71675-85-9 Hazards Identification
Pictogram(s):
Signal:
Warning
GHS Hazard Statements:
H302 (91.38%): Harmful if swallowed [Warning Acute toxicity, oral]
H312 (15.52%): Harmful in contact with skin [Warning Acute toxicity, dermal]
H315 (10.34%): Causes skin irritation [Warning Skin corrosion/irritation]
H319 (20.69%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]
H332 (15.52%): Harmful if inhaled [Warning Acute toxicity, inhalation]
H335 (20.69%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]
Precautionary Statement Codes:
P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P317, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501
Hazard Classes and Categories:
Acute Tox. 4 (91.38%)
Acute Tox. 4 (15.52%)
Skin Irrit. 2 (10.34%)
Eye Irrit. 2 (20.69%)
STOT SE 3 (20.69%)
71675-85-9 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.
Check Digit Verification of cas no
The CAS Registry Mumber 71675-85-9 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 7,1,6,7 and 5 respectively; the second part has 2 digits, 8 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 71675-85:
(7*7)+(6*1)+(5*6)+(4*7)+(3*5)+(2*8)+(1*5)=149
149 % 10 = 9
So 71675-85-9 is a valid CAS Registry Number.
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)
71675-85-9Relevant academic research and scientific papers
Preparation method of amisulpride
-
Paragraph 0034-0043, (2021/04/10)
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
Meng, Yingying,Wang, Ming,Jiang, Xuefeng
supporting information, p. 1346 - 1353 (2019/12/11)
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
-
Paragraph 0004, (2020/03/06)
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
-
Paragraph 0362-0366, (2019/12/25)
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
-
Paragraph 0039; 0042-0045; 0048-0049; 0052-0053; 0056; 0058, (2019/12/29)
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
Noda, Hidetoshi,Furutachi, Makoto,Asada, Yasuko,Shibasaki, Masakatsu,Kumagai, Naoya
, p. 571 - 577 (2017/06/01)
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
-
, (2012/01/06)
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
-
Page/Page column 12-13, (2010/05/13)
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
-
, (2008/06/13)
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.
