768-94-5

Basic information

• Product Name: Amantadine
• Synonyms: 1-ADAMANTYLAMINE;1-ADAMANTANAMINE;1-ADAMANTAMINE;1-AMINOADAMANTANE;ADAMANTANAMINE;AMANTADINE;tricyclo[3.3.1.1(3,7)]decane-1-amine;1-Adamantanamin
• CAS NO: 768-94-5
• Molecular Formula: C10H17N
• Molecular Weight: 151.25
• EINECS: 212-201-2
• Product Categories: Adamantane derivatives;A-AM;Amines;Bioactive Small Molecules;Building Blocks;C10;Cell Biology;Chemical Synthesis;Nitrogen Compounds;Organic Building Blocks;neurochemistry
• Mol File: 768-94-5.mol

Chemical Properties

• Melting Point: 206-208 °C(lit.)
• Boiling Point: 263.29°C (rough estimate)
• Flash Point: 95.974 °C
• Appearance: White to cream/Powder
• Density: 0.9510 (rough estimate)
• Vapor Pressure: 0.0852mmHg at 25°C
• Refractive Index: 1.5220 (estimate)
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• Solubility: 1 M HCl: soluble5%, clear to hazy, colorless to faint yellow or
• PKA: 10.1(at 25℃)
• Water Solubility: Soluble in organic solvents. Insoluble in water.
• Merck: 14,374
• BRN: 2204333
• CAS DataBase Reference: Amantadine(CAS DataBase Reference)
• NIST Chemistry Reference: Amantadine(768-94-5)
• EPA Substance Registry System: Amantadine(768-94-5)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 22-36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• RTECS: YD1925000
• F: 10-34
• Hazardous Substances Data: 768-94-5(Hazardous Substances Data)

Usage

Inhibitor

The anti-influenza A compound amantadine acts by blocking the M2 ion channel which is required for uptake of protons into the interior of the virus to permit acid-promoted viral uncoating (decapsidation).

Chemical Properties

White to cream powder

Uses

Different sources of media describe the Uses of 768-94-5 differently. You can refer to the following data:
1. Building block for an L-piperidinamide catalyst used in an enantioselective Strecker reaction of phosphinoyl imines.1
2. Amantadine is a primary amine derivative of adamantane. It has an effect on mycoviruses, which are RNA-containing viruses. It has a very narrow spectrum of action and is used only for treating and preventing influenza A. It is also used for treating Parkinsonism. The exact mechanism of antiviral action of amantadine is not completely understood. It is believed that it is an ion channel blocker. It has also been suggested that amantadine inhibits absorption of viral particles into the host cell, which is expressed in the breakdown of diffusion of the virus into the cell, or inhibition of the “stripping process” of the virus. The main use is for the prevention of type A2 influenza. Synonyms of this drug are simmetrel, viregit, mantadan, and others.
3. Amantadine is an antiviral drug. The properties in amantadine, which relieve symptoms of Parkinsonism were discovered by accident. Treatment of Parkinsonism with a combination of levodopa, anticholinergic drugs, and amantadine gives better results than using any of these drugs individually.

Definition

ChEBI: A member of the class of adamantanes that is used as an antiviral and antiparkinson drug.

Biological Functions

Amantadine was originally introduced as an antiviral compound, but it is modestly effective in treating symptoms of parkinsonism. It is useful in the early stages of parkinsonism or as an adjunct to levodopa therapy. Its mechanism of action in parkinsonism is not clear, but amantadine may affect dopamine release and reuptake. Additional sites of action may include antagonism at muscarinic and N-methyl-Daspartate (NMDA) receptors. Adverse effects include nausea, dizziness, insomnia, confusion, hallucinations, ankle edema, and livedo reticularis. Amantadine and the anticholinergics may exert additive effects on mental functioning

Synthesis Reference(s)

Journal of the American Chemical Society, 91, p. 6457, 1969 DOI: 10.1021/ja01051a047Synthesis, p. 457, 1976

Antimicrobial activity

It inhibits influenza A virus replication at concentrations of 0.2– 0.6 mg/L, but has little or no activity against influenza B or C.

Acquired resistance

Resistance is the consequence of mutations in amino acid positions 27, 30 and 31 in the M2 transmembrane sequence. Cross-resistance between amantadine and rimantadine is universal. Influenza H3N2 strains worldwide are now resistant, but seasonal H1N1 strains remain susceptible. Postexposure family prophylaxis results in the prompt emergence of drug resistance after onset of treatment.

General Description

Amantadine has been used for years as a treatment for Parkinson disease. The adamantanamines have twomechanisms in common:they inhibit an early step in viralreplication, most likely viral uncoating,and in somestrains, they affect a later step that probably involves viral assembly,possibly by interfering with hemagglutinin processing.The main biochemical locus of action is the influenzatype A virus M2 protein, which is an integral membrane proteinthat functions as an ion channel. The M2 channel is a protontransport system. By interfering with the function of theM2 protein, the adamantanamines inhibit acid-mediated dissociationof the ribonucleoprotein complex early in replication.They also interfere with transmembrane proton pumping,maintaining a high intracellular proton concentrationrelative to the extracellular concentration and enhancingacidic pH-induced conformational changes in the hemagglutininduring its intracellular transport at a later stage. The conformationalchanges in hemagglutinin prevent transfer of thenascent virus particles to the cell membrane for exocytosis.

