58108-05-7

Basic information

• Product Name: 3-Amino-3-azabicyclo[3.3.0]octane hydrochloride
• Synonyms: Gliclazide Intermediate 2;3-AMino-3-azabicyclo[3.3.0]octanehydrochloride(gliclazideinterMediate);3-aMino-3-Azabicyclooctane HCl;octahydrocyclopenta[c]pyrrol-2-aMine hydrochloride;3-AMino-3-azabicyclo[3.3.0]octane hydrochlorid;Hexahydrocyclopenta[c]pyrrol-2(1H)-aMine hydrochloride;Cyclopenta[c]pyrrol-2(1H)-aMine,hexahydro-, hydrochloride (1:1);N-Amino-azabicyclo-[3,3,0]-octane
• CAS NO: 58108-05-7
• Molecular Formula: C₇H₁₄N₂*ClH
• Molecular Weight: 162.66
• EINECS: 261-131-9
• Product Categories: NULL;Pyrrolidines;Building Blocks;Heterocyclic Building Blocks
• Mol File: 58108-05-7.mol
• Article Data: 4

Chemical Properties

• Melting Point: 170-174 °C(lit.)
• Boiling Point: 229.9 °C at 760 mmHg
• Flash Point: 92.9 °C
• Appearance: /
• Storage Temp.: Inert atmosphere,Room Temperature
• Solubility: Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly),Water (Slightly)
• Stability: Hygroscopic
• CAS DataBase Reference: 3-Amino-3-azabicyclo[3.3.0]octane hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: 3-Amino-3-azabicyclo[3.3.0]octane hydrochloride(58108-05-7)
• EPA Substance Registry System: 3-Amino-3-azabicyclo[3.3.0]octane hydrochloride(58108-05-7)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• Hazardous Substances Data: 58108-05-7(Hazardous Substances Data)

Usage

Uses

3-Amino-3-azabicyclo[3,3,0]octane Hydrochloride is used as a reactant in the synthesis of cannabinoid receptor antagonists.

General Description

3-Amino-3-azabicyclo[3.3.0]octane hydrochloride is also referred to as N-amino-3-azabicyclo[3.3.0]octane monohydrochloride.

InChI:InChI=1/C7H14N2.ClH/c8-9-4-6-2-1-3-7(6)5-9;/h6-7H,1-5,8H2;1H

Synthetic route

N-amino-aza-3-bicyclo<3.3.0>octane (54528-00-6) → 3-azabicyclo<3.3.0>oct-3-yl-amine monohydrochloride (58108-05-7)

Conditions	Yield
With hydrogenchloride	96%

N-amino-1,2-cyclopentanedicarboximide → 3-azabicyclo<3.3.0>oct-3-yl-amine monohydrochloride (58108-05-7)

Conditions	Yield
Stage #1: N-amino-1,2-cyclopentanedicarboximide With aluminum (III) chloride In tetrahydrofuran at 45℃; for 0.333333h; Large scale; Stage #2: With sodium tetrahydroborate In tetrahydrofuran for 6h; Reflux; Large scale; Stage #3: With hydrogenchloride In tetrahydrofuran pH=3; Solvent; Temperature; Large scale;	81.3%
Multi-step reaction with 2 steps 1: acetic acid; pyrographite; ruthenium(III) chloride trihydrate; hydrogen / water / 16 h / 140 °C / 60006 Torr / Autoclave 2: hydrogenchloride View Scheme

gliclazide (21187-98-4) → toluene-4-sulfonamide (70-55-3) + 3-azabicyclo<3.3.0>oct-3-yl-amine monohydrochloride (58108-05-7)

Conditions	Yield
With chloride ions In various solvent(s) at 37℃; for 24h; Product distribution; various concentrations of anions and cations, with and without human serum proteins;

cis-cyclopentane-1,2-dimethanol → 3-azabicyclo<3.3.0>oct-3-yl-amine monohydrochloride (58108-05-7)

Conditions	Yield
With hydrogenchloride; hydrazine hydrochloride In water at 140℃; under 1672.11 - 4256.29 Torr; for 5h; Autoclave;

cis-cyclopentane-1,2-dimesylate → 3-azabicyclo<3.3.0>oct-3-yl-amine monohydrochloride (58108-05-7)

Conditions	Yield
With hydrogenchloride; hydrazine hydrochloride In water for 4h; Reflux;

cis-1,2-dichloromethylcyclopentane → 3-azabicyclo<3.3.0>oct-3-yl-amine monohydrochloride (58108-05-7)

Conditions	Yield
With hydrogenchloride; hydrazine hydrochloride In water for 10h; Reflux;

cis-1-hydroxymethyl-2-chloromethylcyclopentane → 3-azabicyclo<3.3.0>oct-3-yl-amine monohydrochloride (58108-05-7)

Conditions	Yield
With hydrogenchloride; hydrazine hydrochloride In water at 115 - 120℃; under 1140.08 - 1900.13 Torr; Autoclave;

3-azabicyclo<3.3.0>oct-3-yl-amine monohydrochloride (58108-05-7) + 4-toluenesulfonylurea (1694-06-0) → gliclazide (21187-98-4)

Conditions	Yield
In toluene for 3h; Reflux;	86%

1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-5-methyl-1H-imidazole-4-carboxylic acid (796875-26-8) + 3-azabicyclo<3.3.0>oct-3-yl-amine monohydrochloride (58108-05-7) → 1-(4-chloro-phenyl)-2-(2,4-dichloro-phenyl)-5-methyl-1H-imidazole-4-carboxylic acid (hexahydro-cyclopenta[c]pyrrol-2-yl)-amide

