43200-80-2

43200-80-2 - Names and Identifiers

Name	Zopiclone
Synonyms	Amoban Amovane Imovane Sopivan Imovance RP-27267 zopiclone oxo-5h-pyrrolo(3,4-b)pyrazin-5-ylester 6-(5-Chloro-2-pyridinyl)-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-yl 4-methyl-1-piperazinecarboxylate 4-Methyl-1-piperazinecarboxylic acid 6-(5-chloro-2-pyridinyl)-6,7-dihydro-7-oxo-5H-pyrrolo[3,4-b]pyrazin-5-yl ester 4-({[(5S)-6-(5-chloropyridin-2-yl)-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-yl]oxy}carbonyl)-1-methylpiperazin-1-ium 4-Methyl-1-piperazinecarboxylic acid ester with 6-(5-chloro-2-pyridyl)-6,7-dihydro-7-hydroxy-5H-pyrrolo[3,4-b]pyrazin-5-one
CAS	43200-80-2
EINECS	256-138-9
InChI	InChI=1/C17H17ClN6O3/c1-22-6-8-23(9-7-22)17(26)27-16-14-13(19-4-5-20-14)15(25)24(16)12-3-2-11(18)10-21-12/h2-5,10,16H,6-9H2,1H3/p+1/t16-/m0/s1
InChIKey	GBBSUAFBMRNDJC-UHFFFAOYSA-N

43200-80-2 - Physico-chemical Properties

Molecular Formula	C17H17ClN6O3
Molar Mass	388.81
Density	1.1105 (estimate)
Melting Point	1780C
Boling Point	580.7±50.0 °C(Predicted)
Flash Point	2℃
Solubility	DMSO: 2mg/mL
Vapor Presure	1.78E-13mmHg at 25°C
pKa	pKa ﹣1.5±0.1(10% ACN inaq. H2SO4t = 25.0) (Uncertain)
Storage Condition	Store at RT
Physical and Chemical Properties	White to light yellow crystal or crystalline powder, odorless, bitter taste. Soluble in dimethyl sulfoxide or chloroform, more soluble in acetic acid, more difficult to dissolve in methanol, acetone or acetonitrile, very difficult to dissolve in ether or isopropanol, a few insoluble in water. Melting point 178 °c.
Use	Used as a sedative hypnotic

43200-80-2 - Risk and Safety

Risk Codes	R20/21/22 - Harmful by inhalation, in contact with skin and if swallowed. R36/37/38 - Irritating to eyes, respiratory system and skin. R62 - Possible risk of impaired fertility R36 - Irritating to the eyes R11 - Highly Flammable
Safety Description	S26 - In case of contact with eyes, rinse immediately with plenty of water and seek medical advice. S36 - Wear suitable protective clothing. S36/37 - Wear suitable protective clothing and gloves. S16 - Keep away from sources of ignition.
UN IDs	UN 1648 3 / PGII
WGK Germany	3
RTECS	TL1425000
HS Code	29339900

43200-80-2 - Standard

Authoritative Data Verified Data

This product is 6-(5-chloropyridin-2-yl)-7-[(4-methylpiperazin-1-yl) formyloxy]-5, 6-dihydropyrrolo [3,4-b] pyrazin-5-one. The content of C17H17C1NS03 shall not be less than 98.5% calculated as dried product.

Last Update：2024-01-02 23:10:35

43200-80-2 - Trait

Authoritative Data Verified Data

This product is a white to yellowish crystalline powder.
This product is soluble in dichloroethane, slightly soluble in methanol or N,N-dimethylformamide, slightly soluble in ethanol, almost insoluble in water; Slightly soluble in dilute hydrochloric acid.

melting point

The melting point of this product (General C612) is 175~178°C.

absorption coefficient

take this product, precision weighing, with O. 1 mol/L hydrochloric acid solution was dissolved and quantitatively diluted to prepare a solution containing 15ug per 1 ml, which was measured by UV-Vis spectrophotometry (General 0401), and the absorbance was measured at the wavelength of 303nm, the absorption coefficient is 345 to 380.