Flammability and Explosibility

Flammable

Pharmaceutical Applications

A symmetrical synthetic C-10 tricyclic amine with an unusual cage-like structure, supplied as the hydrochloride for oral administration.

Mechanism of action

Amantadine hydrochloride (1-adamantanamine hydrochloride) is a symmetric, tricyclic, primary amine that inhibits penetration of RNA viral particles into the host cell. It also inhibits the early stages of viral replication by blocking the uncoating of the viral genome and the transfer of nucleic acid into the host cell.

Pharmacokinetics

Oral absorption: >90% Cmax 200 mg oral per day: 0.4–0.9 mg/L after c. 4–6 h Plasma half-life: 9.7–14.5 h Volume of distribution: 10.4 L/kg Plasma protein binding: 65% Absorption and distribution Absorption after oral administration is almost complete. Levels in secretions approach plasma concentrations. Metabolism and excretion About 56% of a single oral dose is excreted unchanged within 24 h by the kidney. Altogether 90% of an oral dose is excreted in the urine with a mean elimination half-life of 11.8 h in subjects with normal renal function. In elderly men, the half-life is 28.9 h and in patients with renal insufficiency half-lives of 18.5 h to 33.8 days have been observed. The renal clearance is around 398 mL/min (range 112–772 mL/min), indicating active secretion as well as glomerular filtration. Less than 5% of a dose is removed during hemodialysis and average half-lives of 8.3 and 13 days have been reported in patients on chronic hemodialysis. Extreme care must be taken to ensure that drug does not accumulate to toxic levels.

Clinical Use

Different sources of media describe the Clinical Use of 768-94-5 differently. You can refer to the following data:
1. Prevention and treatment of influenza A H1N1 infections
2. Amantadine is used for the treatment of diseases caused by influenza A strains.

Side effects

Embryotoxicity and teratogenicity have been observed in rats receiving 50 mg/kg per day, about 15 times the usual human dose. Neurological side effects include drowsiness, insomnia, light-headedness, difficulty in concentration, nervousness, dizziness and headache in up to 20% of individuals. Other side effects include anorexia, nausea, vomiting, dry mouth, constipation and urinary retention. All develop during the first 3–4 days of therapy and are reversible by discontinuing the drug. An exception to rapid onset of adverse reactions is livedo reticularis. Convulsions, hallucinations and confusion are dose related, usually occurring at levels in excess of 1.5 mg/L; convulsions may occur at a lower threshold in patients with a history of epilepsy and the drug is best avoided in such patients.

Safety Profile

Poison by intraperitoneal route.Moderately toxic by ingestion. Mutation data reported.When heated to decomposition it emits toxic fumes ofNOx. Used as an antiviral agent.

Synthesis

Amantadine, 1-adamantanamine (10.1.12), is synthesized from adamantane. It is directly brominated to 1-bromadamantane (10.1.10), which in Ritter reaction conditions when heated with a mixture of acetonitrile and concentrated sulfuric acid transforms into 1-acetylaminoadamantane (10.1.11). Hydrolysis of this product using alkali leads to the formation of amantadine (10.1.12) [16,17].

Purification Methods

Dissolve the amine in Et2O, dry it over KOH, evaporate and sublime it in vacuo. [Stetter et al. Chem Ber 93 226 1960.]

InChI:InChI=1/C10H17N/c11-10-4-7-1-8(5-10)3-9(2-7)6-10/h7-9H,1-6,11H2/t7-,8-,9-,10-

Synthetic route

1-nitroadamantane (7575-82-8) → 1-Adamantanamine (768-94-5)

Conditions	Yield
With sodium dithionite; potassium carbonate; 1,1′-dioctyl-4,4′-bipyridinium In water; acetonitrile at 35℃; for 24h;	98%
With hydrazine hydrate; ammonia In ethanol Reagent/catalyst; Solvent;

(3r,5r,7r)-N-hydroxyadamantane-1-carboxamide (28309-44-6) → 1-Adamantanamine (768-94-5)

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide at 90℃; for 3h; Lossen Rearrangement;	98%
Stage #1: adamantane-1-carboxylic acid hydroxyamide With acetic anhydride; potassium carbonate In dimethyl sulfoxide at 50℃; for 6h; Lossen Rearrangement; Stage #2: With hydrogenchloride In water; dimethyl sulfoxide at 0℃;	67%
Stage #1: adamantane-1-carboxylic acid hydroxyamide With potassium carbonate In dimethyl sulfoxide at 90℃; for 3h; Lossen Rearrangement; Stage #2: With hydrogenchloride In water; dimethyl sulfoxide at 20℃; for 1h;

Adamantan-1-yl-[2,2,2-trifluoro-1-phenyl-eth-(Z)-ylidene]-amine (141903-89-1) → 1,1,1-trifluoroacetophenone (434-45-7) + 1-Adamantanamine (768-94-5)

