Check patentability & draft patents in minutes with Patsnap Eureka AI!

Preparation method of paricalcitol isomer impurity PY5

A technology of paricalcitol and isomers, which is applied in the field of preparation of paricalcitol isomer impurity PY5, achieves the effects of easy control of conditions, easy availability of raw materials, accurate positioning and qualitative improvement

Pending Publication Date: 2019-10-15
NANJING HERON PHARMA SCI & TECH CO LTD
View PDF5 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] After searching, there is no literature report about the synthesis of this impurity, so it is of great practical significance to provide a preparation method for the impurity PY5 of the paricalcitol isomer, which is used for the preparation of the impurity reference substance of paricalcitol

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
  • Preparation method of paricalcitol isomer impurity PY5
  • Preparation method of paricalcitol isomer impurity PY5
  • Preparation method of paricalcitol isomer impurity PY5

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] The preparation of embodiment 1 formula 3 compound

[0038] Add about 5g of compound 2 and 160mL of methanol into the reaction flask, add 2g of sodium methoxide in batches, and keep at 20-30°C for 16-17h. After the reaction is complete, add 400mL of water to the system, and extract twice with ethyl acetate, each 400 mL, combined the organic phases, washed with 200 mL of water and 200 mL of saturated brine, concentrated to dryness, purified on a 100-200 mesh silica gel column, and eluted with n-hexane: ethyl acetate = 40:1 to obtain about 3.78 g of compound 3. ESI-MS (m / z): 429.75[M+Na] +

Embodiment 3

[0039] The preparation of embodiment 3 formula 5 compounds

[0040] Under argon protection, compound 4, namely [2-[(3R,5R-3,5-bis[tert-butyldimethylsilyloxy]cyclohexene]ethyl]diphenylphosphine was added to the reaction flask 6.5g and 400mL of anhydrous tetrahydrofuran, stirring and cooling down to -60~-70°C, adding 7mL of sodium bis(trimethylsilyl)amide dropwise under temperature control, keeping the reaction for 1h after dropping, adding about 4g of compound 3 in anhydrous Tetrahydrofuran 50mL solution. After dropping, react at 0-5°C. After the reaction is complete, add 500mL of water to the system, extract with 800mL of ethyl acetate, combine the organic phases, wash with 400mL of water, wash with 400mL of saturated saline, concentrate to dryness, 100-200 mesh Silica gel column purification, eluting with n-hexane: ethyl acetate = 50:1 gave about 2.3 g of compound 5.

[0041] The preparation of embodiment 4 formula 1 compound crude product

[0042] Add about 2.3 g of compou...

Embodiment 6

[0049] The paricalcitol isomer impurity PY5 is used as the impurity reference substance to check the related substances in the paricalcitol bulk drug, which specifically includes the following steps:

[0050] 1. The following chromatographic operations are suitable for the content determination of paricalcitol related substances.

[0051] 2. Chromatographic conditions

[0052] Chromatographic column: use octadecylsilane bonded silica gel as filler (4.6mm×100mm, 2.7μm);

[0053] Column temperature: 30°C;

[0054] Mobile phase: acetonitrile-water (50:950) as mobile phase A, acetonitrile-methanol (750:250) as mobile phase B, for linear gradient elution; running time: 40min;

[0055] Flow rate: 0.9ml / min;

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 invention discloses a preparation method of paricalcitol isomer impurity PY5. The preparation method comprises the following steps: taking (1R, 3aR, 7aR)-1-((2R,5R,E)-5,6-dimethyl heptyl-3-alkene-2-yl)-7a-methyl octahydro-4H-indole-4-ketone as a starting material, performing isomerization, butt-joint, deprotection, recrystallization and like steps to acquire a high-purity paricalcitol isomer impurity PY5, wherein the paricalcitol isomer impurity PY5 belongs to the field of the chemical and biological pharmacy. The impurity can be used as paricalcitol finished product to detect and analyze,thereby realizing the accurate positioning and nature-determination of the impurity; the control on the impurity can be reinforced, and then the quality of the paricalcitol finished product and the preparation can be improved.

Description

technical field [0001] The invention belongs to the field of chemistry and biopharmaceuticals, and in particular relates to a preparation method of a paricalcitol isomer impurity PY5. Background technique [0002] Paricalcitol is a selective, third-generation vitamin D receptor activator developed by Abbott. As an active vitamin D therapeutic drug, it can selectively activate vitamin D receptor (VDR) and select Sexually up-regulate the calcium-sensitive receptor (CaSR) in the thyroid, which can better and more efficiently inhibit the synthesis and secretion of PHT in patients with uremia. Drugs for the prevention and treatment of secondary hyperparathyroidism (SHPT) in patients with stage III and IV chronic kidney disease (CKD). Its structural formula is as shown in formula I: [0003] [0004] Paricalcitol is unstable in nature, sensitive to light and heat, contains multiple chiral centers, and has a long synthetic route. During the synthetic process, some isomer impur...

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
IPC IPC(8): C07F7/12C07C29/00C07C35/21C07C29/78
CPCC07F7/127C07C29/00C07C29/78C07C2602/08C07C35/21Y02P20/55
Inventor 郭彦飞胡情姣张万朝丁伯祥
Owner NANJING HERON PHARMA SCI & TECH CO LTD
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