Last Update：2022-01-01 11:58:16

43200-80-2 - Differential diagnosis

Authoritative Data Verified Data

take about 10 mg of this product, add 5ml of dilute hydrochloric acid, shake to dissolve Zopiclone, and add about 3 drops of potassium iodide test solution to produce slightly milky yellow precipitate.
the solution under the term of absorption coefficient was taken and measured by ultraviolet-visible spectrophotometry (General rule 0401), and the maximum absorption was found at a wavelength of Nm.
The infrared absorption spectrum of this product should be consistent with that of the control (Spectrum set 755).

Last Update：2022-01-01 11:58:16

43200-80-2 - Exam

Authoritative Data Verified Data

clarity and color of solution

take 0.50g of this product and add 0902 of N,N-dimethylformamide to dissolve, the solution should be clear and colorless; If it is turbid, compare it with No. 2 Turbidity standard solution (General rule first method), should not be more concentrated; If the color, with the yellow 5 standard colorimetric liquid (General Principles 0901 first method), not deeper.

optical rotation

weigh 0.25g of this product accurately, put it in a 25ml measuring flask, add N ,N-dimethylformamide to dissolve and dilute to the scale, shake well, and measure it according to law (General rule 0621), the optical rotation is from 0.05 ° to +0.05 °.

chloride

take this product l. Add 50ml of water for ultrasound to dissolve, filter, take the filtrate 25.0, check according to law (General 0801), and standard sodium chloride solution 5.0ml of the control solution should not be more concentrated (0.01%).

Related substances

take about 10 mg of this product, put it in a 10ml measuring flask, add mobile phase ultrasound to dissolve Zopiclone and dilute to the scale, shake well, as a test solution; Take 1ml with precision, in a 200ml measuring flask, dilute to the scale with mobile phase, shake well, as a control solution; Take 1ml of the control solution precisely, put it in a 20ml measuring flask, dilute to the scale with mobile phase, shake well, as a sensitivity solution. Take about 10 mg of this product, put it in a 10ml measuring flask, add 2ml of methanol to dissolve, add 0.1ml of hydrogen peroxide, heat it in water bath for 15 minutes, let it cool, dilute it to the scale with mobile phase, shake it well, as a system suitability solution. According to the high performance liquid chromatography (General rule 0512) test, with the eighteen alkyl silane bonded gel as the filler (Agilent C18, mm x mm, 5um or equivalent performance column); with acetonitrile-phosphate solution (take sodium dodecyl sulfate 8.lg and sodium dihydrogen phosphate 1.6g, add water 1000ml to dissolve, adjust the pH value to 3.5 with phosphoric acid (37.5 : 62.5) as mobile phase; The detection wavelength is 303nmD, the mobile phase ratio is adjusted so that the retention time of the main component chromatographic peak is 27-31 minutes, and the separation degree between the main component peak and the impurity peak at the relative retention time of about 0.9 should meet the requirements. The number of theoretical plates is not less than 3000 calculated from the zopiclone peak. The sensitivity of the solution 20ul injection liquid chromatography, the signal to noise ratio of the main component peak height should be greater than 10. 20 u1 of test solution and 20 u1 of control solution were respectively injected into human liquid chromatograph, and the chromatogram was recorded to 1.5 times of the retention time of principal component peak. If there are impurity peaks in the chromatogram of the test solution, the area of a single impurity peak shall not be greater than 0.2 times (0.1%) the area of the main peak of the control solution, and the sum of the areas of each impurity peak shall not be greater than the area of the main peak of the control solution (0.5%). The chromatogram of the test solution is 0.1 times smaller than the main peak area of the control solution.

