3613-73-8

Basic information

• Product Name: dimebolin
• Synonyms: dimebolin;2,3,4,5-Tetrahydro-2,8-dimethyl-5-[2-(6-methyl-3-pyridinyl)ethyl]-1H-pyrido[4,3-b]indole;2,3,4,5-Tetrahydro-2,8-dimethyl-5-[2-(6-methyl-3-pyridyl)ethyl]-1H-pyrido[4,3-b]indole;Dimeboline;Dimebone;Preparation-84;dimebon;2,3,4,5-Tetrahydro-2,8-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-1H-pyrido[4,3-b]indole
• CAS NO: 3613-73-8
• Molecular Formula: C₂₁H₂₅N₃
• Molecular Weight: 319.44
• EINECS: 1312995-182-4
• Mol File: 3613-73-8.mol

Chemical Properties

• Melting Point: 115-116 °C
• Boiling Point: 448.46°C (rough estimate)
• Flash Point: 259.7 °C
• Appearance: White powder
• Density: 1.13
• Vapor Pressure: 2.37E-10mmHg at 25°C
• Refractive Index: 1.6380 (estimate)
• Solubility: ≤30mg/ml in ethanol;1mg/ml in DMSO;3mg/ml in dimethyl formamide
• PKA: 9.05±0.20(Predicted)
• CAS DataBase Reference: dimebolin(CAS DataBase Reference)
• NIST Chemistry Reference: dimebolin(3613-73-8)
• EPA Substance Registry System: dimebolin(3613-73-8)

Safety Data

• Hazardous Substances Data: 3613-73-8(Hazardous Substances Data)

Usage

InChI:InChI=1/C21H25N3/c1-15-4-7-20-18(12-15)19-14-23(3)10-9-21(19)24(20)11-8-17-6-5-16(2)22-13-17/h4-7,12-13H,8-11,14H2,1-3H3

Synthetic route

2-methyl-5-vinylpyridine (140-76-1) + 2.8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (19686-05-6) → dimebon (3613-73-8)

Conditions	Yield
With potassium phosphate In ISOPROPYLAMIDE at 100℃; for 24h; Inert atmosphere;	80%
With potassium hydroxide In 1-methyl-pyrrolidin-2-one at 100℃;	55%
With potassium hydroxide In diethylene glycol dimethyl ether at 120℃; for 42h; Product distribution / selectivity;	52%
With sodium ethanolate; sodium In dimethyl sulfoxide at 90 - 95℃;
With potassium phosphate In ISOPROPYLAMIDE at 130℃;

tert-butyl 8-methyl-5-(2-(6-methylpyridin-3-yl)ethyl)-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate (1227258-81-2) → dimebon (3613-73-8)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran for 2h; Reflux;	70%

1-Methyl-4-piperidone (1445-73-4) + 2-methyl-5-{2-[1-(4-methylphenyl)hydrazinyl]ethyl}pyridine (21241-08-7) → dimebon (3613-73-8)

Conditions	Yield
With acetic acid In water at 20℃; for 4h; Inert atmosphere; Reflux;
With hydrogenchloride In isopropyl alcohol for 0.25h;

N'-(1-methyl-piperidin-4-ylidene)-N-[2-(6-methyl-pyridin-3-yl)-ethyl]-N-p-tolyl-hydrazine (1229621-60-6) → dimebon (3613-73-8)

Conditions	Yield
With hydrogenchloride In ethanol; water at 100℃; for 0.5h;
Stage #1: N'-(1-methyl-piperidin-4-ylidene)-N-[2-(6-methyl-pyridin-3-yl)-ethyl]-N-p-tolyl-hydrazine With hydrogenchloride; water In ethanol at 80℃; for 1.5h; Stage #2: With sodium hydroxide In ethanol; water pH=14;
Stage #1: N'-(1-methyl-piperidin-4-ylidene)-N-[2-(6-methyl-pyridin-3-yl)-ethyl]-N-p-tolyl-hydrazine With hydrogenchloride In ethanol at 80℃; for 1.5h; Reflux; Stage #2: With sodium hydroxide In ethanol; water pH=14;

Latrepirdine dihydrochloride → dimebon (3613-73-8)

Conditions	Yield
With sodium hydroxide In 2-methyltetrahydrofuran; water for 1.25h;

