Unlock instant, AI-driven research and patent intelligence for your innovation.

Beraprost-314d crystals and methods for preparation thereof

A technology of beraprost and -314d, which is applied in the fields of organic chemistry methods, drug combinations, cardiovascular system diseases, etc., can solve the uncertain whether there is crystal form I transformation of beraprost-314d, unrevealed beraprost - 314d crystal form I stability data, unable to evaluate, etc.

Active Publication Date: 2020-06-02
CHIROGATE INT
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, WO 2017 / 174439 does not disclose the stability data of Beraprost-314d crystalline form I, and it is uncertain whether there is a crystalline form transformation of Beraprost-314d crystalline form I
Therefore, the benefit of conventional crystallization methods for the preparation of stable beraprost-314d crystals cannot be assessed based on the prior art

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Beraprost-314d crystals and methods for preparation thereof
  • Beraprost-314d crystals and methods for preparation thereof
  • Beraprost-314d crystals and methods for preparation thereof

Examples

Experimental program
Comparison scheme
Effect test

example

[0068] X-Ray Powder Diffraction (XRPD) Analysis: XRPD patterns were collected on a Bruker D2 PHASER diffractometer with fixed divergence slit and ID LYNXEYE detector. The sample (approximately 100 mg) was placed flat on the sample holder. Use CuK α Radiation The as-prepared samples were analyzed at an energy of 10 mA and 30 kV over a 2Θ range of 5° to 50° with a step size of 0.02 degrees and a step time of 1 second. Removal of CuK by Diverging Beam Nickel Filter β radiation.

[0069] Differential Scanning Calorimetry (DSC) Analysis: DSC traces were collected on a TA DISCOVERY DSC25 instrument. Samples (approximately 5 mg) were weighed into aluminum pans with crimped closed aluminum lids. The prepared samples were analyzed from 10°C to 100°C at a scan rate of 10°C / min under nitrogen flow (approximately 50ml / min). The melting temperature and heat of fusion were calibrated by indium (In) before measurement.

example 1

[0071] Preparation of Crude Beraprost-314d

[0072] 2,3,3a,8b-tetrahydro-2-hydroxy-1-(3-hydroxy-4-methyl-1-octen-6-ynyl)-1H-cyclopenta[b]benzofuran- 5-Butyric acid methyl ester (50.0 g, 121.2 mmol) was dissolved in 200 ml of methanol, followed by the addition of 200 ml of 1 N sodium hydroxide / water solution and stirred for 2 hours. The reaction mixture was separated by acid-base extraction, and the solvent was evaporated under vacuum. The crude product was purified by silica gel chromatography using a mixture of hexane and ethyl acetate as gradient eluent to obtain 33.2 g of crude Beraprost-314d.

example 2

[0074] Preparation of Beraprost-314d Crystalline Form II

[0075]Crude beraprost-314d (1.00 g from Example 1) and ethyl acetate (10 ml) were heated to 40°C to dissolve and then cooled to room temperature. n-Hexane (20 ml) was slowly added dropwise, and the mixture was stirred in an ice-water bath for 18 hours until solid precipitation occurred. Afterwards, the resulting suspension was filtered and washed, followed by drying under high vacuum at room temperature for 24 hours, yielding 0.75 g of Beraprost-314d crystalline Form II. XRPD and DSC results with figure 1 and figure 2 same as shown in .

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The present invention provides crystalline Forms II and III of Beraprost-314d, and processes for the preparation thereof.

Description

technical field [0001] The present invention relates generally to solid forms of prostacyclin derivatives, and in particular to solid crystalline forms of Beraprost-314d and processes for their preparation. Background technique [0002] Beraprost is a synthetic benzoprostacycline analogue of natural prostacyclin consisting of four isomers (beraprost-314d, the anti-palm isomer of beraprost-314d, beraprost-315d and beraprost-315d anti-palm isomer) composition, as shown in the following structural formula. Among them, optically pure beraprost-314d (known as Esuberaprost, APS-314d or BPS-314d) is a pharmacologically active isomer currently undergoing clinical trials in North America and Europe as an inhaled Treprostinil Additional active pharmaceutical ingredients for the treatment of diseases such as pulmonary arterial hypertension. The preparation of beraprost-314d has been disclosed in prior art such as Heterocycles, 2000, 53, 1085-1092, US8779170 and WO 2017 / 174439. [...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07D307/93
CPCC07D307/93C07B2200/13A61P9/00C07D209/80C07D307/79
Inventor 魏士益郑建邦
Owner CHIROGATE INT
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com