Conditions	Yield
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 16h;	84%

benzaldehyde (100-52-7) + 3-azabicyclo<3.3.0>oct-3-yl-amine monohydrochloride (58108-05-7) → (E)-N-(3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl)-1-phenylmethanimine

Conditions	Yield
With magnesium sulfate; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;	71%

3-azabicyclo<3.3.0>oct-3-yl-amine monohydrochloride (58108-05-7) + phenylpropyolic acid (637-44-5) → N-(hexahydrocyclopenta[c]pyrrol-2(1H)-yl)-3-phenylpropiolamide

Conditions	Yield
With triethylamine In tetrahydrofuran at 20℃; for 2h;	50%

5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (863034-64-4, 1029820-46-9) + 3-azabicyclo<3.3.0>oct-3-yl-amine monohydrochloride (58108-05-7) → 5-(4-chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (hexahydro-cyclopenta[c]pyrrol-2-yl)-amide

Conditions	Yield
With 1-hydroxybenzotriazol-hydrate; triethylamine In dichloromethane at 28 - 29℃; for 0.5h;	34%

formaldehyd (50-00-0) + 3-azabicyclo<3.3.0>oct-3-yl-amine monohydrochloride (58108-05-7) → (3aR,6aS)-cis-N-methylenehexahydrocyclopenta[c]pyrrol-2(1H)-amine (1190890-65-3)

Conditions	Yield
With sodium acetate In water

3-azabicyclo<3.3.0>oct-3-yl-amine monohydrochloride (58108-05-7) → rac-4-[(3S,3aS,6aR)-2-[(E)-benzylideneamino]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-3-yl]benzonitrile

Conditions	Yield
Multi-step reaction with 2 steps 1: magnesium sulfate; N-ethyl-N,N-diisopropylamine / dichloromethane / 20 °C 2: tris[2-phenylpyridinato-C2,N]iridium(III); lithium acetate / dimethyl sulfoxide / 0.17 h / 40 °C / Inert atmosphere; Irradiation View Scheme

3-azabicyclo<3.3.0>oct-3-yl-amine monohydrochloride (58108-05-7) + phenyl chloroformate (1885-14-9) → phenyl hexahydrocyclopenta[c]pyrrol-2(1H)-ylcarbamate (700359-75-7)

Conditions	Yield
With TEA In dichloromethane at 0 - 20℃; for 3h;

3-azabicyclo<3.3.0>oct-3-yl-amine monohydrochloride (58108-05-7) → 3-phenyl-5a,6,7,8,8a,9-hexahydro-1H,5H-cyclopenta[d]pyrazolo[1,2-a]pyridazin-1-one

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylamine / tetrahydrofuran / 2 h / 20 °C 2: copper(ll) bromide; Bathocuproine / chlorobenzene / 0.5 h / Reflux View Scheme

Upstream product

• 54528-00-6 N-amino-aza-3-bicyclo<3.3.0>octane 
• 1050666-51-7 N-amino-1,2-cyclopentanedicarboximide 
• 21187-98-4 gliclazide 

Downstream Products

• 21187-98-4 gliclazide 
• 700359-75-7 phenyl hexahydrocyclopenta[c]pyrrol-2(1H)-ylcarbamate 

Relevant articles and documents

Synthesis process of N-amino-3-azabicyclo [3, 3, 0] octane hydrochloride

The invention provides a synthesis process of N-amino-3-azabicyclo [3, 3, 0] octane hydrochloride, and relates to the technical field of gliclazide intermediate synthesis. The synthesis process comprises the following steps: heating, dehydrating and cyclizing 2-carbamoyl amine cyclopentanecarboxylate serving as a raw material under the catalysis of an acid catalyst until no water is generated, adding toluene, refluxing and dissolving, and carrying out post-treatment to obtain 1, 2-cyclopentane dicarboximide; reacting the 1, 2-cyclopentane dicarboximide with chloramine under an alkaline condition, and carrying out post-treatment to obtain N-amino-1, 2-cyclopentane dicarboximide; and reducing the amino-1, 2-cyclopentane dicarboximide in the presence of sodium borohydride/aluminum trichloride and an organic solvent, and performing post-treatment to obtain the product. According to the present invention, the three-step synthesis is performed through the catalytic cyclization reaction, the nucleophilic substitution reaction and the reduction reaction, the raw materials are cheap and easily available, the high toxicity product is not generated, the harsh reaction condition is not required, the yield and the purity of each step are high, and the method is suitable for the large-scale industrial production.

Preparation method of gliclazide side chain and preparation method of gliclazide

The invention relates to a preparation method of N-amino-3-azabicyalo [3.3.0] octane serving as a gliclazide side chain. The gliclazide side chain is obtained by carrying out one-step hydrogenation reduction on N-cyclopentyl amine imide through a transition metal atom-modified ruthenium-carbon catalyst. The activity of the modified ruthenium-carbon catalyst used in the method is obviously higher than that of an existing commercial ruthenium-carbon catalyst, so that the imide hydrogenation reaction which is hard to realize in the N-cyclopentyl amine imide can be carried out successfully. The preparation method of the gliclazide side chain is safe, efficient, high in yield and simple for posttreatment; the catalyst can be cyclically used indiscriminately, so that the production cost is substantially reduced, and green synthesis is basically realized; no waste water and no waste slag are produced; and the preparation method is particularly suitable for large-scale industrial production. The invention further relates to a production method of gliclazide, which has the advantages of short synthesis path, high yield, low preparation cost and the like.