2-methyl-5-vinylpyridine (140-76-1) → dimebon (3613-73-8)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: 9-bora-bicyclo[3.3.1]nonane / tetrahydrofuran / 0 °C / Reflux; Inert atmosphere 1.2: 1 h / Inert atmosphere 2.1: phosphorus tribromide / diethyl ether / 3 h / 0 °C / Inert atmosphere 3.1: N,N-dimethyl-formamide / 15 h / 60 °C / Inert atmosphere 4.1: sodium tetrahydroborate / methanol; water / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: potassium phosphate / ISOPROPYLAMIDE / 22 h / 100 °C 2: hydrogenchloride / isopropyl alcohol / 0.25 h View Scheme

2-(6-methylpyridin-3-yl) ethan-1-ol (100189-17-1) → dimebon (3613-73-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: phosphorus tribromide / diethyl ether / 3 h / 0 °C / Inert atmosphere 2: N,N-dimethyl-formamide / 15 h / 60 °C / Inert atmosphere 3: sodium tetrahydroborate / methanol; water / Inert atmosphere View Scheme

Br(1-)*C21H22N3(1+) → dimebon (3613-73-8)

Conditions	Yield
With sodium tetrahydroborate In methanol; water Inert atmosphere;	0.046 g

3-(2-azido-5-methylphenyl)pyridine (1296770-62-1) → dimebon (3613-73-8)

Conditions	Yield
Multi-step reaction with 5 steps 1: dichloromethane / 20 °C / Inert atmosphere 2: dirhodium(II) tetrakis(perfluorobutyrate) / toluene / 15 h / 90 °C / Inert atmosphere; Molecular sieve 3: potassium hydroxide / water / 2 h / 90 °C / Inert atmosphere 4: N,N-dimethyl-formamide / 15 h / 60 °C / Inert atmosphere 5: sodium tetrahydroborate / methanol; water / Inert atmosphere View Scheme
Multi-step reaction with 5 steps 1: dichloromethane / 20 °C / Inert atmosphere 2: ruthenium trichloride hydrate / Isopropyl acetate / 15 h / 80 °C / Inert atmosphere 3: potassium hydroxide / water / 2 h / 90 °C / Inert atmosphere 4: N,N-dimethyl-formamide / 15 h / 60 °C / Inert atmosphere 5: sodium tetrahydroborate / methanol; water / Inert atmosphere View Scheme

1-methyl-3-(2-azido-5-methylphenyl)pyridinium triflate (1296770-72-3) → dimebon (3613-73-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: dirhodium(II) tetrakis(perfluorobutyrate) / toluene / 15 h / 90 °C / Inert atmosphere; Molecular sieve 2: potassium hydroxide / water / 2 h / 90 °C / Inert atmosphere 3: N,N-dimethyl-formamide / 15 h / 60 °C / Inert atmosphere 4: sodium tetrahydroborate / methanol; water / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1: ruthenium trichloride hydrate / Isopropyl acetate / 15 h / 80 °C / Inert atmosphere 2: potassium hydroxide / water / 2 h / 90 °C / Inert atmosphere 3: N,N-dimethyl-formamide / 15 h / 60 °C / Inert atmosphere 4: sodium tetrahydroborate / methanol; water / Inert atmosphere View Scheme

CF3O3S(1-)*C13H13N2(1+) (1296770-97-2) → dimebon (3613-73-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium hydroxide / water / 2 h / 90 °C / Inert atmosphere 2: N,N-dimethyl-formamide / 15 h / 60 °C / Inert atmosphere 3: sodium tetrahydroborate / methanol; water / Inert atmosphere View Scheme

3-(2-amino-5-methylphenyl)pyridine (695185-44-5) → dimebon (3613-73-8)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: acetic acid; sodium nitrite / water / 1.5 h / 0 °C / Inert atmosphere 1.2: 0 - 20 °C / Inert atmosphere 2.1: dichloromethane / 20 °C / Inert atmosphere 3.1: dirhodium(II) tetrakis(perfluorobutyrate) / toluene / 15 h / 90 °C / Inert atmosphere; Molecular sieve 4.1: potassium hydroxide / water / 2 h / 90 °C / Inert atmosphere 5.1: N,N-dimethyl-formamide / 15 h / 60 °C / Inert atmosphere 6.1: sodium tetrahydroborate / methanol; water / Inert atmosphere View Scheme
Multi-step reaction with 6 steps 1.1: acetic acid; sodium nitrite / water / 1.5 h / 0 °C / Inert atmosphere 1.2: 0 - 20 °C / Inert atmosphere 2.1: dichloromethane / 20 °C / Inert atmosphere 3.1: ruthenium trichloride hydrate / Isopropyl acetate / 15 h / 80 °C / Inert atmosphere 4.1: potassium hydroxide / water / 2 h / 90 °C / Inert atmosphere 5.1: N,N-dimethyl-formamide / 15 h / 60 °C / Inert atmosphere 6.1: sodium tetrahydroborate / methanol; water / Inert atmosphere View Scheme