Conditions	Yield
With water; boric acid In ethanol at 80℃; for 8h;	A n/a B 96%

Adamantan-1-yl-[2,2,2-trifluoro-1-phenyl-eth-(Z)-ylidene]-amine (141903-89-1) → 1-Adamantanamine (768-94-5)

Conditions	Yield
With boric acid In ethanol Heating;	96%

1-Adamantyl bromide (768-90-1) → 1-Adamantanamine (768-94-5)

Conditions	Yield
With ammonium bicarbonate at 135℃; for 6h; Concentration; Temperature; Autoclave;	94.7%
Stage #1: 1-Adamantyl bromide With magnesium Inert atmosphere; Stage #2: With 3,3’-di-tert-butyl oxaziridine In diethyl ether at 20℃; for 6h; Inert atmosphere;	55%
With urea
With urea at 170 - 190℃;

amantadine hydrochloride (665-66-7) → 1-Adamantanamine (768-94-5)

Conditions	Yield
With sodium chloride; sodium hydroxide In water	94%
With sodium hydroxide In water
With sodium hydroxide In dichloromethane; water

N-(1-adamantyl)acetamide (880-52-4) → 1-Adamantanamine (768-94-5)

Conditions	Yield
With ammonium bromide; ethylenediamine at 100℃; for 5h; Microwave irradiation;	93%
With ammonium bromide; ethylenediamine at 90℃; for 10h; Microwave irradiation; Inert atmosphere; neat (no solvent);	92%
With sodium hydroxide In 1,2-dimethoxyethane at 135℃; for 12h; Solvent; Temperature; Time;	90%

1-Azidoadamantane (24886-73-5) → 1-Adamantanamine (768-94-5)

Conditions	Yield
With 1,3-diadamantane-4,5-dihydroimidazole chloride; potassium tert-butylate; bis(pinacol)diborane; copper(l) chloride In toluene at 25℃; for 4h; Schlenk technique; Inert atmosphere;	92%
With PEG3400-PPh3 conjugate In dichloromethane for 4.5h; Ambient temperature;	91%
With hydrazine hydrate; palladium dihydroxide; pyrographite In methanol for 2h; Heating;	88%

1-tosylaminoadamantane (56432-99-6) → 1-Adamantanamine (768-94-5)

Conditions	Yield
With propylamine; lithium In ethylenediamine at 20 - 42℃; for 2h; Reduction;	91%

2,2,2-trichloroethyl ((3s,5s,7s)-adamantan-1-yl)carbamate (17341-91-2) → 1-Adamantanamine (768-94-5)

Conditions	Yield
With indium; ammonium chloride In ethanol for 6h; Heating;	91%

ethylbenzene (100-41-4) + [Cl2NN]Cu-NHAd (1215209-26-9) → N-(1-phenylethyl)-1-aminoadamantane (1034159-49-3) + 1-Adamantanamine (768-94-5)

Conditions	Yield
In n-heptane at 20℃; for 24h; Inert atmosphere;	A 87% B n/a

2-((3r,5r,7r)-adamantan-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1357000-33-9) → 1-Adamantanamine (768-94-5)

Conditions	Yield
With O-Methylhydroxylamin; potassium tert-butylate In tetrahydrofuran; toluene at 80℃; for 16h; Inert atmosphere; Sealed tube;	85%

(5-mesityl-1,9-(2,4,6-Ph3C6H2)dipyrrin)Fe(NAd) → 1-Adamantanamine (768-94-5) + 2-[N-(1-adamantyl)]aminomethylbenzene (3717-60-0)

Conditions	Yield
With 2,4,6-tri-tert-butylphenoxol In (2)H8-toluene at 80℃; for 24h; Schlenk technique; Inert atmosphere;	A 84% B 14%

INDANE (496-11-7) + [Cl2NN]Cu-NHAd (1215209-26-9) → N-(2,3-dihydro-1H-inden-1-yl)-1-aminoadamantane (1034159-52-8) + 1-Adamantanamine (768-94-5)

Conditions	Yield
In n-heptane at 20℃; for 24h; Inert atmosphere;	A 81% B n/a

octafluoronaphthalene (313-72-4) + N-(adamant-1-yl)-N'-trimethylsilyl sulfur diimide (476007-25-7) → 1-Adamantanamine (768-94-5) + 4,5,6,7,8,9-hexafluoronaphtho[1,2-c][1,2,5]thiadiazole

Conditions	Yield
With cesium fluoride In acetonitrile for 1.5h;	A n/a B 80%

[Cl2NN]Cu-NHAd (1215209-26-9) + toluene (108-88-3) → 1-Adamantanamine (768-94-5) + 2-[N-(1-adamantyl)]aminomethylbenzene (3717-60-0) + N-(-adamantan-1-yl)-1-phenylmethanimine (57527-54-5, 3717-59-7)

Conditions	Yield
In n-heptane at 60℃; for 24h; Inert atmosphere;	A n/a B 70% C 15%

1-adamantyl-diallylamine (3667-65-0) → 1-Adamantanamine (768-94-5)

Conditions	Yield
With Wilkinson's catalyst In water; acetonitrile for 2h; Heating;	65%

