzoate (1336982-58-1)

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 25℃; for 6h; Inert atmosphere;	23%

methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2) + (+/-)-epilupinamine (2346-98-7, 10248-19-8, 15527-89-6, 22342-32-1, 46000-58-2, 75532-84-2, 145842-67-7) → 5-Aminosulfonyl-N-(1-epi-lupinyl)-2-methoxybenzamide

Conditions	Yield
In methanol at 110℃; for 24h; Yield given;

methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2) → N-benzyl-5-(aminosulfonyl)-2-methoxybenzamide (113681-63-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 98 percent / H2SO4 / 12 h / Heating 2: 5 percent / sodium methoxide / 5 h / 100 °C View Scheme

methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2) → N-(1-methyl-4-piperidinyl)-5-(aminosulfonyl)-2-methoxybenzamide (113681-64-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 98 percent / H2SO4 / 12 h / Heating 2: 54 percent / NaH / 1.) 100 deg C, 5 h; 2.) 120-130 deg C, 6 h View Scheme

1-cyclopentyl 2-aminomethyl pyrrolidine + methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2) → benzamide (55-21-0)

Conditions	Yield
In water; ethylene glycol; acetic acid

methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2) → 3-(Hydroxymethyl)-4-methoxybenzenesulfonamide (900165-91-5)

Conditions	Yield
With lithium borohydride In tetrahydrofuran; methanol at 20℃; for 8h;

methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2) → dimethyl 2-(2-(N-acetylsulfamoyl)-5-methoxy-4-(methoxycarbonyl)phenyl)malonate

Conditions	Yield
Multi-step reaction with 2 steps 1: zinc(II) chloride / 20 °C 2: silver(I) acetate; dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer / 1,2-dichloro-ethane / 5 h / 60 °C / Sealed tube View Scheme

Upstream product

• 67-56-1 methanol 
• 22117-85-7 2-methoxy-5-sulfamoylbenzoic acid 
• 33924-48-0 methyl 5-chloro-2-methoxybenzoate 
• 22117-84-6 3-cyano-4-methoxybenzenesulfonamide 

Downstream Products

• 15676-16-1 N-[(1-ethyl-2-pyrrolidinyl)methyl]-2-methoxy-5-sulfamoylbenzamide 
• 33045-53-3 2-methoxy-5-sulfamoylbenzoic acid ethyl ester 
• 177027-05-3 2-Methoxy-N-[(1S,9aR)-1-(octahydro-quinolizin-1-yl)methyl]-5-sulfamoyl-benzamide 
• 177027-05-3 5-Aminosulfonyl-N-(1-epi-lupinyl)-2-methoxybenzamide 
• 113681-63-3 N-benzyl-5-(aminosulfonyl)-2-methoxybenzamide 
• 113681-64-4 N-(1-methyl-4-piperidinyl)-5-(aminosulfonyl)-2-methoxybenzamide 
• 22117-85-7 2-methoxy-5-sulfamoylbenzoic acid 
• 55-21-0 benzamide 
• 900165-91-5 3-(Hydroxymethyl)-4-methoxybenzenesulfonamide 
• 15676-16-1 (S)-(-)-sulpiride 
• 1336982-58-1 methyl 5-(N-(3-(3,4-dichlorobenzylthio)thiophene-2-carbonyl)sulfamoyl)-2-methoxybenzoate 

Relevant academic research and scientific papers

Preparation method of 2-methoxy-5-sulfamoylbenzoic acid

The invention provides a preparation method of 2-methoxy-5-sulfamoylbenzoic acid, comprising the following steps: carrying out bromination reaction on 4-methoxybenzenesulfonamide and bromine under theaction of a reducing agent to obtain 3-bromo-4-methoxybenzenesulfonamide; carrying out substitution reaction on 3-bromo-4-methoxybenzenesulfonamide and cuprous cyanide under the action of a catalystto generate 3-cyano-4-methoxybenzenesulfonamide; carrying out alcoholysis on the 3-cyano-4-methoxybenzenesulfonamide and methanol under the catalysis of an acid to obtain 2-methoxy-5-sulfonamide methyl benzoate; hydrolyzing 2-methoxy-5-sulfonamide methyl benzoate under an alkaline condition, and then acidifying to obtain the 2-methoxy-5-sulfamoylbenzoic acid. The preparation method of the 2-methoxy-5-sulfamoylbenzoic acid is mild in reaction condition, simple in process and equipment, convenient to operate and environmentally friendly.

