71675-85-9

Basic information

• Product Name: Amisulpride
• Synonyms: Sulamid;DAN-2163, Deniban, 4-Amino-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-(ethylsulfonyl)-2-methoxybenzamide;Benzamide, 4-amino-N-((1-ethyl-2-pyrrolidinyl)methyl)-5-(ethylsulfonyl)-2-methoxy-;4-Amino-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-(ethylsulfonyl)-2-benzamide;4-aMino-5-(ethanesulfonyl)-N-{[(2S)-1-ethylpyrrolidin-2-yl]Methyl}-2-MethoxybenzaMide;AMisulpride(DAN 2163);4-amino-N-((1-ethylpyrrolidin-2-yl)methyl)-5-(ethylsulfonyl)-2-methoxybenzamide;Amisulpride for system suitability
• CAS NO: 71675-85-9
• Molecular Formula: C₁₇H₂₇N₃O₄S
• Molecular Weight: 369.48
• EINECS: 275-831-7
• Product Categories: Active Pharmaceutical Ingredients;Antipsychotic;Drug Analogues;Intermediates & Fine Chemicals;Pharmaceuticals;Dopamine receptor;DENIBAN
• Mol File: 71675-85-9.mol

Chemical Properties

• Melting Point: 124-128
• Boiling Point: 558.9 °C at 760 mmHg
• Flash Point: 291.8 °C
• Appearance: white/solid
• Density: 1.2 g/cm³
• Vapor Pressure: 1.59E-12mmHg at 25°C
• Refractive Index: 1.545
• Storage Temp.: 2-8°C
• Solubility: DMSO: ≥5 mg/mL
• PKA: 13.73±0.46(Predicted)
• Merck: 14,485
• CAS DataBase Reference: Amisulpride(CAS DataBase Reference)
• NIST Chemistry Reference: Amisulpride(71675-85-9)
• EPA Substance Registry System: Amisulpride(71675-85-9)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• Safety Statements: 22-24/25
• WGK Germany: 3
• RTECS: CV2308701
• Hazardous Substances Data: 71675-85-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Amisulpride is used as a neuroleptic agent for its antipsychotic properties. It functions as a dopamine receptor antagonist, which helps in managing the symptoms of schizophrenia.
Used in Mental Health Treatment:
Amisulpride is used as an antipsychotic medication to treat the positive and negative symptoms of schizophrenia. Its dopamine receptor antagonist activity aids in controlling the hallucinations, delusions, and disorganized thoughts associated with the condition.

Originator

SESIF (Delagrange) (France)

Manufacturing Process

2-Methoxy-4-amino-5-ethylthiobenzoic acid: 159 g of 2-methoxy-4-amino-5-mercaptobenzoic acid, 355 ml of water and 160 ml of caustic soda solution are placed in a flask fitted with a condenser. The mixture is heated until the solid dissolves, then 123 g of ethyl sulfate is added. The mixture is heated to reflux, treated with 10 ml of 30% caustic soda solution, then heated to reflux for 1 hour. After cooling, 800 ml of water is added and the solution is filtered. The precipitate obtained by adding 100 ml of concentrated hydrochloric acid in the presence of ether is drained, washed with water and dried. 162 g of 2-methoxy-4-amino-5-ethylthiobenzoic acid is obtained (yield=88%). 2-Methoxy-4-amino-5-ethylsulfonylbenzoic acid: 123 g of 2-methoxy-4-amino-5-ethylthiobenzoic acid is dissolved hot in 542 ml of acetic acid. The solution obtained is cooled to 35°C, then 185 ml of hydrogen peroxide is added in small quantities while the temperature is raised to 80°C. The temperature is lowered to 40°C and the mixture is kept at that temperature for some hours and then cooled to 10°C. The precipitate formed is drained, washed with acetic acid and dried, then dissolved in 600 ml of water and 100 ml of 20% ammonia. The precipitate formed by adding 70 ml of concentrated hydrochloric acid is cooled, drained, washed with water and dried. 61.5 g of 2-methoxy-4-amino-5-ethylsulfonylbenzoic acid is obtained (yield 42%, M.P. 95-100°C). 4-Amino-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-(ethylsulfonyl)-2- methoxybenzamide: 81 g of 2-methoxy-4-amino-5-ethylsulphonylbenzoic acid and 297 ml of acetone are placed in a flask fitted with an agitator, a thermometer and a dropping funnel, followed by 33 g of triethylamine. The solution is cooled to 0°C, then 30 g of ethyl chloroformate is added drop by drop between 0° and 5°C. When the mixture has been agitated 51 g of 1-ethyl-2- aminomethylpyrrolidine is added drop by drop between 5° and 10°C. The mixture is agitated at 10°C then at ambient temperature. The triethylamine hydrochloride which precipitates is drained, then the acetone is distilled. The residue is dissolved in 600 ml of water in the presence of caustic soda solution. The base crystallizes after seeding and is drained, washed with water and dried. When the crystals have been purified by passing them through hydrochloride and recrystallising them in acetone, 66 g of 4-amino-N-[(1- ethyl-2-pyrrolidinyl)methyl]-5-(ethylsulfonyl)-2-methoxybenzamideis obtained (yield 61%, M.P. 126-127°C).