N-Chlor-N-aethyl-1-adamantanamin (34913-37-6) → 1-chloroadamantane (935-56-8) + 1-Adamantanamine (768-94-5) + 1-N-ethylaminoadamantane (3717-44-0)

Conditions	Yield
In dichloromethane at 250 - 260℃; 15-30percent SE-30 on Chromosorb W;	A 10% B 10% C 56%
In dichloromethane at 250 - 260℃; 15-30percent SE-30 on Chromosorb W;	A 10% B 10% C 56%

1-(Chloroamino)adamantane (24375-06-2) → 1-chloroadamantane (935-56-8) + 1-Adamantanamine (768-94-5)

Conditions	Yield
In dichloromethane at 250 - 260℃; 15-30percent SE-30 on Chromosorb W;	A 38% B 52%
In dichloromethane; water at 250 - 260℃; 15-30percent SE-30 on Chromosorb W;	A 38% B 52%

diethyl ether (60-29-7) + [Cl2NN]Cu-NHAd (1215209-26-9) → N-(1-adamantyl)imidoethane (98969-45-0) + 1-Adamantanamine (768-94-5)

Conditions	Yield
In n-heptane at 20℃; for 24h; Inert atmosphere;	A 44% B n/a

1-Adamantyl bromide (768-90-1) + diphenylphosphide ion (34676-89-6) → 1-Adamantanamine (768-94-5) + (1-adamantyl)diphenylphosphine (163311-93-1)

Conditions	Yield
With amide In ammonia for 2h; Product distribution; Irradiation; other haloadamantanes, other nucleophiles;	A 10% B 40%

methanol (67-56-1) + 1-Azidoadamantane (24886-73-5) → (1-adamantyl)dimethylamine (3717-40-6) + 1-Adamantanamine (768-94-5) + (1-adamantyl)(methyl)amine hydrochloride (3717-39-3)

Conditions	Yield
Stage #1: methanol; 1-Azidoadamantane With trans-RuCl(phenpyra-Me)(PPh3)2PF6; sodium hydroxide at 125℃; for 5h; Sealed tube; Inert atmosphere; Glovebox; Stage #2: With hydrogenchloride	A 26 %Chromat. B 10 %Chromat. C 35%

1-(Bromoamino)adamantane (5511-20-6) → 1-Adamantyl bromide (768-90-1) + 1-Adamantanamine (768-94-5)

Conditions	Yield
In dichloromethane at 250 - 260℃; 15-30percent SE-30 on Chromosorb W;	A 30% B n/a

N-Chlor-N-aethyl-1-adamantanamin (34913-37-6) → 1-Adamantanamine (768-94-5)

Conditions	Yield
In dichloromethane at 250 - 260℃; 15-30percent SE-30 on Chromosorb W;	10%

1-Azidoadamantane (24886-73-5) → 1-adamanthanol (768-95-6) + 1-Adamantanamine (768-94-5)

Conditions	Yield
With bromobenzene; magnesium Yield given. Multistep reaction;

adamantane-1-carboxamide (5511-18-2) → 1-Adamantanamine (768-94-5)

Conditions	Yield
With bis-[(trifluoroacetoxy)iodo]benzene In water; acetonitrile Ambient temperature;

1-nitroadamantane (7575-82-8) → 1-Adamantanamine (768-94-5) + N-adamantylhydroxylamine (31463-23-7)

Conditions	Yield
With sodium dithionite; potassium carbonate; 1,1′-dioctyl-4,4′-bipyridinium In water; acetonitrile at 35℃; for 2h; Yield given. Yields of byproduct given;

ethanol (64-17-5) + O-ethyl N-1-adamantylphosphoramidic acid (155051-57-3) → Diethyl phosphate (598-02-7) + 1-Adamantanamine (768-94-5)

Conditions	Yield
Heating; various solvents; thermal fragmentation of O-ethyl N-substituted phosphoramidothioates; possible mechanism;

N-(1-adamantyl)phenylphosphonamidic acid (182175-26-4) → 1-Adamantanamine (768-94-5) + phenyl dioxophosphorane (55861-16-0) + C22H27NO4P2*C10H17N

Conditions	Yield
In toluene at 64.5℃; for 0.133333h; Rate constant; Mechanism; thermal fragmentation, other reagents, other solvents;

carbon disulfide (75-15-0) + 1-Adamantanamine (768-94-5) → 1-adamantylisothiocyanate (4411-26-1)

Conditions	Yield
With dmap; di-tert-butyl dicarbonate; triethylamine	100%
With S,S'-bis(1-phenyl-1H-tetrazol-5-yl) dithiocarbonate; triethylamine In acetonitrile for 0.333333h;	95%
Stage #1: carbon disulfide; 1-Adamantanamine With triethylamine In ethanol at 0℃; for 1.5h; Stage #2: With dmap; di-tert-butyl dicarbonate In ethanol at 20℃; for 1h;	90%
Stage #1: carbon disulfide; 1-Adamantanamine With triethylamine In ethanol at 20℃; Stage #2: With dmap; di-tert-butyl dicarbonate In ethanol at 20℃; for 0.25h; Further stages.;	82%
With potassium hydroxide

