CN109553582A - Pyrrole glug thunder Natrium metabolism object and preparation method thereof - Google Patents
Pyrrole glug thunder Natrium metabolism object and preparation method thereof Download PDFInfo
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- CN109553582A CN109553582A CN201811552381.9A CN201811552381A CN109553582A CN 109553582 A CN109553582 A CN 109553582A CN 201811552381 A CN201811552381 A CN 201811552381A CN 109553582 A CN109553582 A CN 109553582A
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- pyrrole
- natrium
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- glug
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D241/18—Oxygen or sulfur atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to pharmaceutical synthesis fields, and in particular to a kind of pyrrole glug thunder Natrium metabolism object (I) and preparation method thereof.The invention of the another metabolite of pyrrole glug thunder sodium of the present invention provides a variety of methods and foundation for metabolism research in pyrrole glug thunder sodium clinical medicine body, and the metabolite is prepared can study for metabolism and provide control sample.
Description
Technical field
The present invention relates to pharmaceutical synthesis fields, and in particular to a kind of pyrrole glug thunder Natrium metabolism object and preparation method thereof.
Background technique
Pyrrole glug thunder sodium (Pyragrel Sodium), entitled (E) -3- { 3- methoxyl group -4- [(3,5, the 6- trimethyls of chemistry
Pyrazine -2- base) methoxyl group] phenyl } sodium acrylate, structural formula is as follows:
This drug is thromboxane synthetase inhibitor of new generation, is clinically used for treatment thrombotic disease, including acute
Ischemic cerebral is waited indefinitely, and II stage phase of clinical research is now in.During I phase clinical research, the body metabolism of drug is studied
It has been shown that, there are two metabolites: compound V, VI, concrete structure formula are as follows:
The preparations of these metabolins and structural identification for further clarify the metabolic condition of the drug in vivo provide according to
According to, and lay a good foundation for clinical work.
Have no the report of other metabolites.
Summary of the invention
The invention discloses the another metabolite of pyrrole glug thunder sodium in vivo, chemical names: (E) -3- { 3- methoxyl group -4-
[(6- methylol -3,5- dimethyl pyrazine -2- base) methoxyl group] phenyl } acrylic acid, structural formula is as follows:
The compound of the present invention (I) can be used to lower section method preparation:
The invention of the new metabolite of pyrrole glug thunder sodium of the present invention is that metabolism research mentions in pyrrole glug thunder sodium clinical medicine body
New method and foundation are supplied, the metabolite, which is prepared, can provide control sample for metabolism research.
Specific embodiment
Embodiment 1
The preparation of pyrrole glug thunder Natrium metabolism object (I):
(1) by 5g (E) -3- { 3- methoxyl group -4- [(3,5,6- trimethylpyrazine -2- base) methoxyl group] phenyl } acrylic acid second
Ester (compound II) and 4.82g m-chloro-benzoic acid peroxide are added in 100ml ethyl alcohol, 25~30 DEG C of temperature control, are stirred to react 8
Hour, 30% sodium thiosulfate is added and decomposes excessive m-chloro-benzoic acid peroxide, ethyl alcohol is concentrated out, it is molten with saturated sodium carbonate
In liquid and solution, then (100ml × 3 time) are extracted with dichloromethane, organic layer is dried, filtered with anhydrous magnesium sulfate, filtrate concentration
It is extremely dry to obtain 4.48g compound III, yield 85.82%.
(2) 4.45g compound III and 3.95g acetic anhydride is added in 50ml acetic acid, back flow reaction 6 hours, reaction solution
It is concentrated to dryness, obtains 5.5g compound IV, yield 71%.
(3) 5.5g compound IV is dissolved in 55ml ethyl alcohol, adds 55ml purified water and 0.57g sodium hydroxide, controlled
Temperature 55~60 DEG C, react 2 hours, ethyl alcohol is concentrated out, into concentrate be added 55ml purified water, with 1M salt acid for adjusting pH to 5~
6, it filters, with purifying water washing (10ml × 2 time), product is put into 70 ± 2 DEG C drying 6 hours in air dry oven, obtains 2.67g
Compound I crude product.Compound I crude product is added in 26ml ethyl alcohol, flow back dissolved clarification, it is cooled to 20~25 DEG C, crystallization 1 hour,
It filters, product is put into 70 ± 2 DEG C drying 4 hours in air dry oven, obtains 2.05g compound I, yield 51.15%. 1H
NMR (400MHz, DMSO) δ 12.20 (s, 1H), 7.53 (d, J=15.9Hz, 1H), 7.33 (d, J=1.5Hz, 1H), 7.21
(dd, J=8.3,1.6Hz, 1H), 7.13 (d, J=8.4Hz, 1H), 6.45 (d, J=15.9Hz, 1H), 5.22 (d, J=5.5
Hz, 3H), 4.59 (d, J=5.0Hz, 2H), 3.80 (s, 3H), 2.53 (s, 3H), 2.52 (s, 3H)
Claims (2)
1. the pyrrole glug thunder Natrium metabolism object of structure formula (I):
2. the preparation method of the pyrrole glug thunder Natrium metabolism object of claim 1, comprising:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811552381.9A CN109553582A (en) | 2018-12-19 | 2018-12-19 | Pyrrole glug thunder Natrium metabolism object and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811552381.9A CN109553582A (en) | 2018-12-19 | 2018-12-19 | Pyrrole glug thunder Natrium metabolism object and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109553582A true CN109553582A (en) | 2019-04-02 |
Family
ID=65870362
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811552381.9A Pending CN109553582A (en) | 2018-12-19 | 2018-12-19 | Pyrrole glug thunder Natrium metabolism object and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109553582A (en) |
-
2018
- 2018-12-19 CN CN201811552381.9A patent/CN109553582A/en active Pending
Non-Patent Citations (2)
| Title |
|---|
| GUOPING YANG，等: "Simultaneous determination of Pyragrel, a novel anti-thrombotic agent, and its two primary metabolites in plasma by HPLC–MS/MS", 《JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS》 * |
| 张强，等: "吡拉格雷钠的合成工艺", 《中国医药工业杂志》 * |
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| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
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| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20190402 |