residual solvent

take about 0.5g of this product, weigh it accurately, put it in a 20ml headspace bottle, add 5ml of dimethyl sulfoxide accurately, seal it, shake it to dissolve it, and use it as a test solution; in addition, take three gas methane, dichloromethane, dioxane, ethanol, acetonitrile, isopropyl ether, pyridine and N ,N-dimethylformamide, respectively, prepare mixed solutions containing about 0.006mg, 0.06mg, 0.038mg, 0.5mg, 0.041mg, 0.5mg, 0.02mg and 0.088mg in 1 ml by quantitative dilution with dimethyl sulfinism, and take 5ml with precision, A 20ml headspace bottle was placed, sealed, and used as a control solution. Test as residual solvent assay (General 0861 second method). The capillary column with 6% cyanopropylphenyl-94% dimethylpolysiloxane (or similar polarity) as stationary liquid is used as the column; The initial temperature is 40°C, and the retention time is 8.5 minutes, the temperature is raised to 100°C at a rate of 5°C per minute and then to 200°C at a rate of 20°C per minute for 1 minute; The temperature of the sample inlet is 200°C; And the temperature of the detector is 250°C; the Headspace bottle equilibration temperature was 100°C and the equilibration time was 30 minutes. Take the reference solution into the headspace, the separation degree between the peaks of each component shall meet the requirements. Then the sample solution and the reference solution were injected with headspace, and the chromatogram was recorded. According to the external standard method, the residual amount of chloroform, dichloromethane, dioxane, ethanol, acetonitrile, isopropyl ether, pyridine and N,N-dimethylformamide shall comply with the regulations.

loss on drying

take this product, with phosphorus pentoxide as desiccant, at 60°C under reduced pressure drying to constant weight, weight loss should not exceed 0.5% (General rule 0831).

ignition residue

take l.Og of this product and check it according to law (General rule 0841). The residue left shall not exceed 0.1%.

Heavy metals

The residue left under the item of ignition residue shall not contain more than 20 parts per million of heavy metal when examined by law (General rule 0821).

Last Update：2022-01-01 11:58:17

43200-80-2 - Content determination

Authoritative Data Verified Data

take this product about 0.3g, precision weighing, add glacial acetic acid dissolved in 20ml, add crystal violet indicator liquid 1 drop, with high gas acid titration solution (0.1 mol/L) titration to a blue color of the solution, and the results of the titration were corrected by a blank test. Each 1 ml of perchloric acid titration solution (0.1 mol/L) corresponds to 38.88mg of C17H17C1N603.

Last Update：2022-01-01 11:58:18

43200-80-2 - Category

Authoritative Data Verified Data

hypnotic drugs.

Last Update：2022-01-01 11:58:18

43200-80-2 - Storage

Authoritative Data Verified Data

light shielding, sealed storage.

Last Update：2022-01-01 11:58:18

43200-80-2 - Zopiclone tablets

Authoritative Data Verified Data

This product contains zopiclone (C17H17C1NS03) should be 90.0% to 110.0% of the label.

trait

This product is a film-coated tablet, white or off-white after removal of the coating.

identification

take an appropriate amount of the fine powder of this product (about 1Omg of zopiclone), add 15ml of dilute hydrochloric acid, shake to dissolve the mixed clone, filter, add about 3 drops of potassium Mercury iodide test solution to the filtrate, that is, a slightly milky yellow precipitate was generated.
The test solution under the item of related substances was taken and diluted with the mobile phase under the item of related substances to contain 0.1 mg of solution, as the test solution; Take the appropriate amount of Zopiclone control, diluted with the mobile phase under the item of related substances to make 0. The lmg solution is used as the reference solution, and the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the reference solution according to the chromatographic conditions of the related substances.
the sample solution under the content measurement item was taken and measured by ultraviolet-visible spectrophotometry (General 0401), and there was a maximum absorption at a wavelength of Nm.