2-bromo-p-toluidine (583-68-6) → dimebon (3613-73-8)

Conditions	Yield
Multi-step reaction with 7 steps 1.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate / 1,4-dioxane; water / 2.5 h / 80 °C / Inert atmosphere 2.1: acetic acid; sodium nitrite / water / 1.5 h / 0 °C / Inert atmosphere 2.2: 0 - 20 °C / Inert atmosphere 3.1: dichloromethane / 20 °C / Inert atmosphere 4.1: dirhodium(II) tetrakis(perfluorobutyrate) / toluene / 15 h / 90 °C / Inert atmosphere; Molecular sieve 5.1: potassium hydroxide / water / 2 h / 90 °C / Inert atmosphere 6.1: N,N-dimethyl-formamide / 15 h / 60 °C / Inert atmosphere 7.1: sodium tetrahydroborate / methanol; water / Inert atmosphere View Scheme
Multi-step reaction with 7 steps 1.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate / 1,4-dioxane; water / 2.5 h / 80 °C / Inert atmosphere 2.1: acetic acid; sodium nitrite / water / 1.5 h / 0 °C / Inert atmosphere 2.2: 0 - 20 °C / Inert atmosphere 3.1: dichloromethane / 20 °C / Inert atmosphere 4.1: ruthenium trichloride hydrate / Isopropyl acetate / 15 h / 80 °C / Inert atmosphere 5.1: potassium hydroxide / water / 2 h / 90 °C / Inert atmosphere 6.1: N,N-dimethyl-formamide / 15 h / 60 °C / Inert atmosphere 7.1: sodium tetrahydroborate / methanol; water / Inert atmosphere View Scheme

3-pyridylboronic acid (1692-25-7) → dimebon (3613-73-8)

Conditions	Yield
Multi-step reaction with 7 steps 1.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate / 1,4-dioxane; water / 2.5 h / 80 °C / Inert atmosphere 2.1: acetic acid; sodium nitrite / water / 1.5 h / 0 °C / Inert atmosphere 2.2: 0 - 20 °C / Inert atmosphere 3.1: dichloromethane / 20 °C / Inert atmosphere 4.1: dirhodium(II) tetrakis(perfluorobutyrate) / toluene / 15 h / 90 °C / Inert atmosphere; Molecular sieve 5.1: potassium hydroxide / water / 2 h / 90 °C / Inert atmosphere 6.1: N,N-dimethyl-formamide / 15 h / 60 °C / Inert atmosphere 7.1: sodium tetrahydroborate / methanol; water / Inert atmosphere View Scheme
Multi-step reaction with 7 steps 1.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate / 1,4-dioxane; water / 2.5 h / 80 °C / Inert atmosphere 2.1: acetic acid; sodium nitrite / water / 1.5 h / 0 °C / Inert atmosphere 2.2: 0 - 20 °C / Inert atmosphere 3.1: dichloromethane / 20 °C / Inert atmosphere 4.1: ruthenium trichloride hydrate / Isopropyl acetate / 15 h / 80 °C / Inert atmosphere 5.1: potassium hydroxide / water / 2 h / 90 °C / Inert atmosphere 6.1: N,N-dimethyl-formamide / 15 h / 60 °C / Inert atmosphere 7.1: sodium tetrahydroborate / methanol; water / Inert atmosphere View Scheme

2-methyl-5-{2-[1-(4-methylphenyl)hydrazinyl]ethyl}pyridine (21241-08-7) → dimebon (3613-73-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: toluene / 24 h / 120 °C 2.1: hydrogenchloride; water / ethanol / 1.5 h / 80 °C 2.2: pH 14 View Scheme
Multi-step reaction with 2 steps 1.1: toluene / 24 h / 120 °C 2.1: hydrogenchloride / ethanol / 1.5 h / 80 °C / Reflux 2.2: pH 14 View Scheme

