491833-28-4

Basic information

• Product Name: 1-Pyrrolidinepropanol, β-amino-α-(2,3-dihydro-1,4-benzodioxin-6-yl)-, (αR,βR)-
• Synonyms: 1-Pyrrolidinepropanol, β-amino-α-(2,3-dihydro-1,4-benzodioxin-6-yl)-, (αR,βR)-;Eliglustat intermediate 5;(1R,2R)-2-amino-1-(2,3-dihydrobenzo[beta][1,4]dioxin-6-yl)-3-pyrrolidin-1-yl-propan-1-ol;(1R,2R)-2-AMINO-1-(2,3-DIHYDRO-1,4-BENZODIOXIN-6-YL)-3-(PYRROLIDIN-1-YL)PROPAN-1-OL
• CAS NO: 491833-28-4
• Molecular Formula: C₁₅H₂₂N₂O₃
• Molecular Weight: 278.34678
• Mol File: 491833-28-4.mol
• Article Data: 21

Chemical Properties

• Boiling Point: 471.2±45.0 °C(Predicted)
• Appearance: /
• Density: 1.232±0.06 g/cm3(Predicted)
• PKA: 11.75±0.45(Predicted)
• CAS DataBase Reference: 1-Pyrrolidinepropanol, β-amino-α-(2,3-dihydro-1,4-benzodioxin-6-yl)-, (αR,βR)-(CAS DataBase Reference)
• NIST Chemistry Reference: 1-Pyrrolidinepropanol, β-amino-α-(2,3-dihydro-1,4-benzodioxin-6-yl)-, (αR,βR)-(491833-28-4)
• EPA Substance Registry System: 1-Pyrrolidinepropanol, β-amino-α-(2,3-dihydro-1,4-benzodioxin-6-yl)-, (αR,βR)-(491833-28-4)

Safety Data

• Hazardous Substances Data: 491833-28-4(Hazardous Substances Data)

Usage

General Description

1-Pyrrolidinepropanol, β-amino-α-(2,3-dihydro-1,4-benzodioxin-6-yl)-, (αR,βR)- is a chemical compound with potential pharmaceutical and medicinal applications. It is a β-amino alcohol derivative that contains a pyrrolidine ring and a 2,3-dihydro-1,4-benzodioxin-6-yl group. 1-Pyrrolidinepropanol, β-amino-α-(2,3-dihydro-1,4-benzodioxin-6-yl)-, (αR,βR)- is chiral, with the (αR,βR)- configuration. It may have biological activity as a potential drug candidate or as a building block for the synthesis of other bioactive compounds. Further research and testing are necessary to determine its specific pharmacological properties and potential uses in the field of medicine.

Upstream product

• 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 
• 4442-54-0 2,3-dihydro-1,4-benzodioxin-6-carboxylic acid 
• 14939-91-4 (E)-3,4-ethylenedioxycinnamic acid 

Downstream Products

• 245329-78-6 D-threo-1-(3',4'-ethylenedioxy)phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol 
• 491833-29-5 (1R,2R)-octanoic acid [2-(2',3'-dihydro-benzo[1,4]dioxin-6'-yl)-2-hydroxy-1-pyrrolidin-1-ylmethyl-ethyl]-amide 
• 491833-30-8 eliglustat 

Relevant articles and documents

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.

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.

Optimization of Eliglustat-Based Glucosylceramide Synthase Inhibitors as Substrate Reduction Therapy for Gaucher Disease Type 3

There remain no approved therapies for rare but devastating neuronopathic glyocosphingolipid storage diseases, such as Sandhoff, Tay-Sachs, and Gaucher disease type 3. We previously reported initial optimization of the scaffold of eliglustat, an approved therapy for the peripheral symptoms of Gaucher disease type 1, to afford 2, which effected modest reductions in brain glucosylceramide (GlcCer) in normal mice at 60 mg/kg. The relatively poor pharmacokinetic properties and high Pgp-mediated efflux of 2 prompted further optimization of the scaffold. With a general objective of reducing topological polar surface area, and guided by multiple metabolite identification studies, we were successful at identifying 17 (CCG-222628), which achieves remarkably greater brain exposure in mice than 2. After demonstrating an over 60-fold improvement in potency over 2 at reducing brain GlcCer in normal mice, we compared 17 with Sanofi clinical candidate venglustat (Genz-682452) in the CBE mouse model of Gaucher disease type 3. At doses of 10 mg/kg, 17 and venglustat effected comparable reductions in both brain GlcCer and glucosylsphingosine. Importantly, 17 achieved these equivalent pharmacodynamic effects at significantly lower brain exposure than venglustat.

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.