1354744-91-4

Usage

Uses

Used in Pharmaceutical Industry:
Naloxegol Oxalate is used as a peripherally-selective opioid antagonist for the treatment of opioid-induced constipation in adults with chronic non-cancer pain. It functions by reducing the CNS penetration and inhibiting the binding of opioids in the gastrointestinal tract, providing relief from constipation without compromising the pain-relieving effects of opioids.

Synthesis

Naloxone (180) was treated with methoxyethyl chloride in the presence of Hunig’s base to give the protected ketone 181. Reduction of the ketone with potassium trisec- butylborohydride exclusively provided the a-alcohol 182 in 85% yield. Alternatively, sodium trialkylborohydrides could also be used to provide similar a-selective reduction in high yield. Deprotonation of the alcohol with sodium hydride followed by alkylation with CH3(OCH2CH2)7Br (183) provided the pegylated intermediate 184 in 88% yield. Acidic removal of the methoxyethyl ether protecting group followed by treatment with oxalic acid and crystallization provided naloxegol oxalate (XXI) in good yield.

Upstream product

• 854601-63-1 (4R,4aS,7aR,12bS)-3-allyl-9-((2-methoxyethoxy)methoxy)-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-4a,7-diol 
• 104518-25-4 22-bromo-2,5,8,11,14,17,20-heptaoxadocosane 
• 112-35-6 triethylene glucol monomethyl ether 
• 74654-05-0 8-methoxy-1-(methylsulfonyl)oxy-3,6-dioxaoctane 
• 112-60-7 Tetraethylene glycol 
• 854601-70-0 (5α,6α)-17-allyl-6-(2,5,8,11,14,17,20-heptaoxadocosan-22-yloxy)-4,5-epoxymorphinan-3,14-diol 
• 144-62-7 oxalic acid 
• 86259-87-2 1-phenyl-2,5,8,11-tetraoxatridecan-13-ol 
• 4437-01-8 3,6,9,12,15,18,21-heptaoxadocosan-1-ol 
• 477775-57-8 20-methoxy-1-(methylsulfonyl)oxy-3,6,9,12,15,18-hexaoxaeicosane 
• 357-08-4 naloxone hydrochloride 
• 854601-62-0 3-O-MEM-naloxone 
• 79622-11-0 2,5,8,11,14,17,20-heptaoxadocosan-22-yl 4-methylbenzene-1-sulfonate 

Relevant academic research and scientific papers

Naloxegol Oxalate and Solid Dispersion thereof

The present invention relates to solid dispersion of Naloxegol oxalate. Further, the present invention relates to an improved process for Naloxegol oxalate and intermediates thereof.

AN IMPROVED PROCESS FOR THE PREPARATION OF (5Α,6Α)-17-ALLYL-6-(2,5,8,11,14,17,20- HEPTAOXADOCOSAN-22-YLOXY)-4,5-EPOXYMORPHINAN-3,14-DIOL AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS

The present invention relates to an improved process for the preparation of (5α, 6α)-17-allyl-6-(2, 5, 8, 11, 14, 17, 20- heptaoxadocosan-22-yloxy)-4, 5-epoxymorphinan-3, 14-diol which is represented by the following structural formula-1 or its pharmaceut

Crystalized polyethylene glycol naloxone oxalate and preparation method

The invention provides novel crystal forms I and II of polyethylene glycol naloxone oxalate. An X-ray powder diffraction map of the two novel crystal forms include diffraction peaks shown by the angleof 2 theta, wherein the error range of the angle of 2 theta ranges from -0.2 to +0.2, the form I includes the peaks of 6.85 degrees, 13.85 degrees, 20.35 degrees, 22.64 degrees, 23.08 degrees, 24.67degrees and 26.15 degrees, and the form II includes the peaks of 7.01 degrees, 11.46 degrees, 12.89 degrees, 13.71 degrees, 14.95 degrees, 15.83 degrees, 17.55 degrees, 20.45 degrees, 21.96 degrees, 22.73 degrees, 25.78 degrees, 25.62 degrees, 26.21 degrees and 28.60 degrees. The invention further provides a preparation method of the novel crystal forms (I and II). The two crystal forms are simplein technology, easy to prepare, low in production cost and environmentally friendly, and has the good water solubility, purity and stability.

NALOXEGOL OXALATE AND SOLID DISPERSION THEREOF

The present invention relates to solid dispersion of Naloxegol oxalate. Further, the present invention relates to an improved process for Naloxegol oxalate and intermediates thereof.