2-methyl-5-(2-[N-nitroso-(2-methylphenyl)amino]ethyl)pyridine → dimebon (3613-73-8)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium hydroxide / ethanol; water / 0.5 h / 60 °C / Inert atmosphere 1.2: 12 h / 60 °C / Inert atmosphere 2.1: toluene / 24 h / 120 °C 3.1: hydrogenchloride; water / ethanol / 1.5 h / 80 °C 3.2: pH 14 View Scheme

Methyl 6-methylnicotinate (5470-70-2) → dimebon (3613-73-8)

Conditions

Yield

Multi-step reaction with 9 steps 1.1: sodium hydride / N,N-dimethyl-formamide; toluene / 10 h / 80 °C 1.2: 2 h / 110 °C 1.3: pH 9 2.1: sulfur / 7 h / 110 °C 3.1: sodium hydroxide; water / ethanol / 17 h / 80 °C 3.2: pH 2 4.1: N-ethyl-N,N-diisopropylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 12 h / 20 °C 5.1: sodium tetrahydroborate; acetic acid / 1,4-dioxane / 3.5 h / 10 - 105 °C 6.1: hydrogenchloride / water / 30 °C 6.2: 1 h / 0 - 20 °C 6.3: 1 h 7.1: sodium hydroxide / ethanol; water / 0.5 h / 60 °C / Inert atmosphere 7.2: 12 h / 60 °C / Inert atmosphere 8.1: toluene / 24 h / 120 °C 9.1: hydrogenchloride / ethanol / 1.5 h / 80 °C / Reflux 9.2: pH 14 View Scheme

p-toluidine (106-49-0) → dimebon (3613-73-8)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: N-ethyl-N,N-diisopropylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 12 h / 20 °C 2.1: sodium tetrahydroborate; acetic acid / 1,4-dioxane / 3.5 h / 10 - 105 °C 3.1: hydrogenchloride / water / 30 °C 3.2: 1 h / 0 - 20 °C 3.3: 1 h 4.1: sodium hydroxide / ethanol; water / 0.5 h / 60 °C / Inert atmosphere 4.2: 12 h / 60 °C / Inert atmosphere 5.1: toluene / 24 h / 120 °C 6.1: hydrogenchloride / ethanol / 1.5 h / 80 °C / Reflux 6.2: pH 14 View Scheme

2-(6-methylpyridin-3-yl)acetic acid (19733-96-1) → dimebon (3613-73-8)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: N-ethyl-N,N-diisopropylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 12 h / 20 °C 2.1: sodium tetrahydroborate; acetic acid / 1,4-dioxane / 3.5 h / 10 - 105 °C 3.1: hydrogenchloride / water / 30 °C 3.2: 1 h / 0 - 20 °C 3.3: 1 h 4.1: sodium hydroxide / ethanol; water / 0.5 h / 60 °C / Inert atmosphere 4.2: 12 h / 60 °C / Inert atmosphere 5.1: toluene / 24 h / 120 °C 6.1: hydrogenchloride / ethanol / 1.5 h / 80 °C / Reflux 6.2: pH 14 View Scheme

1-(6-methyl-pyridin-3-yl)-ethanone (36357-38-7) → dimebon (3613-73-8)

Conditions

Yield

Multi-step reaction with 8 steps 1.1: sulfur / 7 h / 110 °C 2.1: sodium hydroxide; water / ethanol / 17 h / 80 °C 2.2: pH 2 3.1: N-ethyl-N,N-diisopropylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 12 h / 20 °C 4.1: sodium tetrahydroborate; acetic acid / 1,4-dioxane / 3.5 h / 10 - 105 °C 5.1: hydrogenchloride / water / 30 °C 5.2: 1 h / 0 - 20 °C 5.3: 1 h 6.1: sodium hydroxide / ethanol; water / 0.5 h / 60 °C / Inert atmosphere 6.2: 12 h / 60 °C / Inert atmosphere 7.1: toluene / 24 h / 120 °C 8.1: hydrogenchloride / ethanol / 1.5 h / 80 °C / Reflux 8.2: pH 14 View Scheme

