Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

The synthetic method of bimatoprost

The technology of a kind of bimatoprost, synthetic method, is applied in the synthetic field of bimatoprost, can solve the problems such as the total yield of bimatoprost is not high, the stability of synthetic intermediate is poor, side reaction easily occurs, and avoids column Chromatographic process, easy operation, less side effects

Active Publication Date: 2022-04-19
GUANGZHOU KEMROCMED CO LTD
View PDF8 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] In the existing method for synthesizing bimatoprost, in the process of synthesis, due to the existence of hydroxyl groups, the stability of the synthetic intermediate is poor, side reactions are prone to occur, the yield of each step is low, and it is difficult to purify
Even if the hydroxyl group is protected, there are generally low reaction yields and many by-products, so that the total yield of bimatoprost is not high

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
  • The synthetic method of bimatoprost
  • The synthetic method of bimatoprost
  • The synthetic method of bimatoprost

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Embodiment 1: the synthesis of bimatoprost

[0054] Taking coli lactone (1) as raw material to synthesize bimatoprost, the reaction scheme is as follows:

[0055]

[0056] (1) Synthesis of compound 2a

[0057]

[0058] Add TBSCl (52.6g, 350mmol, 3.0eq) and imidazole (25.0g, 360mmol, 3.0eq) to a solution of coli lactone (20g, 116.2mmol) in dichloromethane (200ml), react at room temperature for 8h, and filter with suction 10% hydrochloric acid solution (80mL) was added to the organic phase, then reacted at room temperature for 5h, quenched the reaction with saturated ammonium chloride solution (150ml), concentrated, added dichloromethane (200ml) and water (200ml), and stood to separate layers , the aqueous phase was extracted with dichloromethane (150ml*3), washed with saturated brine (100ml), dried over anhydrous sodium sulfate, filtered, concentrated, and recrystallized with ethyl acetate (180ml) to obtain white solid compound 2 (27.4g, 83%). 1 H NMR (400MHz, C...

Embodiment 2

[0077] Embodiment 2: the synthesis of bimatoprost

[0078] (1) Synthesis of compound 2a

[0079]

[0080] Add TBSCl (52.6g, 350mmol, 3.0eq) and potassium carbonate (49.6g, 360mmol, 3.0eq) to a solution of coli lactone (20g, 116.2mmol) in dichloromethane (200ml), react at room temperature for 8h, and filter with suction 10% hydrochloric acid solution (80mL) was added to the organic phase, then reacted at room temperature for 5h, quenched the reaction with saturated ammonium chloride solution (150ml), concentrated, added dichloromethane (200ml) and water (200ml), and stood to separate layers , the aqueous phase was extracted with dichloromethane (150ml*3), washed with saturated brine (100ml), dried over anhydrous sodium sulfate, filtered, concentrated, and recrystallized with ethyl acetate (180ml) to obtain white solid compound 2 (24.7g, 75%).

[0081] (2) Synthesis of Compound 3a

[0082]

[0083] At a temperature of 0°C, add PCC oxidant (31.1g, 90mmol, 1.5eq) to a sol...

Embodiment 3

[0099] The synthesis of embodiment 3 bimatoprost

[0100] (1) Synthesis of compound 2b

[0101]

[0102] For the synthesis method, refer to the synthesis of 2a in Example 1. (white solid) 1 H NMR (400MHz, CDCl 3 ):δ4.25(brs,OH),4.13(dd,J=9.2Hz,J=2.3Hz,1H),3.56-3.33(m,3H),2.37-2.08(m,3H),1.80-1.83( m,2H),1.42(m,1H),0.95(t,J=6.6Hz,9H),0.66(q,J=6.6Hz,6H)ppm.MS(m / z):287(M + +1).

[0103] (2) Synthesis of compound 3b

[0104]

[0105] For the synthesis method, refer to the synthesis of 3a in Example 1. 1 H NMR (400MHz, CDCl 3 ):δ9.71(s,1H),4.15(dd,J=9.2Hz,J=2.5Hz,1H),3.58(m,1H),2.37-2.12(m,4H),2.05-1.83(m, 2H), 0.96(t, J=6.6Hz, 9H), 0.67(q, J=6.6Hz, 6H)ppm.MS(m / z): 285(M + +1).

[0106] (3) Synthesis of compound 4b

[0107]

[0108] For the synthesis method, refer to the synthesis of 4a in Example 1. 1 H NMR (400MHz, CDCl 3 ):δ7.29-7.16(m,5H),5.68-5.55(m,2H),3.25-3.17(m,2H),2.62(t,J=6.8Hz,2H),2.11-1.75(m,8H ),0.96(t,J=6.6Hz,18H),0.66(q,J=6.6Hz,6H)ppm.MS(m / z):...

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 relates to a synthesis method of bimatoprost, which belongs to the technical field of chemical synthesis. The method adopts the following synthetic route different from the conventional technology to synthesize doxazosin, which provides a new synthetic route for the preparation of doxazosin, and has the advantages of simple conditions, few side reactions, easy separation and purification, and high yield With the advantages of high and high stereoselectivity, bimatoprost can be obtained simply and efficiently.

Description

technical field [0001] The invention relates to the field of chemical synthesis, in particular to a synthesis method of bimatoprost. Background technique [0002] Glaucoma is the second most common cause of blindness and the leading cause of irreversible blindness in the world. Glaucoma is a group of diseases characterized by optic disc atrophy and depression, visual field defect and vision loss. Pathological increased intraocular pressure and optic nerve insufficiency are the primary risk factors for its onset. The tolerance of optic nerve to pressure damage is also related to The occurrence and development of glaucoma. Obstacles in any part of the aqueous humor circulation pathway can lead to pathological changes caused by elevated intraocular pressure, but some patients also present with normal intraocular pressure glaucoma. Glaucoma is one of the three major blindness diseases that cause blindness in humans, with an incidence rate of 1% in the general population and 2%...

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 Patents(China)
IPC IPC(8): C07C405/00
CPCC07C405/0041C07C2601/08C07B2200/07
Inventor 李铁旦李扬
Owner GUANGZHOU KEMROCMED CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products