778-09-6

Usage

Uses

An analogue of Adamantane.

InChI:InChI=1/C13H21NO/c1-9(15)14-13-6-10-3-11(7-13)5-12(2,4-10)8-13/h10-11H,3-8H2,1-2H3,(H,14,15)

Synthetic route

1-bromo-3-methyladamantane (702-77-2) + acetonitrile (75-05-8) → 1-acetamido-3-methyltricyclo[3.3.1.13,7]decane (778-09-6)

Conditions	Yield
With sulfuric acid at 20℃; for 12h; Ritter Amidation;	90%
With sulfuric acid
Stage #1: 1-bromo-3-methyladamantane; acetonitrile With phosphoric acid at 20 - 87℃; for 18.5h; Stage #2: With sodium hydroxide; water; butan-1-ol In toluene at 20 - 45℃; pH=6 - 7;

1-methyl-adamantane (768-91-2) + acetonitrile (75-05-8) → 1-acetamido-3-methyltricyclo[3.3.1.13,7]decane (778-09-6)

Conditions	Yield
Stage #1: 1-methyl-adamantane With sulfuric acid; nitric acid at 0℃; for 6h; Stage #2: acetonitrile at 0℃; for 6h; Ritter-type reaction; Further stages.;	41.6%
(anodic oxidation);

acetamide (60-35-5) + 1-methyl-adamantane (768-91-2) → 1-acetamido-3-methyltricyclo[3.3.1.13,7]decane (778-09-6)

Conditions	Yield
With nitric acid at 120℃; for 2h;	70%

3,7-dimethylenebicyclo[3.3.1]nonane (770-14-9) + acetylium tetrafluoroborate (2261-02-1) + acetonitrile (75-05-8) → 1-acetamido-3-methyltricyclo[3.3.1.13,7]decane (778-09-6) + 1-acetonyl-3-acetylaminoadamantane (118647-96-4)

Conditions	Yield
In dichloromethane at -40℃; for 0.25h;	A 15% B 75%

3-methyl-1-adamantanol (702-81-8) → 1-acetamido-3-methyltricyclo[3.3.1.13,7]decane (778-09-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / Ph3P, Br2 / acetonitrile / 30 h / Heating 2: 78 percent / Heating View Scheme

acetamide (60-35-5) + 1-bromo-3-methyladamantane (702-77-2) → 1-acetamido-3-methyltricyclo[3.3.1.13,7]decane (778-09-6)

Conditions	Yield
Heating;	78%

3-methyl-1-adamantanol nitrate (101974-65-6) + acetonitrile (75-05-8) → 1-acetamido-3-methyltricyclo[3.3.1.13,7]decane (778-09-6)

Conditions	Yield
With sulfuric acid for 3h;	75.8%

1-methyl-adamantane (768-91-2) → 1-acetamido-3-methyltricyclo[3.3.1.13,7]decane (778-09-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: Br2 2: H2SO4 View Scheme
Multi-step reaction with 2 steps 1: bromine / 20 °C / Reflux 2: sulfuric acid / 12 h / 20 °C View Scheme

3,7-dimethylenebicyclo[3.3.1]nonane (770-14-9) + acetonitrile (75-05-8) → 1-acetamido-3-methyltricyclo[3.3.1.13,7]decane (778-09-6)

Conditions	Yield
With sulfuric acid

Upstream product

• 770-14-9 3,7-dimethylenebicyclo[3.3.1]nonane 
• 2261-02-1 acetylium tetrafluoroborate 
• 75-05-8 acetonitrile 
• 768-91-2 1-methyl-adamantane 
• 702-81-8 3-methyl-1-adamantanol 
• 101974-65-6 3-methyl-1-adamantanol nitrate 
• 60-35-5 acetamide 
• 702-77-2 1-bromo-3-methyladamantane 

Downstream Products

• 99998-84-2 N'--N-<3-methyl-adamantyl>-harnstoff 
• 78056-28-7 3-methyl-1-aminoadamantane 

Relevant academic research and scientific papers

Synthesis and biological evaluation of memantine nitrates as a potential treatment for neurodegenerative diseases

A series of memantine nitrate derivatives, as dual functional compounds with neuroprotective and vasodilatory activity for neurodegenerative diseases, was designed and synthesized. These compounds combined the memantine skeleton and a nitrate moiety, and thus inhibited the N-methyl-d-aspartic acid receptor and released NO in the central nervous system. The biological evaluation results revealed that the new memantine nitrates were effective in protecting neurons against glutamate-induced injury in vitro. Moreover, memantine nitrates dilated aortic rings against phenylephrine-induced contraction. The structure-activity relationships of neuroprotection and vasodilation were both analyzed. In further studies, compound MN-05 significantly protected cortical neurons by inhibiting Ca2+ influx, reducing free radical production and maintaining the mitochondrial membrane potential. Further research on MN-05 is warranted.

γ-aminoadamantanecarboxylic acids through direct C-H bond amidations

Utilizing bromine-free, direct C-H bond amidations we have synthesized a large variety of adamantane amides. Depending on the precursors used these amides directly yield pharmaceutically active aminoadamantanes or γ-aminoadamantanecarboxylic acids after hydrolytic cleavage. These rigid analogues of γ-aminobutyric acid (GABA) were protected at the C- and N-termini and we synthesized a number of peptides incorporating γ-aminoadamantanecarboxylic acids in solution as well as via solid phase peptide synthesis. These peptides are promising scaffolds for applications in medicinal chemistry as well as in organocatalysis. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.

PROCESS FOR PREPARING MEMANTINE HYDROCHLORIDE SUBSTANTIALLY FREE OF IMPURITIES

The present invention encompasses processes for preparing Memantine hydrochloride and its derivatives, substantially free of impurities.

Structure-Anti-Parkinson Activity Relationships in the Aminoadamantanes. Influence of Bridgehead Substitution

A limited series of bridgehead alkyl-, dialkyl- and trialkyl-substituted amantadines was synthesized and tested for potential anti-Parkinson activity as dopamine (DA) agonists.The compounds were evaluated using a battery of three murine bioassays, including stimulation of locomotor activity, induction of circling in animals with unilateral striatal lesions, and reversal of reserpine/α-methyltyrosine induced akinesia.Apparent mechanistic differences were seen between the methyl-substituted series and the ethyl-substituted series.While activities in both series increase with increasing liphophilicity, the methyl series (1b-d), as well as amantadine itself (1a) exhibits only indirect DA agonist activity, as evidenced by ipsilateral rotation in the circling model and no significant difference from control in reversal of akinesia.The ethyl series (1e,f) exhibits weak but reprodicible direct DA agonist activity, as shown by contralateral rotation in the circling assay for 1e and reversal of akinesia by 1e and 1f.The 3-n-propyl derivative (1g) was devoid of any DA agonist activity.