219810-59-0

Basic information

• Product Name: NERAMEXANE
• Synonyms: NERAMEXANE
• CAS NO: 219810-59-0
• Molecular Formula: C₁₁H₂₃N
• Molecular Weight: 169.31
• Mol File: 219810-59-0.mol
• Article Data: 12

Chemical Properties

• Boiling Point: 195.5°Cat760mmHg
• Flash Point: 39.7°C
• Appearance: /
• Density: 0.809g/cm³
• Vapor Pressure: 0.417mmHg at 25°C
• Refractive Index: 1.433
• CAS DataBase Reference: NERAMEXANE(CAS DataBase Reference)
• NIST Chemistry Reference: NERAMEXANE(219810-59-0)
• EPA Substance Registry System: NERAMEXANE(219810-59-0)

Safety Data

• Hazardous Substances Data: 219810-59-0(Hazardous Substances Data)

Usage

Uses

Treatment of depression, Alzheimer’s disease, and pain.

InChI:InChI=1/C11H23N/c1-9(2)6-10(3,4)8-11(5,12)7-9/h6-8,12H2,1-5H3

Synthetic route

Neramexane mesylate (457068-92-7) → neramexane (219810-59-0)

Conditions	Yield
With sodium hydroxide In water at 20℃;	100%

N-Chloroacetyl-1,3,3,5,5-pentamethylcyclohexanamine (316364-93-9) → neramexane (219810-59-0)

Conditions	Yield
Stage #1: N-Chloroacetyl-1,3,3,5,5-pentamethylcyclohexanamine With hydrogenchloride; thiourea In water for 6h; Reflux; Stage #2: With sodium hydroxide In water pH=7;	89%
With acetic acid; thiourea In ethanol for 10h; Substitution; Heating;
Stage #1: N-Chloroacetyl-1,3,3,5,5-pentamethylcyclohexanamine With hydrogenchloride; thiourea In water for 6h; Reflux; Stage #2: With sodium hydroxide In water pH=7;
Stage #1: N-Chloroacetyl-1,3,3,5,5-pentamethylcyclohexanamine With hydrogenchloride; thiourea In water for 6h; Reflux; Stage #2: With sodium hydroxide In water pH=7; Product distribution / selectivity;

1-azido-1,3,3,5,5-pentamethyl-cyclohexane → neramexane (219810-59-0)

Conditions	Yield
With lithium aluminium tetrahydride In diethyl ether at 20℃; for 5h; Reduction;

1,3,3,5,5-pentamethylcyclohexanol (38490-33-4) → neramexane (219810-59-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 86 percent / AcOH; H2SO4 / 5 h / 20 °C 2: thiourea; AcOH / ethanol / 10 h / Heating View Scheme
Multi-step reaction with 2 steps 1: 67 percent / HN3; TiCl4 / CHCl3 / 24 h / 20 °C 2: LiAlH4 / diethyl ether / 5 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1.1: sulfuric acid / acetic acid / 1 h / 5 - 10 °C 2.1: hydrogenchloride; thiourea / water / 6 h / Reflux 2.2: pH 7 View Scheme

3,3,5,5-tetramethylcyclohexanone (14376-79-5) → neramexane (219810-59-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 93 percent / diethyl ether / 1 h / 20 °C 2: 67 percent / HN3; TiCl4 / CHCl3 / 24 h / 20 °C 3: LiAlH4 / diethyl ether / 5 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: tetrahydrofuran / 5 - 15 °C 2.1: sulfuric acid / acetic acid / 1 h / 5 - 10 °C 3.1: hydrogenchloride; thiourea / water / 6 h / Reflux 3.2: pH 7 View Scheme
Multi-step reaction with 3 steps 1.1: tetrahydrofuran / 1 h / 5 - 15 °C 2.1: sulfuric acid / acetic acid / 1 h / 5 - 10 °C 3.1: hydrogenchloride; thiourea / water / 6 h / Reflux 3.2: pH 7 View Scheme