examination

Related substances appropriate amount of Zopiclone powder (about equivalent to Zopiclone lOmg) was added into a 10ml measuring flask, and zopiclone was dissolved and diluted to the scale by adding mobile phase ultrasound, take the filtrate as the test solution; Take 1ml of the precision volume, put it in a 200ml measuring flask, dilute it to the scale with mobile phase, shake it, and use it as the control solution; Take 1ml of the control solution with the precision volume, dilute to the scale with mobile phase, shake well, take about 10 mg zopiclone as a sensitive solution, put it in a 10ml measuring flask, add 2ml of methanol to dissolve, and add 0.1ml of hydrogen peroxide, the mixture was heated in a water bath for 15 minutes, allowed to cool, diluted to the scale with the mobile phase, and shaken to serve as a system-suitable solution. The determination was carried out according to the method of Zopiclone related substances. If there are impurity peaks in the chromatogram of the test solution, the area of a single impurity peak shall not be greater than the area of the main peak of the control solution (0.5% ), and the sum of each impurity peak area shall not be greater than 3 times the area of the main peak of the control solution (1.5%). The chromatogram of the test solution is 0.1 times smaller than the main peak area of the control solution.
dissolution of this product, according to the dissolution and release determination method (General 0931 third method), with 0.lmol/L hydrochloric acid solution 250tnl is the dissolution medium, the rotation speed is 50 revolutions per minute, the operation is carried out according to law, after 30 minutes, the solution is filtered, and the filtrate is taken, and 0.1 mol/L hydrochloric acid solution was diluted to prepare a solution containing about 15ug per 1 ml as a test solution, and the dissolution amount of each tablet was calculated according to the method under the content measurement item. The limit is 75% of the labeled amount and shall be in accordance with the provisions.
shall be calculated from the content of each tablet measured under the content determination item, and shall comply with the regulations (General rule 0941).
others shall be in accordance with the relevant provisions under the item of tablets (General rule 0101).

Content determination

Take 10 tablets of this product, respectively 0. The 1 mol/L hydrochloric acid solution was triturated in portions and transferred to a 50ml measuring flask with 0. Dilute the lmol/L hydrochloric acid solution to the scale, shake well, filter, take the appropriate amount of filtrate accurately, use 0.1 mol/L hydrochloric acid solution is made into a solution containing about 15ug per 1 ml, which is used as a test solution, and the absorbance is measured at the wavelength of 304nm by ultraviolet-visible spectrophotometry (General rule 0401); in addition, an appropriate amount of Zopiclone reference substance was accurately weighed and added with 0.1 mol/L hydrochloric acid solution was dissolved and quantitatively diluted to prepare a solution containing about 15ug per 1 ml, and the absorbance was measured by the same method. The content of each tablet was calculated, and the average content of 10 tablets was obtained.

specification

(1)3.75mg (2)7.5mg

storage

light shielding, sealed storage.

Last Update：2022-01-01 11:58:19

43200-80-2 - Zopiclone capsules

Authoritative Data Verified Data

This product contains zopiclone (C17H17C1NS03) should be 90.0% to 110.0% of the label.

trait

The content of this product is white or white particles.

identification

take an appropriate amount of the content of this product (about 10mg of zopiclone), add 5ml of dilute hydrochloric acid, shake to dissolve Zopiclone, filter, and add about 3 drops of potassium Mercury iodide test solution to the filtrate, resulting in slightly milky yellow precipitate.
The test solution under the item of related substances was taken and diluted with the mobile phase under the item of related substances to contain 0. The solution of lmg is used as the test solution; An appropriate amount of Zopiclone reference substance is taken and diluted with the mobile phase under the item of related substances to make a solution containing 0. The lmg solution is used as the reference solution, and the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the reference solution according to the chromatographic conditions of the related substances.
the sample solution under the content measurement item was taken and measured by ultraviolet-visible spectrophotometry (General 0401), and there was a maximum absorption at a wavelength of Nm.