N-(4-methylphenyl)-2-(6-methylpyridin-3-yl)acetamide (1229621-59-3) → dimebon (3613-73-8)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: sodium tetrahydroborate; acetic acid / 1,4-dioxane / 3.5 h / 10 - 105 °C 2.1: hydrogenchloride / water / 30 °C 2.2: 1 h / 0 - 20 °C 2.3: 1 h 3.1: sodium hydroxide / ethanol; water / 0.5 h / 60 °C / Inert atmosphere 3.2: 12 h / 60 °C / Inert atmosphere 4.1: toluene / 24 h / 120 °C 5.1: hydrogenchloride / ethanol / 1.5 h / 80 °C / Reflux 5.2: pH 14 View Scheme

4-methyl-N-(2-(6-methylpyridin-3-yl)ethyl)aniline (21241-10-1) → dimebon (3613-73-8)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: hydrogenchloride / water / 30 °C 1.2: 1 h / 0 - 20 °C 1.3: 1 h 2.1: sodium hydroxide / ethanol; water / 0.5 h / 60 °C / Inert atmosphere 2.2: 12 h / 60 °C / Inert atmosphere 3.1: toluene / 24 h / 120 °C 4.1: hydrogenchloride / ethanol / 1.5 h / 80 °C / Reflux 4.2: pH 14 View Scheme

4-methyl-N-[2-(6-methylpyridin-3-yl)ethyl]-N-nitrosoaniline (21241-09-8) → dimebon (3613-73-8)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium hydroxide / ethanol; water / 0.5 h / 60 °C / Inert atmosphere 1.2: 12 h / 60 °C / Inert atmosphere 2.1: toluene / 24 h / 120 °C 3.1: hydrogenchloride / ethanol / 1.5 h / 80 °C / Reflux 3.2: pH 14 View Scheme

4-[(6-methyl-pyridin-3-yl)-thioacetyl]-morpholine (19733-95-0) → dimebon (3613-73-8)

Conditions

Yield

Multi-step reaction with 7 steps 1.1: sodium hydroxide; water / ethanol / 17 h / 80 °C 1.2: pH 2 2.1: N-ethyl-N,N-diisopropylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 12 h / 20 °C 3.1: sodium tetrahydroborate; acetic acid / 1,4-dioxane / 3.5 h / 10 - 105 °C 4.1: hydrogenchloride / water / 30 °C 4.2: 1 h / 0 - 20 °C 4.3: 1 h 5.1: sodium hydroxide / ethanol; water / 0.5 h / 60 °C / Inert atmosphere 5.2: 12 h / 60 °C / Inert atmosphere 6.1: toluene / 24 h / 120 °C 7.1: hydrogenchloride / ethanol / 1.5 h / 80 °C / Reflux 7.2: pH 14 View Scheme

1-Methyl-4-piperidone (1445-73-4) → dimebon (3613-73-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: hydrogenchloride / water / 20 - 55 °C / Industry scale 1.2: 2.5 h / 5 - 45 °C / pH 12.4 / Industry scale 2.1: potassium hydroxide / diethylene glycol dimethyl ether / 42 h / 120 °C View Scheme

p-tolylhydrazine hydrochloride (637-60-5) → dimebon (3613-73-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: hydrogenchloride / water / 20 - 55 °C / Industry scale 1.2: 2.5 h / 5 - 45 °C / pH 12.4 / Industry scale 2.1: potassium hydroxide / diethylene glycol dimethyl ether / 42 h / 120 °C View Scheme

N-4-methylphenylhydrazine (539-44-6) → dimebon (3613-73-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium phosphate / ISOPROPYLAMIDE / 22 h / 100 °C 2: hydrogenchloride / isopropyl alcohol / 0.25 h View Scheme

5-bromo-2-methylpyridine (3430-13-5) → dimebon (3613-73-8)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: butyl magnesium bromide; methyllithium / tetrahydrofuran / 0.5 h / -10 - 0 °C 1.2: 1 h 1.3: 1 h / 40 °C 2.1: thionyl chloride; sodium hydroxide / Isopropyl acetate 2.2: 4 h / 50 °C 3.1: potassium hydroxide / diethylene glycol dimethyl ether / 42 h / 120 °C View Scheme
Multi-step reaction with 4 steps 1.1: butyl magnesium bromide; methyllithium / tetrahydrofuran / 0.5 h / -10 - 0 °C 1.2: 1 h 1.3: 1 h / 40 °C 2.1: thionyl chloride; sodium hydroxide / Isopropyl acetate 2.2: 4 h / 50 °C 3.1: potassium phosphate / ISOPROPYLAMIDE / 22 h / 100 °C 4.1: hydrogenchloride / isopropyl alcohol / 0.25 h View Scheme

