41100-52-1

Basic information

• Product Name: Memantine HCl
• Synonyms: MEMANTINE HCL;LABOTEST-BB LT00233220;D-145;1,3-Dimethyl-5-aminoadamantane hydrochloride;1,3-DIMETHYLAMINOADAMANTANE HYDROCHLORIDE;1-AMINO-3,5-DIMETHYLADAMANTANE HCL;1-AMINO-3,5-DIMETHYLADAMANTANE HYDROCHLORIDE;1-AMINO-3,4-DIMETHYLADAMANTANE HYDROCHLORIDE
• CAS NO: 41100-52-1
• Molecular Formula: C₁₂H₂₁N*ClH
• Molecular Weight: 215.76
• EINECS: 255-219-6
• Product Categories: Adamantane derivatives;Antispasmodic;Antiparkinsonian;Adamantanes;Intermediates & Fine Chemicals;Pharmaceuticals;Glutamate receptor;Glutamate;Amines;API;Other APIs;raw materials
• Mol File: 41100-52-1.mol

Chemical Properties

• Melting Point: 292 °C
• Boiling Point: 239.8 °C at 760 mmHg
• Flash Point: 92.3 °C
• Appearance: White/Fine Powder
• Vapor Pressure: 0.0393mmHg at 25°C
• Storage Temp.: -20°C Freezer
• Solubility: Soluble in Water (up to 20 mg/ml)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in distilled water may be stored at -20°C for up to 2 months.
• Merck: 14,5806
• CAS DataBase Reference: Memantine HCl(CAS DataBase Reference)
• NIST Chemistry Reference: Memantine HCl(41100-52-1)
• EPA Substance Registry System: Memantine HCl(41100-52-1)

Safety Data

• Safety Statements: 24/25
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 41100-52-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Memantine HCl is used as a pharmaceutical secondary standard for application in quality control. It provides pharmaceutical laboratories and manufacturers with a convenient and cost-effective alternative to the preparation of in-house working standards.
Used in Alzheimer's Treatment:
Memantine HCl is used as an anti-Alzheimer's agent for reducing abnormal activity in the brain. It helps patients suffering from dementia by assisting them to think more clearly and perform their daily chores with ease.
Used in Antiparkinsonian Applications:
Memantine HCl is used as an antiparkinsonian and antispasmodic agent. It acts as a dopaminergic agonist, providing relief from the symptoms of Parkinson's disease.
Used in Neurodegenerative Disorder Research:
Memantine HCl is used as a test compound to determine the dynamic range and selectivity of retinal pigment epithelium tissue penetration. It is also used as a media supplement to serve as a control to study the neuroprotective effects of erythropoietin in N-methyl-D-aspartate receptor-induced toxicity. Additionally, it is used to intraperitoneally inject experimental animals to study its effect on traumatic injury.
Used in Drug Delivery Systems:
Memantine HCl is used in the development of novel drug delivery systems to enhance its applications and efficacy against cancer cells. Various organic and metallic nanoparticles have been employed as carriers for Memantine HCl delivery, aiming to improve its delivery, bioavailability, and therapeutic outcomes.
Brand Name:
The brand name for Memantine HCl is Namenda, which is marketed by Forest Laboratories in collaboration with Merz Pharmaceuticals. It was approved for the treatment of Alzheimer's disease in the US in October 2003 and is available in many European and Asian markets.

References

Reisberg, Barry, et al. New England Journal of Medicine 348.14 (2003): 1333-1341. Lipton, Stuart A. Nature reviews Drug discovery 5.2 (2006): 160-170.

References

1) Chen and Lipton (1997), Mechanism of memantine block of NMDA-activated channels in rat retinal ganglion cells: uncompetitive antagonism; J. Physiol. 499 27 2) Chen et al. (1998), Neuroprotective concentrations of the N-methyl-D-aspartate open-channel blocker memantine are effective without cytoplasmic vacuolation following post-ischemic administration and do not block maze learning or long-term potentiation; Neuroscience 86 1121 3) Lipton et al. (2005), The molecular basis of memantine action in Alzheimer’s disease and other neurologic disorders: low-affinity, uncompetitive antagonism; Curr. Alzheimer. Res. 2 155 4) Parsons et al. (1999), Memantine is a clinically well tolerated N-methyl-D-aspartate (NMDA) receptor antagonist—a review of preclinical data; Neuropharmacology 38 735 5) Witt et al. (2004), Memantine hydrochloride; Nat. Rev. Drug Discov. 3 109

Biochem/physiol Actions

Memantine is effective against Alzheimer′s disease and Parkinson′s disease. It is also useful in treating epilepsy, motor neurone disease and trauma.

