457068-92-7

Basic information

• Product Name: 1,3,3,5,5-pentamethylcyclohexylamine methanesulfonate
• Synonyms: 1,3,3,5,5-pentamethylcyclohexylamine methanesulfonate;neramexane mesylate;USAN 2000-2004;1,3,3,5,5-pentaMethylcyclohexanaMine Methanesulfonate
• CAS NO: 457068-92-7
• Molecular Formula: CH₄O₃S*C₁₁H₂₃N
• Molecular Weight: 265
• Product Categories: NMDA receptor antagonist
• Mol File: 457068-92-7.mol
• Article Data: 3

Chemical Properties

• Appearance: /
• CAS DataBase Reference: 1,3,3,5,5-pentamethylcyclohexylamine methanesulfonate(CAS DataBase Reference)
• NIST Chemistry Reference: 1,3,3,5,5-pentamethylcyclohexylamine methanesulfonate(457068-92-7)
• EPA Substance Registry System: 1,3,3,5,5-pentamethylcyclohexylamine methanesulfonate(457068-92-7)

Safety Data

• Hazardous Substances Data: 457068-92-7(Hazardous Substances Data)

Synthetic route

3,5,5-Trimethylcyclohex-2-en-1-one (78-59-1) → Neramexane mesylate (457068-92-7)

Conditions	Yield
Multi-step reaction with 5 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 5.1: ethyl acetate / 1 h / 0 - 5 °C View Scheme
Multi-step reaction with 5 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 5.1: ethyl acetate / 1 h / 0 - 5 °C View Scheme

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

3,3,5,5-tetramethylcyclohexanone (14376-79-5) → Neramexane mesylate (457068-92-7)

Conditions	Yield
Multi-step reaction with 4 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 4.1: ethyl acetate / 1 h / 0 - 5 °C View Scheme
Multi-step reaction with 4 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 4.1: ethyl acetate / 1 h / 0 - 5 °C View Scheme

1,3,3,5,5-pentamethylcyclohexanol (38490-33-4) → Neramexane mesylate (457068-92-7)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sulfuric acid / acetic acid / 1 h / 5 - 10 °C 2.1: hydrogenchloride; thiourea / water / 6 h / Reflux 2.2: pH 7 3.1: ethyl acetate / 1 h / 0 - 5 °C View Scheme

N-Chloroacetyl-1,3,3,5,5-pentamethylcyclohexanamine (316364-93-9) → Neramexane mesylate (457068-92-7)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: hydrogenchloride; thiourea / water / 6 h / Reflux 1.2: pH 7 2.1: ethyl acetate / 1 h / 0 - 5 °C View Scheme

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

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

Neramexane mesylate (457068-92-7) → neramexane stearate

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide / water / 20 °C 2: dichloromethane / 2 h / 20 °C View Scheme

Neramexane mesylate (457068-92-7) → neramexane undecylenate

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide / water / 20 °C 2: neat (no solvent) / 20 °C / Cooling View Scheme

Neramexane mesylate (457068-92-7) → neramexane oleate

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide / water / 20 °C 2: neat (no solvent) / 20 °C / Cooling View Scheme

Upstream product

• 316364-93-9 N-Chloroacetyl-1,3,3,5,5-pentamethylcyclohexanamine 
• 38490-33-4 1,3,3,5,5-pentamethylcyclohexanol 
• 14376-79-5 3,3,5,5-tetramethylcyclohexanone 
• 75-75-2 methanesulfonic acid 
• 219810-59-0 neramexane 
• 78-59-1 3,5,5-Trimethylcyclohex-2-en-1-one 

Downstream Products

• 219810-59-0 neramexane 

Relevant articles and documents

SYNTHESIS OF 1-AMINO-1,3,3,5,5,-CYCLOHEXANE MESYLATE

Process for manufacturing 1-amino-1,3,3,5,5-pentamethylcyclohexane mesylate comprising step (i): (i) reacting 1-amino-1,3,3,5,5-pentamethylcyclohexane with methane sulfonic acid in a solvent or a mixture of two or more solvents selected from anisole, cumene, pentane, hexane, heptane, isooctane, methyl acetate, propyl acetate, isopropyl acetate, n-butyl acetate, isobutyl acetate, methyl ethyl ketone, methyl isopropylketone, methyl isobutyl ketone, dimethyl sulphoxide, tetrahydrofuran, methyltetrahydrofuran, 1,1-diethoxypropane, 1,1-dimethoxymethane, and 2,2-dimethoxypropane.

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.