Supercharge Your Innovation With Domain-Expert AI Agents!

Pitavastatin calcium intermediate diastereomer and preparation method thereof

A technology of diastereomer, pitavastatin calcium, applied in the field of medicinal chemistry

Inactive Publication Date: 2019-02-26
北京亦度正康健康科技有限公司
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] After searching, there is no report about the diastereoisomer compound Ⅰ of pitavastatin calcium intermediate in the public literature at present

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
  • Pitavastatin calcium intermediate diastereomer and preparation method thereof
  • Pitavastatin calcium intermediate diastereomer and preparation method thereof
  • Pitavastatin calcium intermediate diastereomer and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] (5S,6E)-7-[2-Cyclopropyl-4-(4-fluorophenyl)-3-quinolinyl]-3-oxo-5-hydroxy-6-heptenoic acid tert-butyl ester ( Compound Ⅲ) Preparation

[0029] Hexamethyldiazasilane (25.42g) was added to dry THF (100ml). -10℃ drop 2.5mol·L -1 The n-butyl lithium n-hexane solution (15.8 ml) was stirred at -10°C for 30 min. Cool to -30°C, add (S)-(-)-HYTRA (5.24g), and stir at -25°C for 30 min. After cooling to -78°C, 3-(2-cyclopropyl-4-(4-fluorophenyl)-3-quinolinyl)prop-2-enal (5.0g) in THF (20ml) was added dropwise, Stirring was continued for 1 h at -78°C. Drop 2.5mol·L -1 N-Butyllithium n-hexane solution (31.5ml, 78.75mmol), continue stirring at -78°C for 30min, add tert-butyl acetate (10.16ml, 78.75mmol) dropwise, stir at -78°C for 1h, warm to 0°C and stir for 1h. The reaction was quenched by adding water (100ml), concentrated hydrochloric acid was adjusted to pH7, extracted with ethyl acetate (50ml×2), the organic layers were combined, the solvent was evaporated under reduced pressu...

Embodiment 2

[0031] (3S,5S,6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolinyl]-3,5-dihydroxy-6-heptenoic acid tert-butyl ester ( Preparation of compound Ⅱ)

[0032] Dissolve tetramethyltriacetoxyborazine (16.88g) and acetic acid (60ml) in acetonitrile (60ml) in sequence, stir at room temperature for 30min, cool to -15°C, and add compound III (6.10g) in acetonitrile (60ml) ) And acetic acid (20ml) solution, continue to stir for 3h. Saturated sodium bicarbonate solution was added to adjust pH 8, and methyl tert-butyl ether (200ml×2) was extracted. The organic layer was evaporated under reduced pressure to remove the solvent to obtain a pale yellow oily compound II (4.95g).

Embodiment 3

[0034] (3S,5S,6E)-7-[2-Cyclopropyl-4-(4-fluorophenyl)-3-quinolinyl]-3,5-dihydroxy-3,5-O-isopropylidene Of tert-butyl 6-heptenoate (Compound Ⅰ)

[0035] (3S, 5S, 6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolinyl]-3,5-dihydroxy-6-heptenoic acid tert-butyl ester (4.5g) dissolved in 2,2-dimethoxypropane completely dissolved (in 45ml), added p-toluenesulfonic acid monohydrate (0.6g), stirred at room temperature for 2h, the reaction solution was evaporated to dryness under reduced pressure, and the residue was passed through silica gel Purification by column chromatography [eluent: n-hexane: ethyl acetate (10:1)] gave the target compound I (3.8 g) as a pale yellow solid.

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 belongs to the field of medicinal chemistry, and relates to a pitavastatin calcium intermediate diastereomer (3S,5S isomer), ie., (3S,5S,6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]-3,5-dihydroxy-3,5-O-isopropylidene-6-tert-butyl heptenoate. The invention further relates to a preparation method of the pitavastatin calcium intermediate diastereomer (3S, 5S isomer), and uses ofthe pitavastatin calcium intermediate diastereomer (3S, 5S isomer) in detection of the purity of the pitavastatin calcium intermediate or the content of the optical isomer and control of the quality of the intermediate during the production or preparation of pitavastatin calcium.

Description

Technical field [0001] The present invention belongs to the field of medicinal chemistry. Specifically, the present invention relates to a diastereomer (3S, 5S type isomer) of pitavastatin calcium intermediate (3S, 5S, 6E)-7-[2- Cyclopropyl-4-(4-fluorophenyl)-3-quinolinyl]-3,5-dihydroxy-3,5-O-isopropylidene-6-heptenoic acid tert-butyl ester. The invention also relates to a method for preparing the diastereomers (3S, 5S isomers) of the pitavastatin calcium intermediate and its use. Background technique [0002] Pitavastatin Calcium is a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor jointly developed by Sanka Chemical Industry Co., Ltd. and Japan Kowa Co., Ltd., in 2003 It was first put on the market in Japan in 1999. It is mainly adapted to hypercholesterolemia. It is called "super statin" because of its good cholesterol lowering effect. The structural formula of pitavastatin calcium is as follows: [0003] [0004] Patent literature has reported the synthes...

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): C07D405/06
CPCC07D405/06C07B2200/07
Inventor 李纬王正泽林辉
Owner 北京亦度正康健康科技有限公司
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