Synthesis

Memantine (XV) or 1-amino- 3,5-dimethyladamantane hydrochloride was first synthesized by Lilly as an anti-diabetic agent but was ineffective in lowering blood sugar. Several syntheses have been detailed in the literature. However the simplest synthesis of the drug was done in one step from the commercially available 3,5-dimethyl adamantine (122). Treatment of 122 with nitrogen trichloride (CAUTION: very explosive gas!) in the presence of aluminum trichloride (ratio of 1.5:1.2) gave the desired amino adamantine in 86% yield. However, a much safer alternative has been reported by Lilly scientists. Heating the commercially available 3,5-dimethyladamantane 122 in bromine gave the bromo derivative 123 (86%) which was then reacted with sulfuric acid in acetonitrile to provide quantitatively acetyl amino derivative 124 after aqueous workup. Hydrolysis of the acetyl group was done by heating 124 with sodium hydroxide in diethylene glycol to give 1-amino -3,5- adamantane (96%), which was then made into the hydrochloride salt in ether and recrystallized from ether and alcohol mixture to provide the final product memantine hydrochoride XV.

InChI:InChI=1/C12H21N.ClH/c1-10-3-9-4-11(2,6-10)8-12(13,5-9)7-10;/h9H,3-8,13H2,1-2H3;1H

Synthetic route

2,2,2-trichloroethyl 3,5-dimethyladamantylcarbamate (1058345-42-8) → memantine hydrochloride (41100-52-1)

Conditions	Yield
Stage #1: 2,2,2-trichloroethyl 3,5-dimethyladamantylcarbamate With acetic acid; zinc at 20℃; for 2h; Stage #2: With acetyl chloride In methanol at 40℃; for 16h; Heating;	100%

1-acetamido-3,5-dimethyladamantane (19982-07-1) → memantine hydrochloride (41100-52-1)

Conditions	Yield
Stage #1: 1-acetamido-3,5-dimethyladamantane With sodium hydroxide In diethylene glycol for 6h; Reflux; Stage #2: With water In dichloromethane; diethylene glycol at 20℃; for 0.25h; Stage #3: With hydrogenchloride In ethyl acetate at 0 - 30℃; for 6h;	99.3%
Stage #1: 1-acetamido-3,5-dimethyladamantane With potassium hydroxide; butan-1-ol at 20 - 132℃; for 10.33 - 10.5h; Stage #2: With hydrogenchloride In water at 20 - 25℃; for 0.666667h;	95%
Stage #1: 1-acetamido-3,5-dimethyladamantane With sodium hydroxide In ethylene glycol at 150 - 160℃; for 0.5h; Large scale; Stage #2: With hydrogenchloride In ethyl acetate Large scale;	82.78%

3,5-dimethyl-1-bromoadamantane (941-37-7) + urea (57-13-6) → memantine hydrochloride (41100-52-1)

Conditions	Yield
Stage #1: 3,5-dimethyl-1-bromoadamantane; urea In 1-methyl-pyrrolidin-2-one at 120℃; for 4h; Stage #2: With sodium hydroxide In 1-methyl-pyrrolidin-2-one at 120℃; for 6h; Stage #3: With hydrogenchloride In 1-methyl-pyrrolidin-2-one; water at 25℃; for 16h; Solvent; Temperature;	97%

1-formamido-3,5-dimethyltricyclo[3.3.1.13,7]decane (351329-88-9) → memantine hydrochloride (41100-52-1)

Conditions	Yield
With hydrogenchloride In water at 100℃; for 5h;	94%
Stage #1: 1-formamido-3,5-dimethyltricyclo[3.3.1.13,7]decane With water; sodium hydroxide In methanol for 12h; Reflux; Stage #2: With hydrogenchloride In methanol; n-heptane at 60 - 65℃; Product distribution / selectivity;	86%
With hydrogenchloride In hexane; water for 2.5h; Reflux;	84.65%

N-((1,3,5,7)-3,5-dimethyladamantan-1-yl)-1,1,1-trifluoromethanesulfonamide (1309688-17-2) → memantine hydrochloride (41100-52-1)