Therapeutic Function

Antipsychotic

Biological Activity

Potent, selective dopamine D 2 and D 3 receptor antagonist. K i values are 2.8 and 3.2 nM respectively for human D 2 and D 3 and > 1000 nM for human D 1 , D 4 and D 5 receptors. Shows selectivity for presynaptic dopamine autoreceptors at low doses and blocks postsynaptic D 2 /D 3 receptors at higher doses. Preferentially interacts with limbic D 2 -like receptors in vivo . Atypical antipsychotic/antischizophrenic agent with limited extrapyrimidal side effects and a profile distinct from that of haloperidol and remoxipride.

Biochem/physiol Actions

Amisulpride is a highly selective D2/D3 dopamine receptor antagonist and atypical antipsychotic.

Clinical Use

Treatment of acute and chronic schizophrenia

Drug interactions

Potentially hazardous interactions with other drugs Alcohol: may enhance CNS effects of alcohol. Anaesthetics: enhanced hypotensive effect. Analgesics: increased risk of convulsions with tramadol; enhanced hypotensive and sedative effects with opioids; increased risk of ventricular arrhythmias with methadone - avoid. Anti-arrhythmics: increased risk of ventricular arrhythmias with anti-arrhythmics that prolong the QT interval; avoid with amiodarone, disopyramide and procainamide (risk of ventricular arrhythmias). Antibacterials: avoid with erythromycin (increased risk of ventricular arrhythmias). Antidepressants: increased level of tricyclics. Antiepileptics: antagonises anticonvulsant effect. Antihypertensives: increased risk of hypotension. Antimalarials: avoid with artemether/lumefantrine. Antipsychotics: increased risk of ventricular arrhythmias with droperidol, sertindole - avoid. Antivirals: concentration possibly increased by ritonavir. Anxiolytics and hypnotics: increased sedative effects. Atomoxetine: increased risk of ventricular arrhythmias. Beta-blockers: increased risk of ventricular arrhythmias with sotalol. Cytotoxics: increased risk of ventricular arrhythmias with vandetanib - avoid; increased risk of ventricular arrhythmias with arsenic trioxide. Diuretics: increased risk of ventricular arrhythmias due to hypokalaemia. Pentamidine: increased risk of ventricular arrhythmias - avoid.

Metabolism

Amisulpride is weakly metabolised: two inactive metabolites, accounting for approximately 4% of the dose, have been identified. Amisulpride is eliminated unchanged in the urine. Fifty percent of an intravenous dose is excreted via the urine, of which 90% is eliminated in the first 24 hours.

references

[1] schoemaker h1, claustre y, fage d, rouquier l, chergui k, curet o, oblin a, gonon f, carter c, benavides j, scatton b. neurochemical characteristics of amisulpride, an atypical dopamine d2/d3 receptor antagonist with both presynaptic and limbic selectivity. j pharmacol exp ther. 1997 jan;280(1):83-97.