1-Adamantanamine (768-94-5) + formic acid ethyl ester (109-94-4) → N-(1-adamantyl)formamide (3405-48-9)

Conditions	Yield
for 12h; Formylation; Heating;	100%
In dimethyl sulfoxide at 100℃; for 24h;
for 12h; Heating;
at 200 - 250℃; for 16h; Autoclave;
In chloroform for 48h; Reflux;

1-Adamantanamine (768-94-5) + benzaldehyde (100-52-7) → 2-[N-(1-adamantyl)]aminomethylbenzene (3717-60-0)

Conditions	Yield
With acetic acid In methanol at 20℃; for 48h;	100%
With triphenylborane; Dimethylphenylsilane In water; acetonitrile at 100℃; for 25h;	90%
With sodium cyanoborohydride In methanol at 20℃; Inert atmosphere;	71%
With sodium tris(acetoxy)borohydride; acetic acid In 1,2-dichloro-ethane for 24h;

1-Adamantanamine (768-94-5) + Fmoc-Tyr(tBu)-OH (71989-38-3) → (2S)-N-Adamantyl-3-[(4-tert-butoxy)phenyl]-2-(9-fluorenylmethoxycarbonylamino)propanamide (194673-21-7)

Conditions	Yield
With benzotriazol-1-ol; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide for 12h; Ambient temperature;	100%

1-Adamantanamine (768-94-5) + 3-Phenylpropionic acid (501-52-0) → N-((3s,5s,7s)-adamantan-1-yl)-3-phenylpropanamide

Conditions	Yield
Stage #1: 3-Phenylpropionic acid 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 at 20℃; for 0.166667h; Stage #2: 1-Adamantanamine at 20℃; for 1h;	100%
With dmap; 2-methyl-6-nitrobenzoic anhydride In dichloromethane at 20℃;	96%
Stage #1: 3-Phenylpropionic acid With 1,1'-carbonyldioxydi[2(1H)-pyridone] In dichloromethane at 20℃; for 1h; Stage #2: 1-Adamantanamine In dichloromethane at 20℃;	90%

diethyl [(diethylamino)ethynyl]phosphonate (5074-75-9) + 1-Adamantanamine (768-94-5) → diethyl [2-(1-adamantylamino)-2-(diethylamino)vinyl]phosphonate

Conditions	Yield
In toluene at 60℃;	100%

2,4-dichloro-7-methylthieno[3,2-d]pyrimidine (35265-83-9) + 1-Adamantanamine (768-94-5) → 4-(1-adamantylamino)-2-chloro-7-methylthieno[3,2-d]pyrimidine

Conditions	Yield
In water; N,N-dimethyl-formamide at 0 - 20℃; for 2h;	100%

[3-((2R)-2-{[(1R)-1-phenyl-ethyl]-amino}-propyl)-phenyl]-acetic acid (865589-88-4) + 1-Adamantanamine (768-94-5) → N-adamantan-1-yl-2-{3-[(R)-2-((R)-1-phenyl-ethylamino)-propyl]-phenyl}-acetamide (865589-89-5)

Conditions	Yield
With 2-chloro-1,3-dimethyl-2-imidazolinium hexafluorophosphate; triethylamine In dichloromethane at 20℃; for 2h;	100%
With DIP In tetrahydrofuran	82%
Stage #1: [3-((2R)-2-{[(1R)-1-phenyl-ethyl]-amino}-propyl)-phenyl]-acetic acid; 1-Adamantanamine In dichloromethane at 20℃; for 0.25h; Stage #2: With CIP In dichloromethane for 2h;

1-Adamantanamine (768-94-5) + N-(tert-butoxycarbonyl)-D-proline (37784-17-1) → tert-butyl (2R)-2-[(adamantan-1-yl)carbamoyl]pyrrolidine-1-carboxylate

Conditions	Yield
With 4-methyl-morpholine; dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃;	100%
With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In ethyl acetate at 20℃; for 72h;	96%

2,4-dichloro-7-methylthieno[3,2-d]pyrimidine (35265-83-9) + 1-Adamantanamine (768-94-5) → 4-(1-Adamantylamino)-2-chloro-7-methylthieno[3,2-d] pyrimidine (221043-49-8)

Conditions	Yield
In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; N,N-dimethyl-formamide	100%

1-Adamantanamine (768-94-5) → amantadine hydrochloride (665-66-7)

Conditions	Yield
With hydroxylamine hydrochloride In ethanol for 2h; Reflux;	100%
With hydrogenchloride In dichloromethane; water at 50℃; for 3h; Solvent; Temperature; Time;	96%
With hydrogenchloride In water; toluene at 0 - 20℃; for 1h; Product distribution / selectivity;
With hydrogenchloride In diethyl ether

ethyl 6-bromo-1,2-dihydro-4-hydroxy-2-oxo-1-pentylquinoline-3-carboxylate (1314230-91-5) + 1-Adamantanamine (768-94-5) → N-(adamantan-1-yl)-6-bromo-1,2-dihydro-4-hydroxy-2-oxo-1-pentylquinoline-3-carboxamide (1314230-78-8)