Preparation method of methyl 2-methoxy-5-sulfamoylbenzoate

The invention provides a preparation method of methyl 2-methoxy-5-sulfamoylbenzoate. The preparation method comprises the following steps: 2-methoxy-5-methyl chlorobenzoate and sodium amino sulfinate in a mole ratio being 1: (1.05-1.2) as well as a solvent and a catalyst are added to a reactor and react for 10-14 h when the temperature is controlled to be 45-60 DEG C; after reaction, activated carbon is added for decoloration, and the activated carbon, the catalyst and a by-product sodium chloride are removed through filtering; a filtrate is subjected to reduced-pressure concentration, and methyl 2-methoxy-5-sulfamoylbenzoate is obtained. The preparation method of methyl 2-methoxy-5-sulfamoylbenzoate has the advantages that an original process is short, the yield is high, the quality is good, three wastes contaminating the environment are avoided, environmental protection is realized, and the method is suitable for large-scale industrial production.

Method for conveniently synthesizing 2-methoxy-5-sulfamoyl methyl benzoate

The invention provides a method for conveniently synthesizing 2-methoxy-5-sulfamoyl methyl benzoate. The method comprises the following steps: adding 2-methoxyl-5-chloro methyl benzoate and sodium aminosulfinic acid in a molar ratio of 1: (1 to 1.1) as well as a solvent and a catalyst into a reaction device, controlling the temperature at 40 to 65 DEG C, and reacting for 12 to 18 hours; after the reaction is ended, adding activated carbon to perform decoloring, and filtering to remove the activated carbon, catalyst and side product sodium chloride; decompressing and concentrating filtrate to obtain the 2-methoxy-5-sulfamoyl methyl benzoate. The method for conveniently synthesizing the 2-methoxy-5-sulfamoyl methyl benzoate has the advantages that the technical flow is short, the yield is high, the quality is good, the three wastes (waste gas, waste water and industrial residue) polluting the environment are avoided, and the method is environment-friendly and suitable for the industrialized mass production.

Synthesis method of 2-methoxyl-5-amino sulfanoylmethyl benzoate

The invention provides a synthesis method of 2-methoxyl-5-amino sulfanoyl methyl benzoate. The synthesis method comprises the following steps: adding 2-methoxyl-5-chloromethyl benzoate, amino sodium sulfinate, a solvent and a catalyst into a reaction device; controlling the temprature to be 40 DEG C to 65 DEG C to react for 8 to 16 hours; after the reaction is finished, adding active carbon for de-coloring; filtering to remove the active carbon, the catalyst and a byproduct sodium chloride; concentrating under reduced pressure a filtrate to obtain the 2-methoxyl-5-sulfamoyl methyl benzoate. The synthesis method of the 2-methoxyl-5-sulfamoyl methyl benzoate, provided by the invention, has the advantages of short original technological process, high yield and good quality, has no three wastes which pollute the environment, is very environmental friendly, and is suitable for large-scale industrial production.