1-(6-methylpyridin-3-yl)ethanol maleate → dimebon (3613-73-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: thionyl chloride; sodium hydroxide / Isopropyl acetate 1.2: 4 h / 50 °C 2.1: potassium hydroxide / diethylene glycol dimethyl ether / 42 h / 120 °C View Scheme
Multi-step reaction with 3 steps 1.1: thionyl chloride; sodium hydroxide / Isopropyl acetate 1.2: 4 h / 50 °C 2.1: potassium phosphate / ISOPROPYLAMIDE / 22 h / 100 °C 3.1: hydrogenchloride / isopropyl alcohol / 0.25 h View Scheme

glycyrrizhin (83896-44-0, 103000-77-7, 119479-05-9, 142394-43-2, 1405-86-3) + dimebon (3613-73-8) → C42H62O16*0.25C21H25N3

Conditions	Yield
In ethanol at 45 - 50℃;	93.9%

dimebon (3613-73-8) → Latrepirdine dihydrochloride

Conditions	Yield
With hydrogenchloride In acetone at 45 - 65℃; for 0.666667h; Inert atmosphere;	84%
With hydrogenchloride In methanol; water at 0℃; for 2h; pH=2 - 3;	83%
With hydrogenchloride In methanol at 0℃; for 2h; pH=2 - 3;	83%
With hydrogenchloride In methanol; water at 20℃; for 2h;	70%

iodomethyl diisopropylcarbamate (353736-55-7) + dimebon (3613-73-8) → 2-(((diisopropylcarbamoyl)oxy)methyl)-5-(2-(1-(((diisopropylcarbamoyl)oxy)methyl)-6-methylpyridin-1-ium-3-yl)ethyl)-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-2-ium diiodide

Conditions	Yield
In ethyl acetate at 20℃;	39%

iodomethyl diisopropylcarbamate (353736-55-7) + dimebon (3613-73-8) → 2-(((diisopropylcarbamoyl)oxy)methyl)-2,8-dimethyl-5-(2-(6-methylpyridin-3-yl)ethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-2-ium iodide (1402916-48-6)

Conditions	Yield
In ethyl acetate at 20℃;	15%

dimebon (3613-73-8) → 2,3,4,5-tetrahydro-2,8-dimethyl-5-(2-(6-methylpyridin-3-yl)ethyl)-1H-pyrido[4,3-b]indole N,N'-dioxide (1147893-49-9)

Conditions	Yield
With dihydrogen peroxide; acetic acid In water at 65 - 70℃; for 20h;

dimebon (3613-73-8) → C21H21N3O3 (1147893-75-1)

Conditions	Yield
With selenium(IV) oxide In pyridine at 80℃; for 48h;

dimebon (3613-73-8) → 2,8-dimethyl-5-(2-(6-methylpyridin-3-yl)ethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 2-oxide (1147893-84-2)

Conditions	Yield
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 25℃; for 24h;

dimebon (3613-73-8) → C21H31B2N3

Conditions	Yield
With borane-THF In tetrahydrofuran at 20℃;

dimebon (3613-73-8) → (4aRS,9bSR)-2,8-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole trihydrobromide

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium tetrahydroborate; trifluoroacetic acid / 3 h / 20 °C 1.2: pH 10 - 10.5 2.1: hydrogen bromide / ethanol; water / 0.5 h View Scheme

dimebon (3613-73-8) → (4aRS,9bSR)-2,8-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole

Conditions	Yield
Stage #1: dimebon With sodium tetrahydroborate; trifluoroacetic acid at 20℃; for 3h; Stage #2: With sodium hydroxide In water pH=10 - 10.5; stereoselective reaction;

dimebon (3613-73-8) → (4aRS,9bRS)-2,8-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole trihydrobromide

Conditions	Yield
Multi-step reaction with 3 steps 1.1: borane-THF / tetrahydrofuran / 20 °C 2.1: hydrogenchloride / 1,4-dioxane; water / 2 h / Reflux 2.2: pH 10 - 10.5 3.1: hydrogen bromide / ethanol; water / 0.5 h View Scheme

dimebon (3613-73-8) → (4aRS,9bRS)-2,8-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole

Conditions	Yield
Multi-step reaction with 2 steps 1.1: borane-THF / tetrahydrofuran / 20 °C 2.1: hydrogenchloride / 1,4-dioxane; water / 2 h / Reflux 2.2: pH 10 - 10.5 View Scheme

dimebon (3613-73-8) → 2,8-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole dihydrobromide