3,5,5-Trimethylcyclohex-2-en-1-one (78-59-1) → neramexane (219810-59-0)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: copper(l) iodide; lithium chloride / tetrahydrofuran / 1 h / 5 - 15 °C 2.1: tetrahydrofuran / 5 - 15 °C 3.1: sulfuric acid / acetic acid / 1 h / 5 - 10 °C 4.1: hydrogenchloride; thiourea / water / 6 h / Reflux 4.2: pH 7 View Scheme
Multi-step reaction with 4 steps 1.1: copper(l) iodide; lithium chloride / tetrahydrofuran / 1 h / 5 - 15 °C 2.1: tetrahydrofuran / 1 h / 5 - 15 °C 3.1: sulfuric acid / acetic acid / 1 h / 5 - 10 °C 4.1: hydrogenchloride; thiourea / water / 6 h / Reflux 4.2: pH 7 View Scheme

Neramexane mesylate (457068-92-7) → neramexane (219810-59-0)

Conditions	Yield
With sodium hydroxide In water at 20℃;	100%

N-Chloroacetyl-1,3,3,5,5-pentamethylcyclohexanamine (316364-93-9) → neramexane (219810-59-0)

Conditions	Yield
Stage #1: N-Chloroacetyl-1,3,3,5,5-pentamethylcyclohexanamine With hydrogenchloride; thiourea In water for 6h; Reflux; Stage #2: With sodium hydroxide In water pH=7;	89%
With acetic acid; thiourea In ethanol for 10h; Substitution; Heating;
Stage #1: N-Chloroacetyl-1,3,3,5,5-pentamethylcyclohexanamine With hydrogenchloride; thiourea In water for 6h; Reflux; Stage #2: With sodium hydroxide In water pH=7;
Stage #1: N-Chloroacetyl-1,3,3,5,5-pentamethylcyclohexanamine With hydrogenchloride; thiourea In water for 6h; Reflux; Stage #2: With sodium hydroxide In water pH=7; Product distribution / selectivity;

1-azido-1,3,3,5,5-pentamethyl-cyclohexane → neramexane (219810-59-0)

Conditions	Yield
With lithium aluminium tetrahydride In diethyl ether at 20℃; for 5h; Reduction;

1,3,3,5,5-pentamethylcyclohexanol (38490-33-4) → neramexane (219810-59-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 86 percent / AcOH; H2SO4 / 5 h / 20 °C 2: thiourea; AcOH / ethanol / 10 h / Heating View Scheme
Multi-step reaction with 2 steps 1: 67 percent / HN3; TiCl4 / CHCl3 / 24 h / 20 °C 2: LiAlH4 / diethyl ether / 5 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1.1: sulfuric acid / acetic acid / 1 h / 5 - 10 °C 2.1: hydrogenchloride; thiourea / water / 6 h / Reflux 2.2: pH 7 View Scheme

3,3,5,5-tetramethylcyclohexanone (14376-79-5) → neramexane (219810-59-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 93 percent / diethyl ether / 1 h / 20 °C 2: 67 percent / HN3; TiCl4 / CHCl3 / 24 h / 20 °C 3: LiAlH4 / diethyl ether / 5 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: tetrahydrofuran / 5 - 15 °C 2.1: sulfuric acid / acetic acid / 1 h / 5 - 10 °C 3.1: hydrogenchloride; thiourea / water / 6 h / Reflux 3.2: pH 7 View Scheme
Multi-step reaction with 3 steps 1.1: tetrahydrofuran / 1 h / 5 - 15 °C 2.1: sulfuric acid / acetic acid / 1 h / 5 - 10 °C 3.1: hydrogenchloride; thiourea / water / 6 h / Reflux 3.2: pH 7 View Scheme

3,5,5-Trimethylcyclohex-2-en-1-one (78-59-1) → neramexane (219810-59-0)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: copper(l) iodide; lithium chloride / tetrahydrofuran / 1 h / 5 - 15 °C 2.1: tetrahydrofuran / 5 - 15 °C 3.1: sulfuric acid / acetic acid / 1 h / 5 - 10 °C 4.1: hydrogenchloride; thiourea / water / 6 h / Reflux 4.2: pH 7 View Scheme
Multi-step reaction with 4 steps 1.1: copper(l) iodide; lithium chloride / tetrahydrofuran / 1 h / 5 - 15 °C 2.1: tetrahydrofuran / 1 h / 5 - 15 °C 3.1: sulfuric acid / acetic acid / 1 h / 5 - 10 °C 4.1: hydrogenchloride; thiourea / water / 6 h / Reflux 4.2: pH 7 View Scheme

para-dodecylbenzenesulfonic acid (121-65-3) + neramexane (219810-59-0) → neramexane 4-dodecylbenzene sulfonate