Conditions	Yield
Stage #1: N-((1,3,5,7)-3,5-dimethyladamantan-1-yl)-1,1,1-trifluoromethanesulfonamide With potassium carbonate; 1-bromomethyl-4-nitro-benzene In acetone at 20℃; Stage #2: With caesium carbonate In tetrahydrofuran at 50℃; for 14h; Stage #3: With hydrogenchloride In tetrahydrofuran; water	92%

memantine* (19982-08-2) → memantine hydrochloride (41100-52-1)

Conditions	Yield
With hydrogenchloride In water; acetone at -5 - 30℃; for 5h;	91.9%
With hydrogenchloride pH=6; Gas phase;	88%
With hydrogenchloride In water; acetone at 0 - 10℃; Solvent;	88%

1-nitro-3,5-dimethyl-adamantane (6588-68-7) → memantine hydrochloride (41100-52-1)

Conditions	Yield
Stage #1: 1-nitro-3,5-dimethyl-adamantane With iron; acetic acid at 20℃; for 4.5h; Stage #2: With hydrogenchloride In ethyl acetate for 0.5h;	449.2 g

1-acetamido-3,5-dimethyladamantane p-toluenesulfonate → memantine hydrochloride (41100-52-1)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: ammonia / dichloromethane; water / 0.5 h / 25 - 30 °C / pH 9.5 - 10.0 2.1: sodium hydroxide / diethylene glycol / 10 h / Heating / reflux 2.2: 2 h / 10 - 15 °C View Scheme

3, 5-dimethyl-1-adamantyl methyl ketone (40430-57-7) → memantine hydrochloride (41100-52-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: methanol; O-benzenesulfonyl-acetohydroxamic acid ethyl ester; toluene-4-sulfonic acid / 12 h / Inert atmosphere; Reflux 2: hydrogenchloride / acetone / 3 h / 23 °C / Inert atmosphere View Scheme

7-bromoheptyl alcohol (10160-24-4) + memantine hydrochloride (41100-52-1) → 7-((3,5-dimethyladamantan-1-yl)amino)heptan-1-ol (1402933-70-3)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 48h;	92%

5-Chlorovaleroyl chloride (1575-61-7) + memantine hydrochloride (41100-52-1) → 5-chloro-N-(3,5-dimethyladamantan-1-yl)pentanamide (1402933-98-5)

Conditions	Yield
With potassium carbonate In acetonitrile at 20℃; for 4h;	91%

(R)-2-((1S,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl) propanoic acid + memantine hydrochloride (41100-52-1) → (cis)-(2R)-N-(3,5-dimethyladamantan-1-yl)-2-(4-(6-fluoroquinolin-4-yl)cyclohexyl)propanamide

Conditions	Yield
With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 1h;	91%

acetyl chloride (75-36-5) + memantine hydrochloride (41100-52-1) → 1-acetamido-3,5-dimethyladamantane (19982-07-1)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 3h; Solvent;	91%

9-bromononan-1-ol (55362-80-6) + memantine hydrochloride (41100-52-1) → 9-((3,5-dimethyladamantan-1-yl)amino)nonan-1-ol (1402933-72-5)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 48h;	90%

formic acid (64-18-6) + memantine hydrochloride (41100-52-1) → 1-formamido-3,5-dimethyltricyclo[3.3.1.13,7]decane (351329-88-9)

Conditions	Yield
With titanium sulfate at 80℃; for 5h; Reagent/catalyst; Temperature;	90%

N,N-dimethyl-formamide (68-12-2, 33513-42-7) + memantine hydrochloride (41100-52-1) → 1-formamido-3,5-dimethyltricyclo[3.3.1.13,7]decane (351329-88-9)

Conditions	Yield
With titanium(IV) oxide at 105℃; for 3h; Reagent/catalyst;	90%

acetic anhydride (108-24-7) + memantine hydrochloride (41100-52-1) → 1-acetamido-3,5-dimethyladamantane (19982-07-1)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 2.5h; Solvent;	90%

1-bromo-6-hexanol (4286-55-9) + memantine hydrochloride (41100-52-1) → 6-((3,5-dimethyladamantan-1-yl)amino)hexan-1-ol (1402933-69-0)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 48h;	89%

ethyl 2-isothiocyanatoacetate (24066-82-8) + memantine hydrochloride (41100-52-1) → ethyl {[(3,5-dimethyladamantan-1-yl)carbamothioyl]amino}acetate

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 80℃; for 12h;	89%

5-tosyloxy-3-oxapentanol (118591-58-5) + memantine hydrochloride (41100-52-1) → 2-(2-((3,5-dimethyladamantan-1-yl)amino)ethoxy)ethanol (1402934-02-4)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 48h;	88%

