ALOSETRON CAS 122852-42-0

Introduction：Basic information about ALOSETRON CAS 122852-42-0, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

ALOSETRON Basic information

• Product Name: ALOSETRON
• Synonyms: ALOSETRON;ALOSETRON2,3,4,5-Tetrahydro-5-methyl-2-((5-methyl-1H-imidazol-4-yl)methyl)-1H-pyrido(4,3-b)indol-1-one;5-Methyl-2-[(4-methyl-1H-imidazol-5-yl)methyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-1-one;5-METHYL-2-[(5-METHYL-1H-IMIDAZOL-4-YL)METHYL]-3,4-DIHYDROPYRIDO[4,3-B]INDOL-1-ONE;GR-68755X;GR-68755;Alosetron(GR-68755X;GR 68755; GR 68755X; LOTRONEX;GR-68755;GR68755;1H-Pyrido[4,3-b]indol-1-one, 2,3,4,5-tetrahydro-5-methyl-2-[(4-methyl-1H-imidazol-5-yl)methyl]-
• CAS: 122852-42-0
• MF: C17H18N4O
• MW: 294.35
• Mol File: 122852-42-0.mol

ALOSETRON Chemical Properties

• Melting point: 238-240 °C
• Boiling point: 648.1±55.0 °C(Predicted)
• density: 1.34±0.1 g/cm3(Predicted)
• storage temp.: Store at -20°C
• solubility: DMSO
• form: Powder
• pka: 14.10±0.10(Predicted)

Safety Information

• Hazard Codes: Xi
• Risk Statements: 36/37/38
• Safety Statements: 26-36

ALOSETRON Usage And Synthesis

Chemical Properties

crystalline powder

Originator

Alosetronhydrochloride,GlaxoSmithKline

Uses

Anti-emetic.

Indications

Alosetron (Lotronex) is a 5-HT3 receptor antagonist.Blocking this receptor results in decreased GI motility.Alosetron received FDA approval in February 2000 forthe treatment of women with diarrhea-predominantIBS. In November 2000, at the request of the FDA, thedrug was voluntarily withdrawn due to reported casesof ischemic colitis, including some fatalities.

Definition

ChEBI: A pyrido[4,3-b]indole compound having a 5-methyl-1H-imidazol-4-ylmethyl group at the 2-position.

Manufacturing Process

4-(Chloromethyl)-1-(triphenylmethyl)-1H-imidazole.
Thionyl chloride (0.829 g) was added over 1 min to a stirred suspension of 1-(triphenylmethyl)-1H-imidazole-4-methanol (1.3 g) in a mixture ofdichloromethane (50 ml) and DMF (1.0 ml) at 23°C. The solution so obtainedwas stirred for 15 min. and extracted with 8% sodium bicarbonate solution(80 ml). The organic phase was washed with water (50 ml), dried andevaporated to give an oil which solidified. The solid was slurried in hexane andfiltered to give the title compound (1.28 g), m.p. 139-141°C.
3,4-Dihydro-4-methylcyclopent[b]indol-1(2H)-one oxime.
3,4-Dihydro-4-methylcyclopent[b]indol-1(2H)-one (1.7 g) and hydroxylaminehydrochloride (1.925 g) in pyridine were heated at 60°C for 18 h and cooled.The reaction mixture was evaporated in vacuo to a residue to which wasadded 8% sodium bicarbonate (150 ml). Extraction with ethyl acetate (300ml) produced a suspension in the organic layer; this layer and associated solidwas separated from the aqueous layer. The aqueous layer was re-extractedwith ethyl acetate (250 ml). The combined organic extracts (and suspendedsolid) were evaporated to a residue, boiled with a mixture of ethanol (150 ml)and methanol (150 ml) and cooled to 50°C. The residue was adsorbed fromthis solution on to FCC silica and applied to an FCC column. Elution with ethylacetate/3-10% methanol provided the title compound (1.69 g), m.p. 219-224°C (decomp.).
2,3,4,5-Tetrahydro-5-methyl-1H-pyrido[4,3-b]indol-1-one.
3,4-Dihydro-4-methylcyclopent[b]indol-1(2H)-one oxime (1.53 g),polyphosphoric acid (409 g) and dioxan (15 ml) were heated at 110-120°C for2.2 h under nitrogen. The reaction mixture was cooled, and treated with 2 Nsodium carbonate solution (1 L). The suspension was extracted with ethylacetate (4x400 ml) and the combined extracts were dried. Evaporation gave asolid (1.43 g) which was recrystallised from ethyl acetate/cyclohexane. Thissolid was purified by FCC, eluting with dichloromethane:ethanol:ammoniasolution (200:10:1) to give a solid (1.26 g) which was recrystallised fromethanol to provide the title compound (960 mg), m.p. 234-238°C.
2,3,4,5-Tetrahydro-5-methyl-2-[(5-methyl-1H-imidazol-4-yl)methyl]-1Hpyrido[4,3-b]indol-1-one maleate.
A mixture of 2,3,4,5-tetrahydro-5-methyl-1H-pyrido[4,3-b]indol-1-one (0.6 g)and 78% sodium hydride dispersion in mineral oil (0.109 g) in dry DMF (15ml) was stirred under nitrogen at 50°C until hydrogen evolution ceased (ca.1.5 h). The mixture was cooled to 40°C and a solution of 4-(chloromethyl)-5-methyl-1-(triphenylmethyl)-1H-imidazole (1.12 g) in dry THF (15 ml) wasadded. The reaction was then stirred at 40°C for 3 h, at 20°C for 16 h and afurther portion of 4-(chloromethyl)-5-methyl-1-(triphenylmethyl)-1H-imidazole(1.12 g) in dry THF (15 ml) was added. The resulting mixture was heated at40°C for 3 h, quenched with water (20 ml) and acetic acid (20 ml), andheated at 100°C for 2 h. The mixture was then concentrated in vacuo to ca.60 ml, diluted with 1 M hydrochloric acid (40 ml) and washed with ethylacetate (3x50 ml). The organic phase was discarded and the acidic aqueousphase was basified (pH=9) with potassium carbonate and extracted with ethylacetate:ethanol (20:1; 3x100 ml). The extracts were combined, dried andevaporated to give a brown gum (ca. 1 g). This gum was adsorbed onto silicaand purified by FCC eluting with dichloromethane:ethanol:ammonia solition(100:8:1) to give a pale brown solid (0.8 g); m.p. 238-240°C (decomp.). Thissolid was dissolved in a mixture of (hot ethanol and methanol (1:1; 100 ml)and treated with an ethanolic solution of maleic acid (3.18 g). The resultingsolution was concentrated to ca. 20 ml and diluted with dry diethyl ether (ca.8 ml) to precipitate the title compound (0.75 g) as an off-white solid meltingpoint 160-162°C. Hydrochloride may be prepared by treating the above solidwith an equivalent of an ethanolic solution of HCl.

Brand name

Lotronex (GlaxoSmithKline).

Therapeutic Function

Antidiarrheal

ALOSETRON Preparation Products And Raw materials

• Raw materials: 1-TRITYL-1H-IMIDAZOLE-4-METHANOL-->Sodium hydride-->Polyphosphoric acid-->Thionyl chloride-->Maleic acid-->Hydroxylamine hydrochloride-->2-Methoxyethanol