Preparation method of dapoxetine impurity reference substance

A technology of impurity reference substance, dapoxetine, applied in the field of medicine

Pending Publication Date: 2021-12-31
南京卓康医药科技有限公司
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Its synthetic method has not been published yet

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 dapoxetine impurity reference substance
  • Preparation method of dapoxetine impurity reference substance
  • Preparation method of dapoxetine impurity reference substance

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0056] Example 1: Preparation of compound 7 using p-methoxychlorbenzyl

[0057]

[0058]Compound 3 (200g, 0.718mol, 1eq.) was dissolved in dichloromethane (2000ml), triethylamine (181.6g, 248.8ml, 1.795mol, 2.5eq.) was added, and the reaction solution was cooled to below 10°C, Add p-methoxychlorbenzyl (134.9g, 0.862mol, 1.2eq) dropwise, after the reaction is over, add 10% potassium bisulfate solution (1000ml), stir and separate layers, collect the lower organic phase, add n-heptane (1000ml) , cooled to 5±5°C for crystallization, filtered, and vacuum-dried at 40±5°C to obtain 260.4 g of an off-white solid with a yield of 91%, which is compound 7.

[0059] ESI-MS(+):399.2[M+H] + .1H-NMR (400MHz, CDCl3): 8.31(d, J=5.5Hz, 1H), 8.08(d, J=5.5Hz, 1H), 7.62~7.59(m, 3H), 7.40~7.27(m, 6H ),6.98(d,J=5.5Hz,2H),6.91(d,J=5.5Hz,2H),6.42(d,J=5.0Hz,1H),4.71(s,2H),4.43(t,J =7.0Hz, 1H), 3.92(t, J=7.5Hz, 2H), 3.70(s, 3H), 2.17(t, J=7.5Hz, 2H).

Embodiment 2

[0060] Embodiment 2: use p-methoxybromide to prepare compound 7

[0061]

[0062] Compound 3 (200g, 0.718mol, 1eq.) was dissolved in dichloromethane (2000ml), triethylamine (181.6g, 248.8ml, 1.795mol, 2.5eq.) was added, and the reaction solution was cooled to below 10°C, Add p-methoxybromide (173.3g, 0.862mol, 1.2eq) dropwise, after the reaction, add 10% potassium bisulfate solution (1000ml), stir and separate layers, collect the lower organic phase, add n-heptane (1000ml) , cooled to 5±5°C for crystallization, filtered, and vacuum-dried at 40±5°C to obtain 262.7 g of an off-white solid with a yield of 91.8%, which is compound 7.

Embodiment 3

[0063] Embodiment 3: preparation compound 8

[0064]

[0065] Compound 7 (50g, 0.125mol) was dissolved in nitrobenzene (300ml), aluminum chloride (33.46g, 0.25mol, 2eq.) was added, and compound 1 (42.31g, 0.251mol, 2eq.) was dissolved in Nitrobenzene (200ml), the reaction system was heated to 100-110°C, and the solution of compound 1 was added dropwise, and the dropwise addition took 3 hours, and the resulting reaction mixture was stirred and reacted at 100-110°C for 2 hours. Monitor the reaction (TLC monitoring condition is GF254 silica gel plate, developing agent is ethyl acetate:petroleum ether (v / v)=1:20, observe with 254nm ultraviolet light) until compound 7 basically disappears, stop heating, and cool to below 20°C .

[0066] The reaction solution was added dropwise to 10% dilute hydrochloric acid solution (1000ml), the lower organic phase was separated, washed with saturated sodium chloride solution (300ml×3), the organic phase was concentrated to dryness under redu...

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 a dapoxetine impurity reference substance, which comprises the following steps: (1) reacting 3-(naphthalene-1-yloxy)-1-phenylpropan-1-ol with a p-methoxybenzyl reagent to obtain a compound 7; (2) reacting the compound 7 with 3-chloro-1-phenylpropyl-1-ketone to obtain a compound 8; (3) removing a p-methoxybenzyl protecting group in the compound 8 by using an oxidizing agent to obtain a compound 4; (4) reacting the compound 4 with alkyl sulfonyl chloride, and then reacting the compound with dimethylamine to obtain the dapoxetine impurity reference substance as shown in a formula 6. The dapoxetine impurity reference substance shown in the formula 6 is prepared for the first time.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to a preparation method of a dapoxetine impurity reference substance. Background technique [0002] Dapoxetine is a selective serotonin reuptake inhibitor used for the treatment of premature ejaculation in men. Its structural formula is as follows, which may contain impurities (Formula 6). [0003] [0004] In the synthetic process of dapoxetine, a kind of preparation method of intermediate (formula 3) is to use 3-chloro-1-phenylpropan-1-one (formula 1) to obtain 3-chloro-1-benzene Propan-1-alcohol (Formula 2), followed by an ether-forming reaction with 1-naphthol, yields an intermediate (Formula 3). [0005] [0006] Wherein, in the process of being reduced to the intermediate (formula 2) from 3-chloro-1-phenylpropan-1-one (formula 1), there will be a small amount of 1 that is not reduced, and in the subsequent reaction with 1-naphthol During the reaction process, it wil...

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): C07C213/02C07C217/48
CPCC07C41/16C07C45/68C07C45/64C07C213/02C07C43/2055C07C49/84C07C217/48Y02P20/55
Inventor 李强刘子宁
Owner 南京卓康医药科技有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products