InChI:InChI=1/C17H27N3O4S/c1-4-20-8-6-7-12(20)11-19-17(21)13-9-16(25(22,23)5-2)14(18)10-15(13)24-3/h9-10,12H,4-8,11,18H2,1-3H3,(H,19,21)

Synthetic route

1-ethyl-2-pyrrolidinemethanamine (26116-12-1) + chloroformic acid ethyl ester (541-41-3) → amisulpride (71675-85-9)

Conditions	Yield
In triethylamine; acetone	100%
In triethylamine; acetone	84%

1-ethyl-2-pyrrolidinemethanamine (26116-12-1) + methyl 4-amino-5-(ethylsulfonyl)-2-methoxybenzoate → amisulpride (71675-85-9)

Conditions	Yield
With potassium tert-butylate In tert-butyl alcohol at 83℃; for 20h; Reagent/catalyst; Solvent; Temperature;	96.5%

1-ethyl-2-pyrrolidinemethanamine (26116-12-1) + 2-methoxy-4-amino-5-ethanesulfonylbenzoyl chloride → amisulpride (71675-85-9)

Conditions	Yield
In dichloromethane at 20 - 40℃; for 6h; Temperature;	89.4%

1-ethyl-2-pyrrolidinemethanamine (26116-12-1) + 2-methoxy-4-amino-5-ethylsulphonyl benzoic acid (71675-87-1) → amisulpride (71675-85-9)

Conditions	Yield
Stage #1: 2-methoxy-4-amino-5-ethylsulphonyl benzoic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 10 - 20℃; for 1.5h; Stage #2: 1-ethyl-2-pyrrolidinemethanamine With triethylamine In acetonitrile at 80℃; for 2h;	86.8%
With C36H24B4N2O3 In toluene for 14h; Molecular sieve; Reflux; chemoselective reaction;	76%
With chloroformic acid ethyl ester; triethylamine In acetone at 0 - 30℃;	70%

1-ethyl-2-pyrrolidinemethanamine (26116-12-1) + 2-methoxy-4-amino-5-ethylsulphonyl benzoic acid (71675-87-1) + chloroformic acid ethyl ester (541-41-3) → amisulpride (71675-85-9)

Conditions	Yield
With triethylamine In water; acetone	61%

ethyl bromide (74-96-4) + 4-amino-N-(1-ethyl-pyrrolidin-2-ylmethyl)-5-iodo-2-methoxy-benzamide (176849-91-5) → amisulpride (71675-85-9)

Conditions

Yield

Stage #1: ethyl bromide; 4-amino-N-(1-ethyl-pyrrolidin-2-ylmethyl)-5-iodo-2-methoxy-benzamide With 1,1'-bis-(diphenylphosphino)ferrocene; sodium metabisulfite; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; tin; potassium hydrogenphosphate trihydrate; tetrabutylammomium bromide In dimethyl sulfoxide at 100℃; for 10h; Inert atmosphere; Schlenk technique; Stage #2: With potassium carbonate In methanol at 20℃; for 2h;

61%

ethyl bromide (74-96-4) + C19H29N3O5S → amisulpride (71675-85-9)

Conditions	Yield
Stage #1: ethyl bromide; C19H29N3O5S With 1,1'-bis-(diphenylphosphino)ferrocene; sodium metabisulfite; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; tin; potassium hydrogenphosphate trihydrate; tetrabutylammomium bromide In dimethyl sulfoxide at 100℃; for 10h; Inert atmosphere; Stage #2: With potassium carbonate In methanol at 20℃; for 2h;	61%

2-methoxy-4-amino-5-ethylsulphonyl benzoic acid (71675-87-1) + 1-ethyl-2-aminomethylpyrrolidine hydrochloride → amisulpride (71675-85-9)

Conditions	Yield
Stage #1: 2-methoxy-4-amino-5-ethylsulphonyl benzoic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0℃; for 0.5h; Stage #2: 1-ethyl-2-aminomethylpyrrolidine hydrochloride With triethylamine In dichloromethane at 20℃;	29.7%

