73232-52-7

Usage

Originator

University of Chicago (United States)

Biochem/physiol Actions

Methylnaltrexone bromide is a narcotic antagonist. It is a peripheral mu-opiod receptor antagonist that cannot cross the blood-brain barrier. It reverses many opioid side-effects without interfering with pain relief.

Synthesis

The synthesis of methylnaltrexone bromide proceeds in a straightforward manner via the alkylation of naltrexone 90 in the following scheme. Naltrexone 90 was reacted with methyl bromide in 1-methyl-2-pyrrolidinone at 60 °C. The resulting crude product was treated with sodium methoxide in methanol/ water at 55 °C to remove any undesired phenolic (Oalkylated) side-products. The resulting crude sodium salt was treated with hydrobromic acid in methanol/water and upon crystallization gave methylnaltrexone bromide (XII) in 35% overall yield.

InChI:InChI=1/C21H25NO4.BrH/c1-22(11-12-2-3-12)9-8-20-17-13-4-5-14(23)18(17)26-19(20)15(24)6-7-21(20,25)16(22)10-13;/h4-5,12,16,19,25H,2-3,6-11H2,1H3;1H/t16-,19+,20+,21-,22?;/m1./s1

Upstream product

• 1013911-70-0 N-methylnaltrexone zwitterion 
• 74-83-9 methyl bromide 
• 16590-41-3 Naltrexone 
• 111129-14-7 3-O-acetylnaltrexone 
• 16676-29-2 naltrexone Hydrochloride 
• 111555-53-4 naltrindole 
• 1048360-09-3 3-O-(isobutyryl)-17-(cyclopropylmethyl)-4,5a-epoxy-14-hydroxy-6-N-methylmorphinan iodide 
• 73232-53-8 N-Methylnaltrexone iodide 
• 1082510-80-2 CH₃O₄S^(1-)*C₂₄H₃₀NO₆⁽¹⁺⁾ 

Downstream Products

• 1005410-32-1 Br^(1-)*C₂₁H₂₆NO₄⁽¹⁺⁾ 
• 1005411-72-2 Br^(1-)*C₂₁H₂₆NO₆⁽¹⁺⁾ 
• 16590-41-3 Naltrexone 
• 1067643-85-9 methylnaltrexone-3-sulfate 

Relevant academic research and scientific papers

Preparation method of methylnaltrexone bromide

The invention discloses a preparation method of methylnaltrexone bromide. Naltrexone is used as an initial raw material, methylation is carried out by bromomethane, and a methylnaltrexone bromide crude product is obtained; and salt forming, acidifying and purification are carried out in order to prepare methylnaltrexone bromide. The method has the advantages of simple technological operation, scientific and reasonable processes, and high purity and yield of the product.

Preparation method for bromomethyl naltrexone

The invention specifically relates to a preparation method for bromomethyl naltrexone, belonging to the field of pharmaceutical chemicals. According to the invention, bromomethyl naltrexone is prepared from an intermediate, i.e., O-benzyl-N-bromomethyl na

Brominated morphinan quaternary ammonium salt preparation method

Disclosed is a preparation method for a morphinan bromide quaternary ammonium salt as represented by Formula (I). The method comprises: transforming a compound as represented by Formula (II) in a compound as represented by Formula (I) by an ion-exchange using a brominated strongly basic anion-exchange resin. The definitions of A, R1, R1 and X- found in Formula (I) and Formula (II) are as presented in the description.

Process for the preparation of quaternary n-alkyl morphinan alkaloid salts

An improved process for the N-alkylation of tertiary morphinan alkaloid bases to form the corresponding quaternary morphinan alkaloid derivatives.

Process for the Preparation of Quaternary N-Alkyl Morphinan Alkaloid Salts

An improved process for the N-alkylation of tertiary morphinan alkaloid bases to form the corresponding quaternary morphinan alkaloid derivatives.

METHOD FOR PRODUCING N-METHYLNALTREXONE BROMIDE

Process for the preparation of N-methylnaltrexone bromide, wherein a compound of the general formula (I): wherein X? represents an anion other than the bromide anion, and R represents hydrogen or a leaving group, is dissolved or dispersed in a suitable polar solvent, the solution or dispersion is mixed with a compound containing bromide anions, and the resulting reaction mixture is stirred until N-methylnaltrexone bromide has formed and crystallised, wherein, in the case where R represents a leaving group, that group is removed during or after the reaction.

CRYSTALLINE FORMS OF NALTREXONE METHOBROMIDE

The present invention relates to novel crystalline forms of naltrexone methobromide including hydrated and solvated forms. The invention also describes methods of preparing the various crystalline forms. The present invention also relates to pharmaceutical compositions containing crystalline forms of naltrexone methobromide, as well as methods of treating or preventing opioid induced side effects by administering the pharmaceutical compositions.

PROCESS FOR PREPARING N-ALKYLNALTREXONE HALIDES

The invention relates to a novel process for preparing N-methylnaltrexone bromide, comprising at least the steps consisting in: (i) reacting N-methylnaltrexone methyl sulfate in aqueous solution with an alkaline agent chosen from the group constituted by sodium carbonate, potassium carbonate, calcium carbonate, magnesium carbonate, cesium carbonate, strontium carbonate and mixtures thereof, for a pH of the aqueous reaction medium of between 7 and 10, and then in(ii) reacting the product thus obtained with hydrobromic acid, which is added for a pH of the aqueous reaction medium of between 0.5 and 5, in order thus to obtain the N-methylnaltrexone bromide.