examination

Related Substances: take an appropriate amount of the contents of this product (about equivalent to Zopiclone lOmg), put it in a 10ml measuring flask, add mobile phase ultrasound to dissolve Zopiclone and dilute to the scale, shake well, filter, take the continued filtrate as the test solution; Take 1ml of the precision volume, put it in a 200ml measuring flask, dilute it to the scale with the mobile phase, shake it, and use it as the control solution; Take 1ml of the precision control solution, in a 20ml measuring flask, dilute to the scale with the mobile phase, and shake to serve as a sensitivity solution. Take about 10mg of Zopiclone, put it in a 10ml measuring flask, add 2ml of methanol to dissolve it, add 0.1 mL of hydrogen peroxide, heat it in a water bath for 15 minutes, let it cool, dilute it to the scale with mobile phase, shake well, and use it as a system applicable solution. The determination was carried out according to the method of Zopiclone related substances. If there are impurity peaks in the chromatogram of the test solution, the area of a single impurity peak shall not be greater than 0.2 times (0.1%) the area of the main peak of the control solution, and the sum of the areas of each impurity peak shall not be greater than the area of the main peak of the control solution (0.5%). The chromatogram of the test solution is 0.1 times smaller than the main peak area of the control solution.
dissolution of this product, according to the dissolution and release determination method (General 0931 third method), with 0.1 mol/L hydrochloric acid solution 250ml as the dissolution medium, the rotation speed is 50 revolutions per minute, according to the operation, after 30 minutes, take the solution, filter, take the filtrate with 0.1 mol/L hydrochloric acid solution is made into a solution containing about 15ug per 1 ml, as a test solution; Another precision weighing Zopiclone control appropriate amount, with 0.1 mol/L hydrochloric acid solution was prepared as a control solution containing about 15ug per 1 ml. Take the test solution and the reference solution, according to the UV-visible spectrophotometry (General rule 0401), measure the absorbance at the wavelength of 304nm, calculate the dissolution amount of each particle, the limit is 80% of the labeled amount and shall be in accordance with the provisions.
shall be calculated based on the content of each particle measured under the content determination item, and shall comply with the regulations (General rule 0941).
others should comply with the relevant provisions under the capsule (General 0103).

Content determination

Take 10 capsules of this product, pour the contents into a 50ml measuring flask respectively, and use 0.1 mol/L hydrochloric acid solution was washed, the washing liquid was incorporated into the measuring flask, and 0.1 mol/L hydrochloric acid solution about 30ml, fully shake the zopiclone dissolved, with 0. Dilute the lmol/L hydrochloric acid solution to the scale, shake well, filter, take the appropriate amount of filtrate accurately, use 0.1 mol/L hydrochloric acid solution is made into a solution containing about 15ug per 1 ml, which is used as a test solution, and the absorbance is measured at 304mn wavelength by ultraviolet-visible spectrophotometry (General rule 0401); in addition, an appropriate amount of Zopiclone reference substance was accurately weighed and added with 0.1 mol/L hydrochloric acid solution was dissolved and quantitatively diluted to prepare a solution containing about 15ug per 1 ml. The absorbance was measured by the same method, the content of each particle was calculated, and the average content of 10 particles was obtained.

specification

3.75mg

storage

light shielding, sealed storage.