Methyl 4-amino-2-methoxybenzoate (27492-84-8) → amisulpride (71675-85-9)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: bromine / methanol / 5 - 15 °C / Industry scale 2.1: sodium sulfide / water; acetone / 5 - 15 °C / Industry scale 3.1: sodium hydroxide; water / methanol / 65 °C / Industry scale 3.2: 5 - 10 °C / pH 4 - 4.5 / Industry scale 4.1: dihydrogen peroxide / sodium tungstate / water; methanol / 5 h / 20 - 30 °C 5.1: chloroformic acid ethyl ester; triethylamine / acetone / 0 - 30 °C View Scheme
Multi-step reaction with 4 steps 1.1: bromine / methanol / 5 - 15 °C / Industry scale 2.1: sodium sulfide / water; acetone / 5 - 15 °C / Industry scale 3.1: dihydrogen peroxide / sodium tungstate / isopropyl alcohol / 40 - 45 °C / Industry scale 3.2: 60 - 65 °C / Industry scale 3.3: pH 4 - 4.5 / Industry scale 4.1: chloroformic acid ethyl ester; triethylamine / acetone / 0 - 30 °C View Scheme

4-Aminosalicylic acid (65-49-6) → amisulpride (71675-85-9)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: potassium hydroxide; tetrabutylammomium bromide / acetone / 1 h / 25 - 35 °C / Industry scale 2.1: bromine / methanol / 5 - 15 °C / Industry scale 3.1: sodium sulfide / water; acetone / 5 - 15 °C / Industry scale 4.1: sodium hydroxide; water / methanol / 65 °C / Industry scale 4.2: 5 - 10 °C / pH 4 - 4.5 / Industry scale 5.1: dihydrogen peroxide / sodium tungstate / water; methanol / 5 h / 20 - 30 °C 6.1: chloroformic acid ethyl ester; triethylamine / acetone / 0 - 30 °C View Scheme
Multi-step reaction with 5 steps 1.1: potassium hydroxide; tetrabutylammomium bromide / acetone / 1 h / 25 - 35 °C / Industry scale 2.1: bromine / methanol / 5 - 15 °C / Industry scale 3.1: sodium sulfide / water; acetone / 5 - 15 °C / Industry scale 4.1: dihydrogen peroxide / sodium tungstate / isopropyl alcohol / 40 - 45 °C / Industry scale 4.2: 60 - 65 °C / Industry scale 4.3: pH 4 - 4.5 / Industry scale 5.1: chloroformic acid ethyl ester; triethylamine / acetone / 0 - 30 °C View Scheme

methyl 4-amino-2-methoxy-5-thiocyanatobenzoate (59168-56-8) → amisulpride (71675-85-9)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: sodium sulfide / water; acetone / 5 - 15 °C / Industry scale 2.1: sodium hydroxide; water / methanol / 65 °C / Industry scale 2.2: 5 - 10 °C / pH 4 - 4.5 / Industry scale 3.1: dihydrogen peroxide / sodium tungstate / water; methanol / 5 h / 20 - 30 °C 4.1: chloroformic acid ethyl ester; triethylamine / acetone / 0 - 30 °C View Scheme
Multi-step reaction with 3 steps 1.1: sodium sulfide / water; acetone / 5 - 15 °C / Industry scale 2.1: dihydrogen peroxide / sodium tungstate / isopropyl alcohol / 40 - 45 °C / Industry scale 2.2: 60 - 65 °C / Industry scale 2.3: pH 4 - 4.5 / Industry scale 3.1: chloroformic acid ethyl ester; triethylamine / acetone / 0 - 30 °C View Scheme

2-methoxy-4-amino-5-ethylthio benzoic acid → amisulpride (71675-85-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: dihydrogen peroxide / sodium tungstate / water; methanol / 5 h / 20 - 30 °C 2: chloroformic acid ethyl ester; triethylamine / acetone / 0 - 30 °C View Scheme

methyl 4-amino-5-(ethylthio)-2-methoxybenzoate (1119455-01-4) → amisulpride (71675-85-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium hydroxide; water / methanol / 65 °C / Industry scale 1.2: 5 - 10 °C / pH 4 - 4.5 / Industry scale 2.1: dihydrogen peroxide / sodium tungstate / water; methanol / 5 h / 20 - 30 °C 3.1: chloroformic acid ethyl ester; triethylamine / acetone / 0 - 30 °C View Scheme

formic acid (64-18-6) + amisulpride (71675-85-9) → 4-formylamino-N-((1-ethyl-2-pyrrolidinyl)methyl)-5-(ethylsulfonyl)-2-methoxybenzamide

