Apraclonidine hydrochloride CAS 73218-79-8

Introduction：Basic information about Apraclonidine hydrochloride CAS 73218-79-8, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Apraclonidine hydrochloride Basic information

• Product Name: Apraclonidine hydrochloride
• Synonyms: 2-(4-amino-2,6-dichlorophenylimino)imidazolidinehydrochloride;2,6-dichloro-n(sup1)-(2-imidazolidinylidene)-1,4-benzenediaminehydrochlorid;2,6-dichloro-n(sup1)-(4,5-dihydro-1h-imidazol-2-yl)-1,4-benzenediaminemonoh;2-[4-AMINO-2,6-DICHLOROANILINO]-2-IMIDAZOLINE HYDROCHLORIDE;2-[(4-AMINO-2,6-DICHLOROPHENYL)IMINO]IMIDAZOLIDINE MONOHYDROCHLORIDE;P-AMINOCLONIDINE HYDROCHLORIDE;2,6-Dichloro-N1-(4,5-dihydro-1H-imidazol-2-yl)-1,4-benzenediamine Hydrochloride;AL 02145
• CAS: 73218-79-8
• MF: C9H11Cl3N4
• MW: 281.57
• Product Categories: Heterocyclic Compounds;Bases & Related Reagents;Heterocycles;Intermediates & Fine Chemicals;Nucleotides;Pharmaceuticals
• Mol File: 73218-79-8.mol

Apraclonidine hydrochloride Chemical Properties

• Melting point: >2300C
• storage temp.: Keep in dark place,Inert atmosphere,Room temperature
• solubility: 45% (w/v) aq 2-hydroxypropyl-β-cyclodextrin: 1.4 mg/mL Solutions may be stored for several days at 4°C
• form: solid
• color: white
• Stability: Moisture Sensitive
• Major Application: pharmaceutical (small molecule)
• InChI: 1S/C9H10Cl2N4.ClH/c10-6-3-5(12)4-7(11)8(6)15-9-13-1-2-14-9;/h3-4H,1-2,12H2,(H2,13,14,15);1H
• InChIKey: OTQYGBJVDRBCHC-UHFFFAOYSA-N
• SMILES: Clc1c(c(cc(c1)N)Cl)N=C2NCCN2.Cl
• CAS DataBase Reference: 73218-79-8(CAS DataBase Reference)

Safety Information

• Hazard Codes: T
• Risk Statements: 23/24/25
• Safety Statements: 22-36/37/39-45
• RIDADR: UN 2811 6.1/PG 1
• WGK Germany: 3
• HazardClass: 6.1(b)
• PackingGroup: III
• HS Code: 2933290000
• Storage Class: 6.1A - Combustible acute toxic Cat. 1 and 2 very toxic hazardous materials
• Hazard Classifications: Acute Tox. 1 Oral STOT SE 1

Apraclonidine hydrochloride Usage And Synthesis

Chemical Properties

Crystalline Solid

Originator

Alfadrops,Cipla Limited,India

Uses

Apraclonidine hydrochloride can be used as α-Adrenergic agonist; structural analog of clonidine and be used for treatment of post-surgical elevated intraocular pressure.

Uses

a-Adrenergic agonist; structural analog of clonidine. Used for treatment of post-surgical elevated intraocular pressure

Definition

ChEBI: The hydrochloride salt of apraclonidine.

Manufacturing Process

The preparation of p-aminoclonidine (apraclonidine) consists of 6 steps.
In the first step 2,6-dichloro-4-nitroaniline was converted to 2,6-dicloro-4-nitrophenylisothiocyanate by addition of thiophosgene in toluene according tothe method described in Great Britain Patent No.: 1,131,780 (Beck et al.).
The second step involved the conversation of 2,6-dichloro-4-nitrophenylisothiocyanateto 1-(2-aminoethyl)-3-(2,6-dichloro-4-nitrophenyl)-thioureaethylenediamine solvate. The solution of 2,6-dicloro-4-nitrophenylisothiocyanate(432 g, 1.73 mol) in 2 L of toluene was added dropwise to thecooled (0°C) solution ethylenediamine (244 ml, 3.66 mol, 2.1 eq.) in toluene(4 L) under a nitrogen atmosphere. 2-Propanol (1 L) was added and after 5minutes, the solid was collected by filtration, washed with 20% 2-propanol/toluene, and dried to a constant weight of 602 g (94%). Thisproduct is hygroscopic, mp 120°C (dec.).
The third step was the conversation of 1-(2-aminoethyl)-3-(2,6-dichloro-4-nitrophenyl)-thiourea ethylenediamine solvate to 2-[(2,6-dicloro-4-nitrophenyl)imino]imidazoline ethylenediamine solvate. (500 g, 1.35 mol) ofabove prepared thiourea solvate was suspended with toluene (4 L) and washeated at reflux for 15 hours. The mixture was cooled to 23°C and 1 Maqueous hydrochloric acid (4 L) was added. After stirring for 10 min thebiphasic mixture was filtered to remove a sticky insoluble material. Theaqueous phase was neutralized to pH=7.0 using 50% NaOH. After stirring for1 hour the yellow solid was collected by filtration, washed with water (4 L)and t-butyl methyl ether (2 L) and dried in air to constant weight of 195 g(52%), m.p. 289-292°C.
The fourth step was the conversation of 2-[2,6-dichloro-4-nitrophenyl)imino]imidazoline (150 g, 0.55 mol) in methanol (1,5 L) to 2-[(2,6-dichloro-4-aminophenyl)imino]imidazoline by hydrogen with 30 g Raney nickel catalyst at23°C for 22 hours. After removing the catalyst hydrogen chloride gas wasbubbled into solution until pH of the reaction mixture was 1.0. The solventwas rotary removed in vacuum and the residual solid was slurried with 2-propanol (1 L). The solvent was again removed by rotary evaporation, thecream solid was triturated with 2-propanol (600 ml). After aging for 1 hour,the solid was collected by filtration, washed with 2-propanol and t-butylmethyl ether, and dried for 15 hours at 6°C and t-butyl methyl ether, anddried for 15 hours at 60°C and 20 mm Hg. Yield of dihydrochloride 167 g (96%), mp 260°C (dec.).
The dihydrochloride was converted to the monochloride (step 5) by adding 5M aqueous sodium hydroxide dropwise to pH=6.5 at 5°C for 2 hours. Yield ofhydrochloride 87%.
The last step was recrystallization of product from water. The recrystallizedmaterial had m.p. 300°C. Calculated for: C9H10Cl2N4HCl: C, 38.39; H, 3.94;N, 19.90; Cl, 37.78. Found: C, 38.36; H, 3.91; N, 19.83; Cl, 37.77.

Brand name

Iopidine(Alcon).

Therapeutic Function

Antiglaucoma

References

[1] Patent: CN104557716, 2017, B. Location in patent: Paragraph 0042; 0043; 0044; 0045; 0046; 0047; 0048-0057

Apraclonidine hydrochloride Preparation Products And Raw materials

• Raw materials: Isopropyl alcohol-->Methanol-->Thiophosgene-->Toluene-->tert-Butyl methyl ether-->Ethylenediamine-->Hexane-->Aluminium-nickel-->Apraclonidine-->Hydrochloric acid