2-((2-hydroxyethyl)thio)ethyl 4-methylbenzenesulfonate (1402934-00-2) + memantine hydrochloride (41100-52-1) → 2-((2-((3,5-dimethyladamantan-1-yl)amino)ethyl)thio)ethanol

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 48h;	87%

memantine hydrochloride (41100-52-1) + Glycine ethyl ester isocyanate (2949-22-6) → ethyl {[(3,5-dimethyladamantan-1-yl)carbamoyl]amino}acetate

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 20℃; for 12h;	87%

memantine hydrochloride (41100-52-1) + toluene-4-sulfonic acid 4-tert-butoxycarbonylaminobutyl ester (180851-50-7) → tert-butyl (4-((3,5-dimethyladamantan-1-yl)amino)butyl)carbamate

Conditions	Yield
With potassium carbonate; potassium iodide In N,N-dimethyl-formamide under 12929 Torr; for 1h; Microwave irradiation;	87%

8-bromooctanol (50816-19-8) + memantine hydrochloride (41100-52-1) → 8-((3,5-dimethyladamantan-1-yl)amino)octan-1-ol (1402933-71-4)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 48h;	86%

memantine hydrochloride (41100-52-1) + 4-Chlorobutanoyl chloride (4635-59-0) → 4-chloro-N-(3,5-dimethyladamantan-1-yl)butanamide (1402933-97-4)

Conditions	Yield
With potassium carbonate In acetonitrile at 20℃; for 4h;	86%

formamide (77287-34-4, 77287-35-5, 60100-09-6) + memantine hydrochloride (41100-52-1) → 1-formamido-3,5-dimethyltricyclo[3.3.1.13,7]decane (351329-88-9)

Conditions	Yield
With copper(II) choride dihydrate at 40℃; for 4h;	86%

6-chlorohexanoyl chloride (19347-73-0) + memantine hydrochloride (41100-52-1) → 6-chloro-N-(3,5-dimethyladamantan-1-yl)hexanamide (1402933-99-6)

Conditions	Yield
With potassium carbonate In acetonitrile at 20℃; for 4h;	85%

9-bromononanoic acid (41059-02-3) + memantine hydrochloride (41100-52-1) → 9-bromo-N-(3,5-dimethyladamantyl)nonamide

Conditions	Yield
With 2-chloro-1,3-dimethyl-4,5-dihydro-1H-imidazolium chloride; triethylamine In dichloromethane at 0 - 20℃; for 18h;	85%

4-cyanobenzoic Acid (619-65-8) + memantine hydrochloride (41100-52-1) → C20H24N2O

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; Inert atmosphere; Cooling with ice;	81%

3-(prop-2-en-1-yldisulfanyl)propanoic acid (805983-04-4) + memantine hydrochloride (41100-52-1) → 3-(prop-2-en-1-yldisulfanyl)-N-((1r,3R,5S,7r)-3,5-dimethyladamantan-1-yl)propanamide (1215295-30-9)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; Inert atmosphere; Cooling with ice;	79%

memantine hydrochloride (41100-52-1) + 6-((tert-butoxycarbonyl)amino)hexyl 4-methylbenzenesulfonate (86536-92-7) → tert-butyl (6-((3,5-dimethyladamantan-1-yl)amino)hexyl)carbamate

Conditions	Yield
With potassium carbonate; potassium iodide In N,N-dimethyl-formamide under 12929 Torr; for 1h; Microwave irradiation;	79%

Upstream product

• 19982-08-2 memantine* 
• 19982-07-1 1-acetamido-3,5-dimethyladamantane 
• 707-36-8 1-chloro-3,5-dimethyl-adamantane 
• 351329-88-9 1-formamido-3,5-dimethyltricyclo[3.3.1.1^3,7]decane 
• 1058345-42-8 2,2,2-trichloroethyl 3,5-dimethyladamantylcarbamate 
• 702-79-4 1,3-dimethyladamantane 
• 75-05-8 acetonitrile 
• 941-37-7 3,5-dimethyl-1-bromoadamantane 
• 707-37-9 1,3-dimethyl-5-adamantanol 
• 6588-68-7 1-nitro-3,5-dimethyl-adamantane 
• 57-13-6 urea 
• 40430-57-7 3, 5-dimethyl-1-adamantyl methyl ketone 
• 1309688-17-2 N-((1,3,5,7)-3,5-dimethyladamantan-1-yl)-1,1,1-trifluoromethanesulfonamide 
• 947238-46-2 2-chloro-N-(3,5-dimethyl-adamantan-1-yl)-acetamide 