Last Update：2022-01-01 11:58:20

43200-80-2 - Reference Information

NIST chemical information	Information provided by: webbook.nist.gov (external link)
Hypnotics	The drug treatment of insomnia has gone through three short-acting drugs: barbiturates, benzodiazepines, and non-benzodiazepines. stage. Benzodiazepines are still the most widely used hypnotics. They are safe, fast-acting, and well-tolerated. Drugs with a longer half-life, but they are generally not suitable for the elderly to avoid accumulation and hangover. All benzodiazepine preparations have addiction and alcohol-like effects, and dependence is mainly seen in long-acting drugs. The benzodiazepine receptor (GABA) is composed of 2 α, 2 β and 1 γ subunit. Each subunit contains 4 transmembrane regions. The benzodiazepine recognition site is located in the α and After the ligand is combined with this site, the GABA recognition site at the interface of the α and β subunit is occupied by GABA, this changes the function of chlorine conductivity and promotes chloride ion inflow. There are two benzodiazepine receptor subtypes in the brain: receptor 1 and receptor 2. Most benzodiazepines act on these two receptors non-selectively, with both hypnotic effects and central nervous system side effects. Most clinical patients do not dare to use benzodiazepines because they know that benzodiazepines are addictive, so that they do not take the medicine according to the doctor's advice, resulting in irregular treatment. Zopiclone is a new generation of sedative and hypnotic non-benzodiazepine drugs. It has strong sedative, hypnotic and muscle relaxation effects. It has good sleep induction, reduces awakening and anxiety, and has no obvious withdrawal and rebound. It has no damage to memory and effectively improves the quality of sleep. It is an effective and safe non-benzodiazepine hypnotic for the treatment of sleep disorders and is worthy of recommendation. Zopiclone, also known as Yimenghui (Imovanee), was first marketed by a French Rhone-pouleen company in 1987. The drug is a pyrrolidone compound and is called the third-generation sleeping pill. Its mode of action is different from benzodiazepine sleeping pills. It can selectively inhibit the reuptake of serotonin in brain synapses, and also has antidepressant and anti-anxiety symptoms, it overcomes the shortcomings of barbiturates and second-generation benzodiazepines sedative hypnotics with large toxicity and side effects. It has a short half-life in the body (5 hours), a bioavailability of 80%,45% -80% and plasma proteins Combined and widely distributed throughout the body, liver metabolism, 80% excreted from the urine, only about 5% of unmetabolized drugs in the urine. Taking it before going to bed, the phenomenon of "hangover" is rarely produced in the next morning, and repeated use will not accumulate. It is especially suitable for patients with temporary difficulty falling asleep and early awakening. It has little inhibitory effect on the respiratory system and does not affect the mental activity and movement of the next morning. The sensitivity and side effects are minimal. The pharmacokinetic characteristics of hypnotics, especially the length of the elimination half-life, are important factors that determine the severity and incidence of adverse reactions. Zopiclone has a short action time and a fast concentration peak, which is equivalent to the commonly used estazolam. It can effectively improve the quality of sleep, no hangover after waking up the next day, good during the day, and no memory damage.
properties	white to light yellow crystalline powder, odorless, bitter, easily soluble in dimethyl sulfoxide or chloroform, more easily soluble in glacial acetic acid or anhydrous acetic acid, hardly soluble in methanol, acetonitrile, acetone or ethanol, extremely hardly soluble in ether or isopropanol, almost insoluble in water.
pharmacological effects	the conventional dose of this product has sedative, hypnotic and muscle relaxation effects. It acts on benzodiazepine receptors, but its binding method is different from benzodiazepine drugs. This product is a quick-acting hypnotic, which can prolong sleep time, improve sleep quality, and reduce the number of night awakenings and early awakenings. This product is characterized by low residual effect in the next morning. Fig. 1 is zopiclone
benzodiazepines (BZD) and non-benzodiazepines (BzRA) hypnotics	benzodiazepines (BZD) and non-benzodiazepines (BzRA) hypnotics: BZD drugs are the prototype of sleep-promoting drugs and have been used as the first choice for insomnia treatment. Traditional BZD drugs are combined with GABA benzodiazepine receptor subtypes BZ1, BZ2, BZ3, which are related to sedation and amnesia, anti-anxiety, ataxia and anti-epilepsy, respectively. However, BZD drugs are related to adverse reactions such as drug resistance, addiction, hangover and cognitive impairment, and can also lead to insomnia rebound. Sudden withdrawal of BZD drugs can cause anxiety, irritability and restlessness. In addition, it can also cause obstructive sleep asphyxia, especially in elderly patients. In recent years, with the development of BzRA, the range of sleep-promoting drugs has greatly increased. BzRA includes zolpidem (zolpidem), zaleplon (zaleplon), zopiclone (zopiclone) and dexzopiclone (esopiclone), also collectively referred to as "drug z". Unlike BZD drugs, BzRA selectively binds to BZ1 receptor to achieve a sleep-promoting effect, with few adverse reactions such as anxiety and ataxia. This product and BZD drugs have similar sleep-promoting effects, but rarely cause sleep rebound, drug resistance, withdrawal reaction and potential abuse or addiction, and rarely change the sleep structure, without muscle relaxation, anti-epilepsy and anti-anxiety effects. Potential adverse effects of BzRA include sleep behavior disorders, such as sleepiness, residual sedation, memory and daily function changes. At the same time, long-term use can lead to drug resistance, decreased efficacy, and even drug dependence.
