Naloxegol Oxalate

Base Information

• Chemical Name: Naloxegol Oxalate
• CAS No.: 1354744-91-4
• Molecular Formula: C34H53NO11.C2H2O4
• Molecular Weight: 741.8196
• Mol file: 1354744-91-4.mol

Synonyms:Naloxegol Oxalate;Naloxegol Oxalate NKTR-118;(5alpha,6alpha)-4,5-Epoxy-6-(3,6,9,12,15,18,21-heptaoxadocos-1-yloxy)-17-(2-propen-1-yl)-morphinan-3,14-diol ethanedioate;AZ 13337019 oxalate;NKTR 118 oxalate

Chemical Property of Naloxegol Oxalate

Chemical Property:

• PSA: 201.37000
• LogP: 0.95700
• Storage Temp.: -20°C Freezer, Under inert atmosphere
• Solubility.: Chloroform (Slightly), Methanol (Slightly)

Purity/Quality:

99% ^*data from raw suppliers

NaloxegolOxalate ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: Naloxegol oxalate (XXI) is a peripherally acting μ-opioid receptor antagonist that was approved in the USA and EU for the treatment of opioid-induced constipation in adults with chronic non-cancer pain. The drug, a pegylated version of naloxone, has significantly reduced central nervous system (CNS) penetration and works by inhibiting the binding of opioids in the gastrointestinal tract. Naloxegol oxalate was developed by Nektar and licensed to AstraZeneca. Although we were unable to find a single report in the primary or patent literature that describes the exact experimental procedures to prepare naloxegol oxalate, there have been reports on the preparation of closely related analogs with specific reports on improving the selectivity of the reduction step156 and the salt formation of the final drug substance.
• Uses: Naloxegol Oxalate is an oxalate form of Naloxegol (N284470) which is a peripherally-selective opioid antagonist.

Technology Process of Naloxegol Oxalate

There total 19 articles about Naloxegol Oxalate which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 95.0%

(5α,6α)-17-allyl-6-(2,5,8,11,14,17,20-heptaoxadocosan-22-yloxy)-4,5-epoxymorphinan-3,14-diol (854601-70-0) + oxalic acid (144-62-7,97993-78-7) → naloxegol oxalate (1354744-91-4)

Guidance literature:

In methanol; at 20 - 35 ℃; for 0.5h;

Reference yield:

triethylene glucol monomethyl ether (112-35-6,95507-80-5) → naloxegol oxalate (1354744-91-4)

Guidance literature:

Multi-step reaction with 9 steps

1.1: triethylamine / dichloromethane / 1 h / 0 - 30 °C

2.1: potassium hydroxide / tetrahydrofuran / 0.5 h / 60 - 70 °C

2.2: 24 h / Reflux

3.1: hydrogenchloride; pyrographite; palladium 10% on activated carbon; hydrogen / water; ethanol / 4 h / Autoclave

4.1: triethylamine / dichloromethane / 1.5 h / 0 - 30 °C

5.1: tetrabutylammomium bromide / toluene / 2 h / 20 - 85 °C

6.1: sodium hydride / toluene; N,N-dimethyl-formamide / 1 h / 5 - 10 °C / Inert atmosphere

6.2: 8 - 16 °C / Inert atmosphere

6.3: 15 - 20 °C

7.1: sodium carbonate / dichloromethane; water / 0.33 h / 20 - 30 °C

8.1: hydrogenchloride; 2,6-di-tert-butyl-4-methyl-phenol / ethyl acetate / 1.5 h / 10 - 15 °C

9.1: propan-1-ol; tert-butyl methyl ether

With hydrogenchloride; 2,6-di-tert-butyl-4-methyl-phenol; palladium 10% on activated carbon; tetrabutylammomium bromide; hydrogen; sodium hydride; sodium carbonate; pyrographite; triethylamine; potassium hydroxide; In tetrahydrofuran; propan-1-ol; ethanol; dichloromethane; tert-butyl methyl ether; water; ethyl acetate; N,N-dimethyl-formamide; toluene;

Reference yield:

8-methoxy-1-(methylsulfonyl)oxy-3,6-dioxaoctane (74654-05-0) → naloxegol oxalate (1354744-91-4)

Guidance literature:

Multi-step reaction with 8 steps

1.1: potassium hydroxide / tetrahydrofuran / 0.5 h / 60 - 70 °C

1.2: 24 h / Reflux

2.1: hydrogenchloride; pyrographite; palladium 10% on activated carbon; hydrogen / water; ethanol / 4 h / Autoclave

3.1: triethylamine / dichloromethane / 1.5 h / 0 - 30 °C

4.1: tetrabutylammomium bromide / toluene / 2 h / 20 - 85 °C

5.1: sodium hydride / toluene; N,N-dimethyl-formamide / 1 h / 5 - 10 °C / Inert atmosphere

5.2: 8 - 16 °C / Inert atmosphere

5.3: 15 - 20 °C

6.1: sodium carbonate / dichloromethane; water / 0.33 h / 20 - 30 °C

7.1: hydrogenchloride; 2,6-di-tert-butyl-4-methyl-phenol / ethyl acetate / 1.5 h / 10 - 15 °C

8.1: propan-1-ol; tert-butyl methyl ether

With hydrogenchloride; 2,6-di-tert-butyl-4-methyl-phenol; palladium 10% on activated carbon; tetrabutylammomium bromide; hydrogen; sodium hydride; sodium carbonate; pyrographite; triethylamine; potassium hydroxide; In tetrahydrofuran; propan-1-ol; ethanol; dichloromethane; tert-butyl methyl ether; water; ethyl acetate; N,N-dimethyl-formamide; toluene;

upstream raw materials:

(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

22-bromo-2,5,8,11,14,17,20-heptaoxadocosane

triethylene glucol monomethyl ether

8-methoxy-1-(methylsulfonyl)oxy-3,6-dioxaoctane

Refernces

• 1、 -. "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". . . Retrieved 2019/04/16.
• 2、 -. "NALOXEGOL OXALATE AND SOLID DISPERSION THEREOF". . . Retrieved 2018/06/12.