Downstream Products

• 19982-08-2 memantine* 
• 1402933-83-8 3-((tert-butoxycarbonyl)(3,5-dimethyladamantan-1-yl)amino)propyl 4-methylbenzenesulfonate 
• 1402933-84-9 4-((tert-butoxycarbonyl)(3,5-dimethyladamantan-1-yl)amino)butyl 4-methylbenzenesulfonate 
• 1402933-85-0 5-((tert-butoxycarbonyl)(3,5-dimethyladamantan-1-yl)amino)pentyl 4-methylbenzenesulfonate 
• 1402933-72-5 9-((3,5-dimethyladamantan-1-yl)amino)nonan-1-ol 
• 1420044-11-6 C₂₃H₃₆N₂ 
• 1204184-74-6 2-(3,5-dimethyladamantan-1-yl)isoindoline-1,3-dione 
• 136860-49-6 1-isothiocyanato-3,5-dimethyladamantane 
• 351329-88-9 1-formamido-3,5-dimethyltricyclo[3.3.1.1^3,7]decane 
• 19982-07-1 1-acetamido-3,5-dimethyladamantane 
• 1340545-88-1 memantine glycine 
• 63971-25-5 3-amino-5,7-dimethyladamantan-1-ol 

Relevant articles and documents

Preparation method of 3,5-dimethyladamantanamine hydrochloride

The invention discloses a preparation method of 3,5-dimethyl adamantanamine hydrochloride. The method comprises the following steps: adding 1-nitro-3,5-dimethyladamantane into a first solvent, and carrying out hydrogenation reaction in the presence of a catalyst; desolventizing the hydride material, adding water, and distilling with water vapor; extracting the distillate with a second solvent, adding hydrochloric acid, performing azeotropic dehydration, and performing crystallization separation to prepare the 3,5-dimethyladamantanamine hydrochloride. The method has the advantages of cheap and easily available raw materials, mild reaction conditions, high yield, good product quality and easy realization of industrial production.

Green and efficient preparation method of medicament for treating Alzheimer's disease

The invention discloses a green and efficient preparation method of a medicament for treating Alzheimer's disease, which comprises the following steps of reacting 1-bromo-3, 5-dimethyl adamantane serving as a raw material under the action of acetonitrile, pyridine p-toluenesulfonate and acid to synthesize 1-acetamido-3, 5-dimethyl adamantane, then carrying out reflux reaction hydrolysis in organicweak acid to obtain 1-amino-3, 5-dimethyl adamantane, and finally acidifying into salt by using hydrochloric acid to obtain a product with the purity of more than 99%. On one hand, by adding pyridinep-toluenesulfonate, the operation risk caused by using a large amount of concentrated sulfuric acid is avoided, the reaction time is shortened, and the reaction temperature is reduced; on the other hand, 1-acetamido-3, 5-dimethyl adamantane is refined and concentrated in alcohol water and then subjected to amide hydrolysis in organic weak acid, the reaction proceeding degree is improved, the reaction temperature and the high requirement of high-temperature strong-alkali reaction for equipment are reduced, the organic weak acid can be recycled and reused, the method is more environmentally friendly, the production cost is reduced, - the reaction yield is high and the product purity is good.

PROCESS FOR PREPARATION OF MEMANTINE

The present invention provides an improved process of manufacturing 1-Bromo-3,5-dimethyladamantane compound of formula-IV starting from 1,3-dimethyladamantane that avoids use of liquid bromine and minimizes the use of hazardous chemicals. The present invention also provides use of 1-Bromo-3,5-dimethyladamantane prepared by the process of present invention in the process of producing Memantine hydrochloride and pharmaceutical compositions thereof.