Conditions	Yield
With acetic anhydride at 5 - 20℃;	83%

Di-p-toluoyl-L-tartaric acid (32634-66-5) + amisulpride (71675-85-9) → (S)-4-amino-N-((1-ethylpyrrolidin-2-yl)methyl)-5-(ethylsulfonyl)-2-methoxybenzamide (2R,3R)-bis((4-methylbenzoyl)oxy)succinic acid salt

Conditions	Yield
In water; acetonitrile at 70℃; for 0.25h;	79.4%

amisulpride (71675-85-9) → (-)-Amisulpride

Conditions	Yield
With D-Malic acid In ethanol at 20℃; for 2h;	64.7%

amisulpride (71675-85-9) + cyclomaltooctaose (17465-86-0) → C48H80O40*C17H27N3O4S

Conditions	Yield
In methanol; water for 24h;

acetic acid (64-19-7) + amisulpride (71675-85-9) → 4-ethylamino-N-((1-ethyl-2-pyrrolidinyl)methyl)-5-(ethylsulfonyl)-2-methoxybenzamide

Conditions	Yield
With sodium tris(acetoxy)borohydride In 1,2-dichloro-ethane at 20℃;	309 mg

acetone (67-64-1) + amisulpride (71675-85-9) → 4-isopropylamino-N-((1-ethyl-2-pyrrolidinyl)methyl)-5-(ethylsulfonyl)-2-methoxybenzamide

Conditions	Yield
With sodium tris(acetoxy)borohydride; trifluoroacetic acid In N,N-dimethyl-formamide; acetone at 40℃; Cooling with ice;	550 mg

propionaldehyde (123-38-6) + amisulpride (71675-85-9) → 4-n-propylamino-N-((1-ethyl-2-pyrrolidinyl)methyl)-5-(ethylsulfonyl)-2-methoxybenzamide

Conditions	Yield
With sodium tris(acetoxy)borohydride In 1,2-dichloro-ethane	518 mg

benzaldehyde (100-52-7) + amisulpride (71675-85-9) → 4-benzylamino-N-((1-ethyl-2-pyrrolidinyl)methyl)-5-(ethylsulfonyl)-2-methoxybenzamide

Conditions	Yield
With sodium tris(acetoxy)borohydride; trifluoroacetic acid In N,N-dimethyl-formamide at 40℃;	366 mg

amisulpride (71675-85-9) → 4-dimethylamino-N-((1-ethyl-2-pyrrolidinyl)methyl)-5-(ethylsulfonyl)-2-methoxybenzamide

Conditions	Yield
Multi-step reaction with 3 steps 1: acetic anhydride / 5 - 20 °C 2: dimethylsulfide borane complex / tetrahydrofuran / 3 h / 5 - 60 °C 3: 21 h / 30 °C View Scheme

amisulpride (71675-85-9) → 4-ethylmethylamino-N-((1-ethyl-2-pyrrolidinyl)methyl)-5-(ethylsulfonyl)-2-methoxybenzamide

Conditions	Yield
Multi-step reaction with 3 steps 1: acetic anhydride / 5 - 20 °C 2: dimethylsulfide borane complex / tetrahydrofuran / 3 h / 5 - 60 °C 3: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 17 h / 20 °C View Scheme

amisulpride (71675-85-9) → 4-methylamino-N-((1-ethyl-2-pyrrolidinyl)methyl)-5-(ethylsulfonyl)-2-methoxybenzamide

Conditions	Yield
Multi-step reaction with 2 steps 1: acetic anhydride / 5 - 20 °C 2: dimethylsulfide borane complex / tetrahydrofuran / 3 h / 5 - 60 °C View Scheme

Eosin Y (548-26-5, 602-47-1, 17372-87-1) + amisulpride (71675-85-9) → C17H27N3O4S*C20H8Br4O5

Conditions	Yield
pH=3.3;

(2S,3S)-di-4-toluoyltartaric acid (32634-68-7) + amisulpride (71675-85-9) → (R)-(+)-4-amino-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-(ethylsulfonyl)-2-methoxybenzamide di-p-toluoyl tartrate

Conditions	Yield
In acetonitrile at 75℃; for 0.5h; Temperature; Inert atmosphere; Large scale;	26.73 kg

amisulpride (71675-85-9) → (-)-Amisulpride + (R)-(+)-4-amino-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-(ethylsulfonyl)-2-methoxybenzamide