Conditions	Yield
In toluene for 1h; Inert atmosphere; Reflux;	100%

1-Adamantanamine (768-94-5) + (5-bromo-1H-indol-3-yl)-acetic acid (40432-84-6) → 2-(5-bromo-1H-indol-3-yl)-N-(adamantan-1-yl)acetamide (1378020-88-2)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 2h; Inert atmosphere;	100%

1-Adamantanamine (768-94-5) + C19H22O7 → C29H37NO6

Conditions	Yield
With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;	100%

1-Adamantanamine (768-94-5) + trimethylaluminum (75-24-1) → AlMe3(1-adamantylamine)

Conditions	Yield
In toluene at 20℃; for 1h;	100%

1-Adamantanamine (768-94-5) + (2,3,4,5-tetramethyl-1-(8-quinolyl)cyclopentadienyl)Y(AlMe4)2 → (2,3,4,5-tetramethyl-1-(8-quinolyl)cyclopentadienyl)YMe[NH(adamantyl)](AlMe3)

Conditions	Yield
In toluene at 20℃;	100%

1-Adamantanamine (768-94-5) + ethyl 1-pentyl-1,2-dihydro-4-hydroxy-2-oxo-quinoline-3-carboxylate (148237-79-0) → C25H32N2O3

Conditions	Yield
In toluene Reflux;	100%

1-Adamantanamine (768-94-5) + MECLOFENAMIC ACID (644-62-2) → C10H17N*C14H11Cl2NO2

Conditions	Yield
In methanol at 20℃;	100%

1-Adamantanamine (768-94-5) + tolfenamic Acid (13710-19-5) → C10H17N*C14H12ClNO2

Conditions	Yield
In methanol at 20℃;	100%

flufenamic acid (530-78-9) + 1-Adamantanamine (768-94-5) → C10H17N*C14H10F3NO2

Conditions	Yield
In methanol at 20℃;	100%

1-Adamantanamine (768-94-5) + [1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetic acid (53-86-1) → C19H16ClNO4*C10H17N

Conditions	Yield
In methanol at 20℃;	100%

1-Adamantanamine (768-94-5) + mefenamic Acid (61-68-7) → C10H17N*C15H15NO2

Conditions	Yield
In methanol at 20℃;	100%

[2-(2,6-dichloroanilino)phenyl]acetic acid (15307-86-5) + 1-Adamantanamine (768-94-5) → C10H17N*C14H11Cl2NO2

Conditions	Yield
In methanol at 20℃;	100%

1-Adamantanamine (768-94-5) + C24H23ClN2O6 → C24H23ClN2O6*C10H17N

Conditions	Yield
In methanol at 20℃;	100%

1-Adamantanamine (768-94-5) + Indo-Leu (87270-41-5) → C25H27ClN2O5*C10H17N

Conditions	Yield
In methanol at 20℃;	100%

1-Adamantanamine (768-94-5) + C24H25ClN2O5 → C24H25ClN2O5*C10H17N

Conditions	Yield
In methanol at 20℃;	100%

1-Adamantanamine (768-94-5) + (2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetyl)-L-alanine → C22H21ClN2O5*C10H17N

Conditions	Yield
In methanol at 20℃;	100%

1-Adamantanamine (768-94-5) + C23H23ClN2O6 → C23H23ClN2O6*C10H17N

Conditions	Yield
In methanol at 20℃;	100%

1-Adamantanamine (768-94-5) + (2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetyl)-L-phenylalanine (140225-92-9) → C28H25ClN2O5*C10H17N

Conditions	Yield
In methanol at 20℃;	100%

1-Adamantanamine (768-94-5) + C17H17ClN2O3 → C17H17ClN2O3*C10H17N

Conditions	Yield
In methanol at 20℃;	100%

Upstream product

• 768-90-1 1-Adamantyl bromide 
• 34676-89-6 diphenylphosphide ion 
• 24886-73-5 1-Azidoadamantane 
• 5511-18-2 adamantane-1-carboxamide 
• 24375-06-2 1-(Chloroamino)adamantane 
• 3667-65-0 1-adamantyl-diallylamine 
• 5511-20-6 1-(Bromoamino)adamantane 
• 34913-37-6 N-Chlor-N-aethyl-1-adamantanamin 
• 141903-89-1 Adamantan-1-yl-[2,2,2-trifluoro-1-phenyl-eth-(Z)-ylidene]-amine 
• 7575-82-8 1-nitroadamantane 
• 64-17-5 ethanol 
• 155051-57-3 O-ethyl N-1-adamantylphosphoramidic acid 
• 182175-26-4 N-(1-adamantyl)phenylphosphonamidic acid 
• 281-23-2 adamantane 