Preparation method of memantine hydrochloride (by machine translation)

The preparation method of the memantine hydrochloride, comprises the following steps,1 - bromo - 333355-dimethyladamantane, used as a hydrolysis reagent, to hydrolyze the formamide group to obtain a finished product of memantine hydrochloride . The method disclosed by the invention is relatively mild in preparation conditions and low in cost, obtained by hydrolysis of the amino substituent, by using formamide as a hydrolysis reagent . The method, further comprises the following steps: preparing a finished product of, memantine hydrochloride by using, a sodium hydroxide solution as a, hydrolysis reagent. (by machine translation)

Preparation method of medicine for treating neurological function diseases

The invention discloses a preparation method of a medicine for treating neurological function diseases, which comprises the following steps: 1) adding 1-bromo-3,5-dimethyl adamantane, acetonitrile, acatalyst 1 and a catalyst 2 into a reaction kettle, stirring to react, adding a certain amount of water into the reaction solution, cooling to precipitate a solid, adding the solid into a certain proportion of an alcohol water solution, and carrying out hot melting and cold precipitation to obtain 1-acetamido-1,3-dimethyl adamantane; and (2) carrying out high-temperature reaction on 1-acetamido-1,3-dimethyl adamantane and sodium hydroxide in ethylene glycol, adding a certain amount of purified water, extracting by adopting dichloromethane, concentrating under reduced pressure, adding an ethylacetate hydrochloride solution into the concentrated solution, cooling to allow crystal growing, carrying out suction filtration, and drying to obtain memantine hydrochloride. According to the method,the catalyst 1 and the catalyst 2 are used as reaction catalysts, so that the operation risk caused by the use of concentrated sulfuric acid is avoided, the reaction time is shortened, and the side reaction is reduced. The post-treatment is simple, the reaction yield is high, and the product purity is good.

Memantine hydrochloride impurity compound and preparation method thereof

The invention discloses a preparation method of a memantine hydrochloride impurity compound 1-nitro-7-hydroxy-3,5-dimethyl adamantane. According to the preparation method, 1-bromo-3,5-dimethyl adamantane is taken as a raw material and carries out a substitution reaction with acetamide in a molten state, then hydrolysis and salt forming happen in an alkaline environment, and finally the target product is prepared after hydroxylation and oxidation. The impurity compound is used as a reference substance for memantine hydrochloride quality control.

Memantine hydrochloride synthesis method

The invention provides a memantine hydrochloride synthesis method, and belongs to the technical field of medicine synthesis. The preparation method comprises the following steps: carrying out a substitution reaction on 1-bromo-3,5-dimethyladamantane and acetamide to obtain 1-acetamido-3,5-dimethyladamantane, mixing the 1-acetamido-3,5-dimethyladamantane, an alcohol and an alkali, carrying out an alcoholysis reaction to obtain 1-amino-3,5-dimethyladamantane, and finally carrying out an acidification reaction on the 1-amino-3,5-dimethyladamantane and hydrochloric acid to obtain memantine hydrochloride. According to the method of the invention, 1-bromo-3,5-dimethyl adamantane and acetamide are used as the starting raw materials, so the sources of the raw materials are wide, the use of acetonitrile is avoided, and no pollution is caused to the human body and the environment; the use of catalysts is avoided in the whole reaction process, the reaction product is easy to separate, and the yield of the obtained memantine hydrochloride is high; and the method is mild in reaction condition and suitable for industrial production.

Cerium-Catalyzed C-H Functionalizations of Alkanes Utilizing Alcohols as Hydrogen Atom Transfer Agents

Modern photoredox catalysis has traditionally relied upon metal-to-ligand charge-transfer (MLCT) excitation of metal polypyridyl complexes for the utilization of light energy for the activation of organic substrates. Here, we demonstrate the catalytic application of ligand-to-metal charge-transfer (LMCT) excitation of cerium alkoxide complexes for the facile activation of alkanes utilizing abundant and inexpensive cerium trichloride as the catalyst. As demonstrated by cerium-catalyzed C-H amination and the alkylation of hydrocarbons, this reaction manifold has enabled the facile use of abundant alcohols as practical and selective hydrogen atom transfer (HAT) agents via the direct access of energetically challenging alkoxy radicals. Furthermore, the LMCT excitation event has been investigated through a series of spectroscopic experiments, revealing a rapid bond homolysis process and an effective production of alkoxy radicals, collectively ruling out the LMCT/homolysis event as the rate-determining step of this C-H functionalization.

Method for preparing memantine hydrochloride

The invention belongs to the field of pharmaceutical synthesis and particularly relates to a method for preparing memantine hydrochloride. The method includes that 1-minus chlorine-3,5-dimethyl is taken as a raw material which is amidated via methanamide and hydrolyzed via hydrochloric acid to obtain a target product directly with a one-step method, wherein the yielding rate can be up to 80%, andthe product purity excesses 99.0%. Compared with a traditional synthesis process, the novel process is simple in synthesis steps, product cost is greatly reduced, little pollution is caused to the environment, and environmental problems caused by the production of the memantine hydrochloride are greatly alleviated.