Method for synthesizing 2-methoxy-5-sulfamoylmethyl benzoate

The invention provides a method for synthesizing 2-methoxy-5-sulfamoyl methyl benzoate. The method comprises the following steps: adding 2-methoxy-5-chlorobenzene methyl formate and sodium aminosulfinate at the mol ratio of 1:1.05-1.2 and a solvent and a catalyst into a reactor, controlling temperature at 40-65 DEG C and reacting for 8-16 h; carrying out decoloration by adding active carbon after the reaction, filtering to remove active carbon, the catalyst and a by-product sodium chloride; and carrying out vacuum concentration on a filtrate so as to obtain 2-methoxy-5-sulfamoyl methyl benzoate. The method for synthesizing 2-methoxy-5-sulfamoyl methyl benzoate has advantages of short original process flow, high yield and good quality. In addition, ''three wastes (waste gas, waste water and industrial residue)'' which pollute the environment are not generated. The method is very environmentally friendly and is suitable for large-scale industrial production.

Method for synthesizing 2-methoxy-5-aminosulfonylmethyl benzoate by one-step method

The invention provides a method for synthesizing 2-methoxy-5-aminosulfonylmethyl benzoate by a one-step method. The method is characterized by adding 2-methoxy-5-methyl chlorobenzoate, sodium amino sulfonate, a solvent and a catalyst to a reaction device and controlling the temperature at 45-60 DEG C to react for 8-16 hours; adding activated carbon for decoloration after reaction is completed and removing activated carbon, the catalyst and a byproduct sodium chloride through filtration; carrying out vacuum concentration on the filtrate, thus obtaining 2-methoxy-5-aminosulfonylmethyl benzoate, wherein the mole ratio of 2-methoxy-5-methyl chlorobenzoate to sodium amino sulfonate is 1 to (1-1.1). The method for synthesizing 2-methoxy-5-aminosulfonylmethyl benzoate by the one-step method has the advantages that the original technological process is short; the yield is high; the quality is good; no three wastes polluting the environment are generated, so that the method is very environment-friendly and is suitable for large-scale industrial production.

Method for preparing 2-methoxy-5-sulfamoyl methyl benzoate

The invention provides a method for preparing 2-methoxy-5-sulfamoyl methyl benzoate. The method comprises the following steps: adding 2-methoxy-5-chlorobenzene methyl formate and sodium aminosulfinate at the mol ratio of 1:1-1.1 and a solvent and a catalyst into a reactor, controlling temperature at 40-65 DEG C and reacting for 8-16 h; carrying out decoloration by adding active carbon after the reaction, filtering to remove active carbon, the catalyst and a by-product sodium chloride; and carrying out vacuum concentration on a filtrate so as to obtain 2-methoxy-5-sulfamoyl methyl benzoate. The method for preparing 2-methoxy-5-sulfamoyl methyl benzoate has advantages of short original process flow, high yield and good quality. In addition, ''three wastes (waste gas, waste water and industrial residue)'' which pollute the environment are not generated. The method is very environmentally friendly and is suitable for large-scale industrial production.

Synthesis and preliminary pharmacological investigation of N-lupinyl-2-methoxybenzamides

A set of eleven N-lupinyl-2-methoxybenzamides, variously substituted on the benzene ring, together with two related compounds, were prepared and subjected to a large pharmacological screening, though not all compounds were tested in each assay. Compounds 1-10 displaced [125I]iodosulpride from D2 receptors only at very high concentration (IC50 > 5μM). At micromolar concentrations, compounds 1, 12, and 13 inhibited the binding of [3H]-pirenzepine and of [3H]-di-o-tolylguanidine respectively on M1 and sigma receptors; in the last case comp. 13 was more active (IC50 = 0.3 μM) than the epimeric 1. Compounds 1-10 at 10-25 mg/kg p.o. protected mice against electroshock induced seizures; l-sulpiride was inactive in this test. Compound 1 exhibited in three tests antiarrhythmic activity superior to that of quinidine and lidocaine. The same antagonized, in vitro, guinea pig ileum contractile response induced by several agents, and enhanced the intestinal transit rate in mice (charcoal bolus test). The last activity (shown in lower degree also by comp. 5) could be related to agonism with 5HT4 receptors, as could be expected for orthopramides with conformationally restricted side chains. This possibility is presently under investigation.