Downstream Products

• 37818-93-2 N-(adamantan-1-yl)ethane-1,2-diamine 
• 15004-38-3 N-(1-Adamantyl)-N'-(β-chlorethyl)-harnstoff 
• 42022-57-1 Methyl-N-(1-adamantyl)oxamat 
• 17822-61-6 N-Adamantyl-⁽¹⁾-N'-p-toluolsulfonyl-harnstoff 
• 20887-46-1 2-Aminobenzoesaeure-amid 
• 15784-82-4 N-(adamantan-1-yl)cyanamide 
• 31224-44-9 Adamantan-1-yl-[2,2,3,3,3-pentafluoro-prop-(Z)-ylidene]-amine 
• 62701-65-9 Adamantan-1-yl-[1-pentamethylphenyl-meth-(E)-ylidene]-amine 
• 49802-24-6 Diphenyl-N-1-adamantylphosphoramidat 
• 59747-75-0 4-(Adamantan-1-ylamino)-1-(4-methoxy-phenoxy)-butan-2-ol 
• 17822-64-9 N'-<4-Chlor-benzolsulfonyl>-N--harnstoff 
• 99998-83-1 N'-<4-Aethylmercapto-benzolsulfonyl>-N--harnstoff 
• 16309-28-7 N'-<4-Acetyl-benzolsulfonyl>-N--harnstoff 
• 31040-90-1 1-Adamantan-1-yl-3-(2-cyclohex-3-enyl-ethyl)-thiourea 

Relevant articles and documents

Synthesis, characterization, crystal structure, and electrochemical properties of three copper(II) complexes with 3,5-dihalosalicylaldehyde Schiff bases derived from amantadine

Complexes 1-3, C34H36X4CuN2O2 (X = Cl, Br, I), were synthesized with copper chloride dihydrate and three new Schiff base ligands derived from amantadine and 3,5-dihalosalicylaldehydes. They were characterized by IR, UV–VIS, elemental analysis, molar conductance, and single-crystal X-ray diffraction. Single-crystal X-ray diffraction analysis reveals that 1 and 2 crystallize in the triclinic system, Pī space group. Each asymmetric unit consists of one copper(II) ion, two corresponding deprotonated Schiff base ligands and one lattice dichloromethane molecule. 3 crystallizes in the monoclinic system, P21/n space group. Each asymmetric unit consists of one copper(II) ion and two deprotonated iodo- Schiff base ligands. The tetra-coordination of the central copper(II) ion in 1-3 is constructed by two nitrogen atoms and two oxygen atoms from the corresponding Schiff base ligands, forming a distorted tetrahedral geometry. Electrochemical properties of the complexes were determined by cyclic voltammetry. (Figure presented.).

Synthesis, characterization, and antibacterial activity of two zinc(II) complexes with Schiff bases from halogenated salicylaldehyde and amantadine

By a condensation reaction of halogenated salicylaldehyde and amantadine, two new Schiff base ligands (HL1 and HL2) were synthesized, respectively. A followed mixture of the ligands and zinc(II) chloride in the presence of NaOH in an alcoholic medium brought out two novel complexes (ZnL2 1) (I) and (ZnL2 2 (II). These two complexes were characterized by the means of melting point, elemental analysis, IR, UV-Vis, 1H NMR, molar conductance and single-crystal X-ray diffraction analysis. X-ray diffraction analysis reveals that I crystallizes in monoclinic system, P21/c space group, a = 9.7812(5), b = 25.6198(12), c = 27.7381(18) A, β = 105.881(4), F(000) = 1416, R1 = 0.0731, wR2 = 0.1147; II crystallizes in orthorhombic system, Pbca space group, a = 11.1717(10), b = 20.5888(15), c = 27.7381(18) A, F(000) = 2976, R1 = 0.1341, wR2 = 0.1410. Both in I and II, the central zinc(II) atom is four-coordinated via two nitrogen atoms and two oxygen atoms from the corresponding Schiff base ligands, forming a distorted tetrahedral geometry.

High-relaxivity magnetic resonance imaging (MRI) contrast agent based on supramolecular assembly between a gadolinium chelate, a modified dextran, and poly-β-cyclodextrin

Nanosized contrast agents have great potential in magnetic resonance molecular imaging applications for clinical diagnosis. This study proposes new nanoparticles spontaneously formed under mild conditions and composed of a noncovalent adduct between a gadolinium complex, a polymer of β-cyclodextrin (pβCD: MW 1.5×106 g mol-1) and a dextran grafted with alkyl chains (MD). The formation of this supramolecular nanoassembly is based upon a "lock-and-key" recognition process in which the hydrophobic alkyl chains of MD and the adamantyl moieties of macrocyclic GdIII chelates are included in the cavities of pβCD. The large number of βCDs contained in the pβCD resulted in the formation of 200 nm diameter nanoparticles, each entrapping 1.8 × 105 molecules of a low-molecular-weight Gd complex. This system, which exhibits a great relaxivity enhancement (48.4 mw-1 s -1, at 20MHz and 37°C) compared to the GdIII chelate itself (5.2 mM-1 s-1), appears to be a promising strategy for the in vivo targeted delivery of GdIII complexes. The mechanisms of particle formation, conjugation strategies, and relaxometric characterizations in the field of contrast-enhanced magnetic resonance imaging are discussed.