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium tetrahydroborate; trifluoroacetic acid / 3 h / 20 °C 1.2: pH 10 - 10.5 2.1: hydrogen bromide / ethanol; water / 0.5 h 3.1: oxygen / ethanol View Scheme

Upstream product

• 1227258-81-2 tert-butyl 8-methyl-5-(2-(6-methylpyridin-3-yl)ethyl)-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate 
• 1445-73-4 1-Methyl-4-piperidone 
• 21241-08-7 2-methyl-5-{2-[1-(4-methylphenyl)hydrazinyl]ethyl}pyridine 
• 3430-13-5 5-bromo-2-methylpyridine 
• 539-44-6 N-4-methylphenylhydrazine 
• 637-60-5 p-tolylhydrazine hydrochloride 
• 19733-95-0 4-[(6-methyl-pyridin-3-yl)-thioacetyl]-morpholine 
• 21241-09-8 4-methyl-N-[2-(6-methylpyridin-3-yl)ethyl]-N-nitrosoaniline 
• 21241-10-1 4-methyl-N-(2-(6-methylpyridin-3-yl)ethyl)aniline 
• 1229621-59-3 N-(4-methylphenyl)-2-(6-methylpyridin-3-yl)acetamide 
• 36357-38-7 1-(6-methyl-pyridin-3-yl)-ethanone 
• 19733-96-1 2-(6-methylpyridin-3-yl)acetic acid 
• 106-49-0 p-toluidine 
• 5470-70-2 Methyl 6-methylnicotinate 

Relevant articles and documents

SUSTAINED RELEASE COMPOSITION CONTAINING TETRAHYDROPYRIDO Y4, 3-b¨INDOLE DERIVATIVE AND PREPARATION METHOD OF DERIVATIVE

The present invention relates to a sustained-release composition containing 2,3,4,5-tetrahydro-2,8-dimethyl-5-[2-(6-methyl-3-pyridyl)ethyl]-1H-pyrido[4,3-b]indole or a pharmaceutically acceptable salt thereof as an active ingredient, preparation thereof and the compound. The composition is suitable for oral administration by one time per day, and achieves the peak plasma concentration at 1.0 to 3 hours after oral administration. The composition is suitable for manufacturing a medicament for treatment of cognitive dysfunction syndrome, Alzheimer's disease, Parkinson's disease, Huntington's disease, or senile dementia.

Sustained-release composition containing tetrahydropyrido[4,3-b]indole derivatives and preparation of the derivatives

The present invention relates to a sustained-release composition containing 2,3,4,5-tetrahydro-2,8-dimethyl-5-[2-(6-methyl-3-pyridyl)ethyl]-1H-pyrido[4,3-b]indole or a pharmaceutically acceptable salt thereof as an active ingredient, preparation thereof and the compound. The composition is suitable for oral administration by one time per day, and achieves the peak plasma concentration at 1.0 to 3 hours after oral administration. The composition is suitable for manufacturing a medicament for treatment of cognitive dysfunction syndrome, Alzheimer's disease, Parkinson's disease, Huntington's disease, or senile dementia.

Ruthenium-catalyzed γ-carbolinium ion formation from aryl azides; Synthesis of dimebolin

A range of γ-carbolines were produced stereoselectively from ruthenium(III)-catalyzed reactions of 3-pyridyl substituted aryl azides. Other catalysts and conditions were neither as selective nor as high-yielding. This method was used to synthesize dimebolin in a concise and efficient manner.

NOVEL FORMS OF (2,8-DIMETHYL-5-[2-(6-METHYLPYRIDIN-3-YL)ETHYL]-3,4-DIHYDRO-1H-PYRIDO[4,3-B] INDOLE)

The present invention relates to novel solid forms of latrepirdine, also known as Dimebon) designated Form A, Form B, and a noncrystalline form, and relates to methods for the preparation of each form. The present invention also relates to a novel MVP oxalate salt and hydrate thereof, and its preparation and use in the preparation of latrepirdine.

SYNTHESIS OF 9-(ARYLALKYL)-1,2,3,4-TETRAHYDRO-Υ-CARBOLINE AND ANALOGUES AND INTERMEDIATES

The present invention pertains generally to methods of preparing certain 9-(arylalkyl)- 1,2,3,4-tetrahydro-Υ-carboline compounds and their analogues, and especially to methods of preparing dimebon. The present invention also pertains to methods of preparing certain intermediate compounds which find use in the synthesis of the 9-(arylalkyl)-1,2,3,4-tetrahydro-γ-carboline compounds.