pharmacokinetics	absorption: this product absorbs rapidly after oral administration, and the blood drug concentration peaks in 1.5-2 hours. after administration of 3.75, 7.5 and 15mg, it is 30, 60 and 115ng/ml respectively. Bioavailability is about 80%. Distribution: The drug is rapidly distributed throughout the body with a distribution volume of 100L/kg; The binding rate of plasma protein is low, about 45%. Metabolism: It is metabolized by cytochrome P450 enzyme in the liver. The main metabolites are N-oxide (with pharmacological activity) and N-demethyl metabolite (without pharmacological activity). Excretion: Excretion through the lungs, kidneys, feces, saliva and milk. Less than 7% is excreted through urine and feces in the original form, about 50% is excreted through the lungs as CO2, and about 30% is excreted through urine as N-oxide or N-demethylmetabolite, with a half-life of about 5 hours. No accumulation effect.
use	various insomnia, especially for patients who cannot tolerate the residual effect of the next morning. Pyrrolidone sedative hypnotics, hypnotic, sedative, anti-anxiety, muscle relaxation and anticonvulsant effects, the effect is faster. It can be used for the treatment of insomnia, especially for patients with temporary difficulty falling asleep and early awakening. Since the inhibitory effect on the respiratory system is extremely small, it does not affect the mental activity and alertness of the next morning. It can also be used for pre-anesthesia administration. used as sedative hypnotic medicine raw material/intermediate
adverse reactions	are related to dose and patient sensitivity. 1. Occasionally sleep, bitter mouth, dry mouth, muscle weakness, forgetting, drunkenness, some people have abnormal fear, aggressiveness, irritation or confusion, headache, fatigue. 2. Sudden withdrawal symptoms will occur after taking the drug for a long time (due to the short half-life of the drug, it will appear faster), and there may be mild agitation, anxiety, myalgia, tremor, rebound insomnia and nightmares, nausea and vomiting, rare Severe spasm, muscle tremor, and confusion (often secondary to mild symptoms).
drug interaction	1. when used with neuromuscular blockers or other central nervous system inhibitors, sedation will be enhanced. 2. With benzodiazepine anti-anxiety drugs or hypnotics, withdrawal symptoms can increase. 3. Intravenous injection of metoclopramide can increase the plasma concentration of this product. 4. When this product is taken with carbamazepine, the Cmax of this product increases, the Cmax of carbamazepine decreases, and the psychomotor damage increases. 5. Atropine and rifampicin increase the metabolism of this product, reduce the plasma concentration and hypnotic effect of this product. 6. Itraconazole and erythromycin can increase the AUC and half-life of this product, but the former does not change psychomotor activity, the latter is accompanied by psychomotor damage. 7. The combination of this product and ethanol can shorten the rapid eye movement (REM) period and increase psychomotor damage.
precautions	1. patients with myasthenia should pay attention to medical monitoring when taking drugs, and patients with respiratory insufficiency and liver and kidney insufficiency should adjust the dosage appropriately. 2. When using this product, it is absolutely forbidden to ingest alcoholic beverages. 3. Continuous medication should not be too long. Sudden withdrawal of medication can cause withdrawal syndrome. Caution should be taken. Mechanical operation and driving should not be used after taking medication. 4. In patients with liver cirrhosis, the plasma clearance capacity is significantly reduced due to the slowing of demethylation, and the dose should be adjusted. (2016-04-14)
contraindications	are forbidden for people who are allergic to this product, decompensated respiratory insufficiency, myasthenia gravis and severe sleep apnea syndrome.
Production method	Pyrazine-2, 3-dianhydride and 2-amino-5-chloropyridine are dissolved in acetonitrile and refluxed. Cooling, suction filtration, washing and drying. The obtained solid was suspended in water and acidified to Ph value 1 with lmol/L hydrochloric acid. After stirring, filter, wash with water and dry to obtain compound (I) with 92% yield. Compound (I) is refluxed with acetic anhydride. Cooling, suction filtration, washing and drying to obtain compound (II) with 82% yield. Compound (II) is dissolved in dioxane: water (19:1) solution, and potassium borohydride is slowly added under 13 ℃ and intense stirring. Pour into water, slowly add glacial acetic acid, filter, wash with water, dry, and then suspend in chloroform, stirring at room temperature. Suction filtration, washing and drying to obtain compound (Ⅲ) with 63% yield. Compound (III) is dissolved in anhydrous pyridine, and 4-methyl-1-piperazinoyl chloride hydrochloride is added at -10°C and stirred to react. Then the temperature is raised to 20 ℃, poured into ice water, let stand, filter, wash and dry, and the obtained crude product is refined to obtain white powdered zopiclone with 65% yield and melting point of 174~177 ℃. The last step can be carried out as follows: 2.4g of sodium hydride is dissolved in 60ml of anhydrous dimethylformamide, and 12g of 6-(5-chloro-2-pyridyl)-5-hydroxy -7-oxygen -5, 6-dihydropyrrolo [3,4-b] pyrazine is dissolved in 360ml of anhydrous dimethylformamide at -10 ℃. When the gas escape stopped, at -10 ℃, add 8.1 g1-chlorocarbonyl-4-methylpiperazine dissolved in 20ml of anhydrous dimethylformamide solution. Continue stirring for 3h, and let the temperature slowly rise to 20 ℃, then pour into 1540ml of ice water. The crystallized product was filtered and washed with 150ml of water and 100ml of isopropyl ether. The melting point of the dried product is 140 ℃. The crude product can be purified by the following methods: the crude product is dissolved in 600ml of ethyl acetate, and column chromatography is carried out with a column with a diameter of 4.2cm and 250g of silica gel. First use 3200ml ethyl acetate, then use 400ml ethyl acetate and methanol (19:1, volume ratio) mixed solution. Do not use the effluent for 2 times. Then use 800ml of ethyl acetate and methanol (9:1, volume ratio) mixture, 800ml of ethyl acetate and methanol (4:1, volume ratio) mixture to unfold. The two unfolded effluent are combined and concentrated to dryness under reduced pressure to obtain a product with a melting point of 170 ℃. The mixture of 190ml acetonitrile and isopropyl ether (1:1, volume ratio) was recrystallized to obtain zopiclone. Melting point 178 ℃.