Conditions	Yield
With diethylamine In acetonitrile at 30℃; under 26252.6 Torr; Resolution of racemate; Large scale;	A 3752.2 g B 2346 g

amisulpride (71675-85-9) → (R)-(+)-4-amino-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-(ethylsulfonyl)-2-methoxybenzamide

Conditions	Yield
Multi-step reaction with 2 steps 1: acetonitrile / 0.5 h / 75 °C / Inert atmosphere; Large scale 2: hydrogenchloride / water; tert-butyl methyl ether / 0.25 h / Inert atmosphere; Large scale View Scheme

amisulpride (71675-85-9) → (S)-(-)-4-amino-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-(ethylsulfonyl)-2-methoxybenzamide D-tartrate

Conditions	Yield
Multi-step reaction with 2 steps 1: diethylamine / acetonitrile / 30 °C / 26252.6 Torr / Resolution of racemate; Large scale 2: methanol / 0.75 h / 22 °C View Scheme

Upstream product

• 26116-12-1 1-ethyl-2-pyrrolidinemethanamine 
• 541-41-3 chloroformic acid ethyl ester 
• 71675-87-1 2-methoxy-4-amino-5-ethylsulphonyl benzoic acid 
• 27492-84-8 Methyl 4-amino-2-methoxybenzoate 
• 65-49-6 4-Aminosalicylic acid 
• 59168-56-8 methyl 4-amino-2-methoxy-5-thiocyanatobenzoate 
• 1119455-01-4 methyl 4-amino-5-(ethylthio)-2-methoxybenzoate 
• 74-96-4 ethyl bromide 
• 176849-91-5 4-amino-N-(1-ethyl-pyrrolidin-2-ylmethyl)-5-iodo-2-methoxy-benzamide 
• 80036-89-1 methyl 4-amino-5-(ethylsulfonyl)-2-methoxybenzoate 

Downstream Products

• 72005-57-3 (S)-(-)-4-amino-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-(ethylsulfonyl)-2-methoxybenzamide D-tartrate 
• 72005-57-3 (R)-(+)-4-amino-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-(ethylsulfonyl)-2-methoxybenzamide L-tartrate 

Relevant articles and documents

Preparation method of amisulpride

The invention relates to a preparation method of amisulpride, which comprises the steps of carrying out condensation reaction on 4-amino-2-methoxy-5-ethyl sulfonyl methyl benzoate, N-ethyl-2-aminomethylpyrrolidine and a solvent at the temperature of 50-100 DEG C under the condition of taking organic alkali as a catalyst, and after the reaction is finished, concentrating the reaction liquid to remove the solvent, and filtering and drying to obtain the amisulpride. The organic alkali is sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, sodium isopropoxide, potassium isopropoxide, potassium tert-butoxide or sodium tert-butoxide, and the specific synthetic route is shown in the description. By adopting the preparation method disclosed by the invention, a catalyst harmful to the environment is not used in the reaction process, the post-treatment is simple, the solvent is a common recyclable solvent, the yield reaches 90% or above, the purity can reach 99.7%, the single impurity content is less than 0.1%, the requirements of medicinal preparations are met, and the preparation method is suitable for industrial production.

Multicomponent Reductive Cross-Coupling of an Inorganic Sulfur Dioxide Surrogate: Straightforward Construction of Diversely Functionalized Sulfones

Conventionally, sulfones are prepared by oxidation of sulfides with strong oxidants. Now, a multicomponent reductive cross-coupling involving an inorganic salt (sodium metabisulfite) for the straightforward construction of sulfones is disclosed. Both intramolecular and intermolecular reductive cross-couplings were comprehensively explored, and diverse sulfones were accessible from the corresponding alkyl and aryl halides. Intramolecular cyclic sulfones were systematically obtained from five- to twelve-membered rings. Naturally occurring aliphatic systems, such as steroids, saccharides, and amino acids, were highly compatible with the SO2-insertion reductive cross-coupling. Four clinically applied drug molecules, which include multiple heteroatoms and functional groups with active hydrogens, were successfully prepared via a late-stage SO2 insertion. Mechanistic studies show that alkyl radicals and sulfonyl radicals were both involved as intermediates in this transformation.