PYRIDOINDOLE MODULATORS OF NMDA RECEPTOR AND ACETYLCHOLINESTERASE

The present invention relates to new pyridoindole modulators of NMDA receptors, AMPA receptors, and/or L-type calcium channels, and/or inhibitors of acetylcholinesterase, pharmaceutical compositions thereof, and methods of use thereof.

SUBSTITUTED 2,3,4,5-TETRAHYDRO-1H-PYRIDO[4,3-B]INDOLES, METHODS FOR THE PRODUCTION AND USE THEREOF

The invention relates to antagonists of serotonin 5-HT6 receptors simultaneously regulating homeostasis of Ca+2 ions in cells, representing substituted 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles of the general formula 1, pharmaceutically acceptable salts and/or hydrate thereof. In the general formula 1: R1 represents amino group substituent selected from optionally substituted C1-C5 alkyl; R2i is one or more substituents selected from hydrogen, halogen, C1-C3 alkyl, CF3, OCF3; Ar is phenyl optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, substituted amino group, or CF3; or optionally substituted aromatic 6-membered heterocycle comprising 1-2 nitrogen atoms in the cycle; W represents ethylene group -CH2-CH2-, ethenyl group -CH=CH-, or ethynyl group -C≡C-. The invention also relates to the novel compounds selected from the compounds of the general formula 1, methods for their preparation, pharmaceutical compositions and methods of their use.

METHODS AND COMBINATION THERAPIES FOR TREATING ALZHEIMER'S DISEASE

The invention provides methods and combination therapies for treating and/or preventing and/or slowing the onset and/or development of Alzheimer's disease using a hydrogenated pyrido (4,3-b) indole (e.g., dimebon) in conjunction with another compound, pharmaceutically acceptable salt thereof or therapy for Alzheimer's disease.

LIGANDS OF ALPHA-ADRENOCEPTORS AND OF DOPAMINE, HISTAMINE, IMIDAZOLINE AND SEROTONIN RECEPTORS AND THE USE THEREOF

The invention relates to novel ligands the broad spectrum of biological activity of which includes simultaneously α-adrenoceptors, dopamine receptors, histamine receptors, imidazoline receptors and serotonin receptors, among them serotonin 5-HT7 receptors, which are compounds of general formula 1 in the form of free bases, geometrical isomers, racemic mixtures or individual optical isomers, pharmaceutically acceptable salts and/or hydrates, wherein: R1 is a substituent of amino group, selected from hydrogen, optionally substituted C1-C4 alkyl, acyl, heterocyclyl, alkoxycarbonyl, substituted sulfonyl; R2 is a substituent of cyclic system, selected from hydrogen, halogen, optionally substituted C1-C4 alkyl, CF3, CN, alkoxy, alkoxycarbonyl, carboxyl, heterocyclyl or substituted sulfonyl; Ar is optionally substituted aryl not necessarily annalated with heterocyclyl, or optionally substituted aromatic heterocyclyl; W is optionally substituted (CH2)m group, optionally substituted CH=CH group, optionally substituted CH2-CH=CH group, C≡C group, SO2 group; n = 1, 2; m = 1, 2, 3; solid line accompanied by dotted line, i.e. (---) may represent single or double bond. The invention also relates to active ingredients, pharmaceutical compositions comprising the said ligands as active ingredients; to novel medicaments useful for treatment of diseases and conditions of central nervous system (CNS) of humans and warm-blooded animals.

[11C]Dimebon, radiosynthesis and lipophilicity of a new potential PET agent for imaging of Alzheimer's disease and Huntington's disease

[11C]Dimebon (2-[11C]methyl-8-methyl-5-(2-(6-methylpyridin-3-yl)ethyl)-2,3 ,4,5-tetrahydro-1H-pyrido[4,3-b]indole), a new potential PET agent for imaging of Alzheimer's disease and Huntington's disease, was prepared by N-[11C]methylation of desmethyl-Domebon precursor with [11C]CH3OTf and purified with a semi-preparative HPLC method in 30-40% decay corrected radiochemical yield and 222-296 GBq/μmol specific activity at EOB. The measured lipophilicity coefficient (Log P) value of [11C]Dimebon was 2.53.