491833-29-5

Basic information

• Product Name: Eliglustat
• Synonyms: Eliglustat;Genz 99067;N-[(1R,2R)-2-(2,3-Dihydro-1,4-benzodioxin-6-yl)-2-hydroxy-1-(1-pyrrolidinylmethyl)ethyl]-octanamide;N-[(1R,2R)-1-(2,3-Dihydro-1,4-benzodioxin-6-yl)-1-hydroxy-3-(1- pyrrolidinyl)-2-propanyl]octanamide;Eliglustat(Genz-99067)
• CAS NO: 491833-29-5
• Molecular Formula: C₂₃H₃₆N₂O₄
• Molecular Weight: 404.54294
• Mol File: 491833-29-5.mol

Chemical Properties

• Boiling Point: 615.5±55.0 °C(Predicted)
• Appearance: /
• Density: 1.123±0.06 g/cm3(Predicted)
• Storage Temp.: 2-8°C
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 13.45±0.20(Predicted)
• CAS DataBase Reference: Eliglustat(CAS DataBase Reference)
• NIST Chemistry Reference: Eliglustat(491833-29-5)
• EPA Substance Registry System: Eliglustat(491833-29-5)

Safety Data

• Hazardous Substances Data: 491833-29-5(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Eliglustat is used as a therapeutic agent for the treatment of Gaucher's disease. It works by inhibiting the enzyme glucosylceramide synthase, which is responsible for the synthesis of glucosylceramide. This inhibition helps to reduce the accumulation of glucosylceramide in the body, providing relief from the symptoms associated with Gaucher's disease.
Used in Research and Development:
Eliglustat is also used as a research tool in the study of glucosylceramide synthase and its role in various cellular processes. It can be employed to investigate the effects of inhibiting this enzyme on cellular functions and to develop a better understanding of the underlying mechanisms of Gaucher's disease and other related conditions.

Upstream product

• 14464-30-3 2,5-dioxopyrrolidin-1-yl octanoate 
• 491833-28-4 (1R,2R)-2-amino-1-(2,3-dihydrobenzo[β][1,4]dioxin-6-yl)-3-pyrrolidin-1-yl-propan-1-ol 
• 2879-20-1 1,4-benzodioxan-6-yl methyl ketone 
• 35970-31-1 2-amino-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)ethan-1-one hydrochloride 
• 4629-54-3 2-bromo-1-(2,3-dihydro-1,4-benzodioxin-6-yl)ethanone 
• 1282295-32-2 C₁₂H₁₀N₂O₃ 
• 6761-70-2 2,3-dihydro-1,4-benzodioxine-6-carbonyl chloride 
• 74053-94-4 ethyl 3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-3-oxopropanoate 

Relevant articles and documents

A novel method for preparing Eligulstat through chiral resolution

Eliglustat is a ceramide glucosyltransferase inhibitor work as first line oral therapy for adults with Gaucher disease type 1 (a rare disease) at present. Although the eliglustat in enantiomerically pure forms is obtained by asymmetric syntheses, the reported methods suffer from many limits when it comes to industrial applications. Therefore, the preparation of a racemic mixture followed by resolution can still be a viable and straightforward alternative, especially when it could be adapted to large scale. Herein, we developed an effective and practical synthetic route to prepare stereoisomers mixture of eliglustat, and a novel chiral resolution method to prepare eliglustat. Using 1,1′-Binaphthyl-2,2′-diyl -hydrogenphosphate (BNDHP) as resolution reagent, optical pure eliglustat (e.e. >99%, 13.97% total yield) could be obtained after recrystallization.

AN IMPROVED PROCESS FOR THE PREPARATION OF ELIGLUSTAT AND ITS INTERMEDIATE

The present invention relates to an improved process for the preparation of N-((1R,2R)-1-(2,3- dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)octanamide (A), which is known as ELIGLUSTAT and its pharmaceutically acceptable salts, comprising the formation of novel intermediate metal complex (III), which on hydrolysis in presence of acid provides amine compound (IV) (as described herein), which is treated with pyrrolidine and subsequently reduced to convert into Eliglustat (A).

Eliglustat intermediate and preparation method thereof

The invention relates to an eliglustat intermediate and a preparation method thereof, and provides a series of intermediate compounds for preparing eliglustat, and a preparation method of the intermediates. With the method provided by the invention, raw materials and a transition metal catalyst are subjected to an asymmetric hydrogenation reaction on under certain conditions, and then a series ofreactions are performed to prepare eliglustat. The method provided by the invention is simple and controllable in reaction conditions and easy for industrial production.