Comparative proton nuclear magnetic resonance studies of amantadine complexes formed in aqueous solutions with three major cyclodextrins

Host-guest complexes of alpha-, beta-, and gamma-cyclodextrins (α-CD, β-CD, and γ-CD, respectively) with amantadine (1-aminoadamantane, AMA; an antiviral agent) were characterized in aqueous solutions using proton nuclear magnetic resonance (NMR) spectroscopy. Host-guest molecular interactions were manifested by changes in the chemical shifts of AMA protons. NMR Job's plots showed that the stoichiometry of all the studied complexes was 1:1. Two-dimensional T-ROESY experiments demonstrated that the complexes were formed by different degrees of incorporation of the adamantyl group of AMA into the CD cavity. The mode of AMA binding was proposed. The AMA molecule came into the α-CD cavity (the smallest size) or β-CD cavity (the intermediate size) through its wide entrance to become shallowly or deeply accommodated, respectively. In the complex of AMA with γ-CD (the largest cavity size), the adamantyl group was also quite deeply inserted into the CD cavity, but it arrived there through the narrow cavity entrance. It was found that the adamantyl group of AMA was best accommodated by the β-CD cavity. The binding constants Kaa of the studied complexes (in M-1), determined from DOSY NMR, were fairly high; their values in an ascending order were: α-CD (183) γ-CD (306) a?‰β-CD (5150). 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:274-282, 2014

Characterization and solution properties of adamantane-containing quaternary-ammonium-salt-type amphiphilic ionic liquids

Quaternary-ammonium-salt-type amphiphilic compounds ([CnAdA][X], where n represents the alkyl chain length (n = 1, 2, 4, 6, 8, or 10), X represents a counterion such as [BF4]?, [PF6]?, trifluoromethanesulfonate ([OTf]?), bis(fluorosulfonyl)amide ([FSA]?), or bis(trifluoromethanesulfonyl)amide ([NTf2]?), and Ad and A of AdA represent the adamantane structure and quaternary ammonium group, respectively) were synthesized. The melting points of the prepared compounds were determined by differential scanning calorimetry, and the derivatives with melting points lower than 100 °C were classified as ionic liquids for subsequent analyses. The amphiphilic ionic liquids, [CnAdA][NTf2] (n = 6 and 8), exhibited the lowest melting points (30.6 and 38.7 °C, respectively). Further, the [CnAdA][NTf2] series of amphiphilic ionic liquids exhibited significantly lower conductivities and higher viscosities than the corresponding ionic liquids without the adamantane moiety, [Cn][NTf2]. The viscosities of [CnAdA][NTf2] (n = 6 and 8) decreased significantly with increasing temperature, and showed a larger temperature dependence than that of the viscosities of the [Cn][X] series. The amphiphilic ionic liquids, [C8AdA][X] readily adsorbed at the air/water interface and oriented themselves but did not show the critical micelle concentration in the concentration range over which they could be dissolved in water. The amphiphilic ionic liquids and compounds tended to form ion pairs or premicelles, such as dimers or trimers, in aqueous solutions.

The first N-alkyl-N′-polyfluorohetaryl sulfur diimide

The first Alk-N=S=N-HetF sulfur diimide 6 (Alk = adamant-1-yl, HetF = 2,3,5,6-tetrafluoropyrid-4-yl) was prepared by trapping of the corresponding alkylthiazylamide [AlkNSN]-3 with pentafluoropyridine, followed by X-ray st

Method for synthesizing and preparing amantadine dry product

The invention discloses a synthesis and preparation method of an amantadine dry product, and relates to the technical field of amantadine preparation. The method mainly comprises adamantane, nitrogendioxide, ozone, hydrazine hydrate, ethanol, diethyl ether, ferric chloride hexahydrate and activated carbon, and comprises the following steps: synthesis of a nitro compound: adding adamantane and dichloromethane into a flask according to a ratio of 1g: 120ml, stirring at a certain temperature, introducing 30 equivalents of nitrogen dioxide under a certain condition, introducing ozone at a low speed, reacting for 30 minutes, adding a sodium bicarbonate solution, washing the organic phase to be neutral, performing drying, and carrying out rotary evaporation to obtain the product 1-nitro adamantane. The dry amantadine product is prepared through a hydrazine hydrate reduction method, corresponding purification is conducted, the whole reaction process is mild, the process steps are simple andconvenient, the requirement for equipment is simple, the conversion rate is very high, and the method has the value of industrial batch production popularization.

Method for preparing amine through catalytic reduction of nitro compound by cyclic (alkyl) (amino) carbene chromium complex

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Preparation method of amantadine

The invention discloses a preparation method of amantadine, which belongs to the technical field of organic chemical synthesis, and is characterized by comprising the following steps: taking a compound adamantane as an initial raw material, generating an intermediate 1-acetamido adamantane in the presence of acetonitrile, a polyion liquid PIL catalyst and sulfuric acid, and then hydrolyzing the intermediate into amantadine in a system of alcohol and alkali. The preparation method is environment-friendly, post-treatment is convenient, the use amount of sulfuric acid and acetonitrile is greatly reduced through the catalyst polyion liquid, and post-treatment is simple. The ionic liquid catalyst can be recycled, so that the cost is greatly saved, and the method is suitable for large-scale industrial production.

The benzyl can be selectively removed by visible light or near visible light. Method for protecting allyl and propargyl group

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