Conditions	Yield
at 20℃; Cooling;	100%

10-undecenoic acid (112-38-9) + neramexane (219810-59-0) → neramexane undecylenate

Conditions	Yield
In neat (no solvent) at 20℃; Cooling;	100%

cis-Octadecenoic acid (112-80-1) + neramexane (219810-59-0) → neramexane oleate

Conditions	Yield
In neat (no solvent) at 20℃; Cooling;	100%

ammonium tetrathiomonomolybdate + neramexane (219810-59-0) → bis(1-ammonium-1,3,3,5,5-pentamethylcyclohexane) tetrathiomolybdate

Conditions	Yield
In water; isopropyl alcohol at 20 - 25℃; for 0.5h;	95%

stearic acid (57-11-4) + neramexane (219810-59-0) → neramexane stearate

Conditions	Yield
In dichloromethane at 20℃; for 2h;	90%

Br(1-)*C18H26NO6(1+) (952431-22-0) + neramexane (219810-59-0) → {3-benzyloxycarbonyl-(R)-2-[3-(1,3,3,5,5-pentamethyl-cyclohexylcarbamoyl)-propionyloxy]-propyl}-trimethylammonium bromide

Conditions	Yield
With dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 2h;	28%

L-carnitine isobutyric ester (952431-17-3) + neramexane (219810-59-0) → L-carnitine isobutyric ester

Conditions	Yield
With dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 2h;	19%

methanesulfonic acid (75-75-2) + neramexane (219810-59-0) → Neramexane mesylate (457068-92-7)

Conditions	Yield
In ethyl acetate at 0 - 5℃; for 1h;
In ethyl acetate at 0 - 5℃; for 1h;
In butanone

neramexane (219810-59-0) → neramexane hydrochloride

Conditions	Yield
With hydrogenchloride In butanone Product distribution / selectivity;

Upstream product

• 457068-92-7 Neramexane mesylate 
• 78-59-1 3,5,5-Trimethylcyclohex-2-en-1-one 
• 14376-79-5 3,3,5,5-tetramethylcyclohexanone 
• 38490-33-4 1,3,3,5,5-pentamethylcyclohexanol 
• 316364-93-9 N-Chloroacetyl-1,3,3,5,5-pentamethylcyclohexanamine 

Downstream Products

• 457068-92-7 Neramexane mesylate 
• 209185-99-9 neramexane hydrochloride 

Relevant articles and documents

NERAMEXANE SALTS

This invention relates to novel salts of 1-amino-1,3,3,5,5-pentamethylcyclohexane (Neramexane).

METHOD OF PREPARING NERAMEXANE

Method of preparing 1-amino-1,3,3,5,5-pentamethylcyclohexane or a pharmaceutically acceptable salt thereof, comprising at least two steps selected from the following steps (i) to (iv): (i) converting isophorone to 3,3,5,5-tetramethylcyclohexanone in the presence of methylmagnesium chloride; (N) converting 3,3,5,5-tetramethylcyclohexanone to 1-hydroxy-1,3,3,5,5- pentamethylcyclohexane in the presence of methylmagnesium chloride; (iii) converting 1-hydroxy-1,3,3,5,5-pentamethylcyclohexane to 1-chloroacetamido- 1,3,3,5,5-pentamethylcyclohexane in the presence of chloroacetonitrile in acidic solution; (iv) converting 1-chloroacetamido-1,3,3,5,5-pentamethylcyclohexane to 1-amino- 1,3,3,5,5-pentamethylcyclohexane in the presence of thiourea in water.

Novel treatment for alzheimer's disease

The present invention concerns a new pharmaceutical composition comprising an antagonist and a co-agonist of the N-methyl-D-aspartate-type glutamate receptor (NMDAR). The inventors found that the co-administration of these two compounds effectively inhibits production of amyloide-β peptide. In patient's suffering from Alzheimer's disease, these peptides are deposited in the extracellular matrix forming neuritic "plaques". Therefore, the present inventors identified a new possibility for prophylaxis and/or treatment of Alzheimer's disease by stopping the continued formation of neuropathological extracellular deposits.