Preparation method of gaucher disease treatment drug eliglustat

The invention relates to a preparation method of a gaucher disease treatment drug eliglustat. The preparation method comprises the following steps: using S-isopropyl-2-oxazolidinone as a raw material,carrying out a condensation reaction, a bromination reaction, a substitution reaction, a hydrolysis reaction, a condensation reaction and a reduction reaction to obtain eliglustat, and carrying out salt forming and two-step purification on the eliglustat to obtain high-purity eliglustat tartrate. According to the method, the chiral center is completely synthesized from the starting material, so that the reaction steps are reduced, the production period is shortened, the synthesis efficiency of the chiral center is improved, the yield of the final product is improved, the salt forming steps are optimized in detail, and the qualified quality control of the bulk drug is ensured.

Development of an Efficient and Scalable Asymmetric Synthesis of Eliglustat via Ruthenium(II)-Catalyzed Asymmetric Transfer Hydrogenation

An efficient and scalable synthesis of eliglustat (1) is herein reported. This novel route features a three-step telescoped process to afford the α-dibenzylamino β-ketoester 6 in 85% overall yield from commercially available 1,4-benzodioxane-6-carboxylic acid 7. The key intermediate 5 was obtained via an efficient ruthenium-catalyzed DKR-ATH reaction, which afforded the desired product in 90% isolated yield with >99:1 dr and 99.7% ee on a 100 g scale. In addition, the amidation of sterically hindered carboxylic acid 14 was optimized and amenable to scale-up. This process not only gives a desirable total yield but also avoids hazardous conditions and chromatographic purification. The robustness of this synthesis was successfully performed on a multigram scale to afford 1 with >99.9% de and >99.9% ee in 56.8% overall yield in nine steps.

STABLE N-((1R,2R)-1-(2,3-DIHYDROBENZO[B][1,4]DIOXIN-6-YL)-1-HYDROXY-3-(PYRROLIDIN-1-YL)PROPAN-2-YL) OCTANAMIDE (2R,3R)-2,3-DIHYDROXYSUCCINATE PREMIX AND PROCESS FOR PREPARATION THEREOF

The present invention related to stable N-((1R, 2R)-1-(2,3-dihydrobenzo[b][1,4] dioxin-6-yl)- 1-hydroxy-3- (pyrrolidin-1-yl)propan-2-yl) octanamide (2R,3R)- 2,3-dihydroxysuccinate premix of formula (Ia) and its process for preparation thereof. The present invention also related to process for the preparation of N-((1R, 2R)-1-(2,3-dihydrobenzo[b][1,4] dioxin-6- yl)-1-hydroxy-3- (pyrrolidin-1-yl) propan-2-yl) octanamide of formula (I) and pharmaceutically acceptable salts.

Concise and efficient synthesis of eliglustat

Eliglustat, a ceramide glucosyltransferase inhibitor, was synthesized in six steps with 28.4% overall yield. The key features include the use of a diastereoselective aldol reaction to construct two contiguous stereocenters and a selective sulfonylation of a 1,3-diol catalyzed by dibutyltin oxide.

Method for preparing Eliglustat

The invention discloses a method for preparing Eliglustat. The Eliglustat is an effective specific glucosylceramide systhase inhibitor, which can be used for treating type-I Gaucher disease. The invention provides the synthetic method of Eliglustat, which comprises the following steps: 1,4-benzdioxan-6-formaldehyde and a chiral ligand are subjected to an adiastereoselectivity Aldol reaction, and then subjected to a reduction reaction, replacement and a Staudinger reaction, and an amidation reaction to obtain Eliglustat. The method has the advantages of easy acquisition of raw material, simpleoperation, high product yield and purity, and easy industrial large production.

Synthesis of UDP-glucose: N-acylsphingosine glucosyl transferase inhibitors

Disclosed is a novel enantiomeric synthesis ceramide-like inhibitors of UDP-glucose: N-acylsphingosine glucosyltransferase. Also disclosed are novel intermediates formed during the synthesis.

IMPROVED PROCESS FOR THE PREPARATION OF ELIGLUSTAT AND ITS SALTS

The present application relates to an improved process for the preparation of Eliglustat or its pharmaceutically acceptable salts thereof. Further relates to isolation of intermediates in the form of solid and their use for preparation of Eliglustat or its pharmaceutically acceptable salts thereof.