(S)(-)-amisulpride preparation method

The invention relates to an (S)(-)-amisulpride preparation method, which comprises: carrying out condensation on 4-amino-5-(ethylsulfonyl)-2-methoxybenzoyl chloride and 1-ethyl-2-aminomethyl pyrrolidine to obtain amisulpride, and resolving the amisulpride by using D-malic acid to obtain (S)-(-)-amisulpride.

Aryl alkyl sulfone compound and reducing coupling method for constructing sulfone compounds

The invention discloses an aryl alkyl sulfone compound shown as a formula (1) and a synthetic method thereof. The aryl alkyl sulfone compound is prepared by taking an aromatic iodide, an inorganic sulfur reagent and an alkyl bromide as reaction raw materials to carry out reacting in a solvent under action of alkali, a catalyst, a ligand, a reducing agent and an additive. According to the invention, an inorganic sulfur reagent is used as a sulfur source to construct the aryl alkyl sulfone compound in one step under catalysis and reduction conditions, so that the defect in synthesizing the arylalkyl sulfone compound by conventional oxidation of thioether is avoided. The aryl alkyl sulfone compound developed by the invention can be used for synthesizing aryl alkyl sulfone medicines.

Preparation method of amisulpride

The invention provides a preparation method of amisulpride. The preparation method comprises the following steps: with 2-methoxy-4-amino-5-ethylsulfonyl benzoic acid and thionyl chloride as raw materials, carrying out an acylation reaction to obtain 2-methoxy-4-amino-5-ethylsulfonyl benzoyl chloride; and then, subjecting 2-methoxy-4-amino-5-ethylsulfonyl benzoyl chloride and N-ethyl-2-aminomethylpyrrolidine to an amidation reaction on to obtain amisulpride. The preparation method has the following advantages: raw materials are easy to obtain; highly toxic products are not used; the preparation method is simple; preparation period is short; side reactions are few; the yield and purity of the target product are high; and the target product has market competitiveness.

Unique physicochemical and catalytic properties dictated by the B3NO2 ring system

The expansion of molecular diversity beyond what nature can produce is a fundamental objective in chemical sciences. Despite the rich chemistry of boron-containing heterocycles, the 1,3-dioxa-5-aza-2,4,6-triborinane (DATB) ring system, which is characterized by a six-membered B3NO2 core, remains elusive. Here, we report the synthesis of m-terphenyl-templated DATB derivatives, displaying high stability and peculiar Lewis acidity arising from the three suitably arranged boron atoms. We identify a particular utility for DATB in the dehydrative amidation of carboxylic acids and amines, a reaction of high academic and industrial importance. The three boron sites are proposed to engage in substrate assembly, lowering the entropic cost of the transition state, in contrast with the operative mechanism of previously reported catalysts and amide coupling reagents. The distinct mechanistic pathway dictated by the DATB core will advance not only such amidations, but also other reactions driven by multisite activation.

AN IMPROVED PROCESS FOR PREPARATION OF AMISULPRIDE

The present invention is related to a novel process for the preparation of amisulpride (I) which involves : methylation of 4-amino-salicylic-acid (VI) with dimethyl sulphate and base, optionally in presence of TBAB to obtain 4-amino-2-methoxy methyl benzoate (VII) and (ii) oxidation of 4-amino-2-methoxy-5-ethyl thio benzoic acid (IX) or 4-amino-2-methoxy-5- ethyl thio methyl benzoate (X) with oxidizing agent in the presence of sodium tungstate or ammonium molybdate to give 2-methoxy-4-amino-5-ethyl-sulfonyl benzoic acid (IV) or 2- methoxy-4-amino-5-ethyl-sulfonyl methyl benzoate (XI) respectively.

SUBSTITUTED BENZAMIDE MODULATORS OF DOPAMINE RECEPTOR

The present invention relates to new substituted benzamide modulators of dopamine receptor, pharmaceutical compositions thereof, and methods of use thereof.

New derivatives of 4-amino-5-alkyl sulphonyl orthoanisamides, methods of preparing them and their application as psychotropic agents

There are provided certain N-(1-lower alkyl-2-pyrrolidylmethyl)2-lower aly-4-amino-5-lower alkyl sulphonyl benzamides and derivatives thereof which provide surprising antiapomorphine and antiserotonin activity.