Last Update：2024-04-09 20:49:11

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CAS: 43200-80-2
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43200-80-2

43200-80-2 Request for Quotation

Zopiclone

CAS: 43200-80-2

Molecular Formula: C17H17ClN6O3

43200-80-2 - Names and Identifiers

43200-80-2 - Physico-chemical Properties

43200-80-2 - Risk and Safety

43200-80-2 - Standard

Authoritative Data Verified Data

43200-80-2 - Trait

Authoritative Data Verified Data

melting point

absorption coefficient

43200-80-2 - Differential diagnosis

Authoritative Data Verified Data

43200-80-2 - Exam

Authoritative Data Verified Data

clarity and color of solution

optical rotation

chloride

Related substances

residual solvent

loss on drying

ignition residue

Heavy metals

43200-80-2 - Content determination

Authoritative Data Verified Data

43200-80-2 - Category

Authoritative Data Verified Data

43200-80-2 - Storage

Authoritative Data Verified Data

43200-80-2 - Zopiclone tablets

Authoritative Data Verified Data

trait

identification

examination

Content determination

category

specification

storage

43200-80-2 - Zopiclone capsules

Authoritative Data Verified Data

trait

identification

examination

Content determination

category

specification

storage

43200-80-2 - Reference Information

Supplier List

43200-80-2