CN107778228A - A kind of exquisite method of Menglusitena - Google Patents
A kind of exquisite method of Menglusitena Download PDFInfo
- Publication number
- CN107778228A CN107778228A CN201610719454.3A CN201610719454A CN107778228A CN 107778228 A CN107778228 A CN 107778228A CN 201610719454 A CN201610719454 A CN 201610719454A CN 107778228 A CN107778228 A CN 107778228A
- Authority
- CN
- China
- Prior art keywords
- menglusitena
- ethanol
- crude product
- mixed liquor
- sodium crystal
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
- C07D215/18—Halogen atoms or nitro radicals
Abstract
The invention belongs to medicinal chemistry arts, it is related to a kind of exquisite method of Menglusitena, by Menglusitena crude product alcohols and the mixed liquor of ethyl acetate, stirring and crystallizing；It is collected by filtration, washs, the montelukast sodium crystal for being dried in vacuo pure, yield more than 90%, purity（HPLC）Up to 99.4%, impurity is set to be reduced to 0.1% or so.
Description
Technical field
The invention belongs to medicinal chemistry arts, and in particular to a kind of exquisite method of Menglusitena.
Background technology
Menglusitena（Montelukast sodium）It is a new generation's selection that United States Merck company is researched and developed for many years
Property LTRA, be the optimal drug for treating asthma and allergic rhinitis in the world at present, protected so far from listing
Hold annual more than 10% sale amplification.
The entire industries that United States Merck company discloses Menglusitena in the patent of Publication No. 1139429 are combined to
Method, the preparation method of Menglusitena is also disclosed that in the prior art, recorded in wherein CN104119270A and used oil
The crude product that ether, normal hexane or normal heptane carry out Menglusitena carries out exquisiteness.
Research of the present inventor by Menglusitena crude product exquisiteness method in the prior art, finds in the prior art
The method of record still suffers from that operating procedure is extremely complex, product purity is low, and impurity content is high, the problems such as yield is low, therefore this is just
There is an urgent need to a kind of good exquisite method to carry out exquisite Menglusitena.
The content of the invention
Higher for impurity content present in prior art, the present invention provides a kind of exquisite method of Menglusitena,
Can effectively improve yield, reduce impurity content, unexpected effect is achieved using the present invention program, yield 90% with
On, it is 0.1% or so to make impurity content.
The present invention is achieved through the following technical solutions, and is comprised the following steps：
(1) by the mixed liquor that Menglusitena crude product adds alcohols and ethyl acetate volume ratio is 1: 1~4, heating stirring, analysis
It is brilliant；
（2）The montelukast sodium crystal of precipitation is collected by filtration, is washed with ethanol water, the montelukast for being dried in vacuo pure
Sodium crystal.
Step（1）Middle preferred alcohols are one or more kinds of mixing in ethanol, normal propyl alcohol, isopropanol and n-butanol
Liquid；Menglusitena: mixed liquor=1g: 200~250ml of alcohols and ethyl acetate, preferably 15 DEG C~25 DEG C of recrystallization temperature.Analysis
The brilliant time between 1h~10h, preferably 2h~6h.
Vacuum drying temperature is 30~40 DEG C in step (2), and vacuum is -0.09~-0.1MPa, drying time 20~30
Hour.
Ethanol water dosage is 15-25 times of Menglusitena crude product in step (2), and the volume ratio of ethanol and pure water
For 1: 3~5.
The technique effect of the present invention：The present invention is simple to operate, and yield, purity are high, can be effectively reduced the content of impurity, miscellaneous
Matter content is 0.1% or so.
Embodiment
Now beneficial effects of the present invention are further described by following examples, it is thus understood that these embodiments are only used for
The purpose of illustration, is not limited the scope of the invention, at the same those of ordinary skill in the art according to the present invention done it is apparent
Change and modification be also contained within the scope of the invention.
Embodiment 1
(1) Menglusitena crude product 5.0g is put into single port bottle, adds 1000ml ethanol, ethyl acetate mixtures (ethanol: second
Acetoacetic ester=1: 2.5), under conditions of 45 DEG C, stirring and dissolving, temperature was in 20 DEG C of stirring and crystallizings 2 hours；
(2) the montelukast sodium crystal of precipitation is collected by filtration, with 80ml ethanol pure water solution (ethanol: pure water=1: 3) mixed liquor
Washing, dried in the baking oven under the conditions of 30 DEG C, obtain 4.5g montelukast sodium crystals, yield 90%, purity (HPLC)
99.2%.
Embodiment 2
(1) Menglusitena crude product 5.0g is put into single port bottle, adds 1250ml ethanol, ethyl acetate mixtures (ethanol: second
Acetoacetic ester=1: 1), under conditions of 40 DEG C, stirring and dissolving, in 25 DEG C of stirring and crystallizings 4 hours；
(2) the montelukast sodium crystal of precipitation is collected by filtration, with 100ml ethanol pure water solution (ethanol: pure water=1: 4) mixed liquor
Wash and dried in the baking oven under the conditions of 30 DEG C, obtain 4.6g montelukast sodium crystals, yield 92%, purity (HPLC)
99.4%.
Embodiment 3
(1) Menglusitena crude product 5.0g is put into single port bottle, adds 1000ml isopropanols, ethyl acetate mixtures (isopropyl
Alcohol: ethyl acetate=1: 3), and under conditions of 35 DEG C, stirring and dissolving, in 30 DEG C of stirring and crystallizings 5 hours；
2) the montelukast sodium crystal of precipitation is collected by filtration, with 120ml ethanol pure water solution (ethanol: pure water=1: 5) mixed liquor
Wash and dried in the baking oven under the conditions of 30 DEG C, obtain 4.55g montelukast sodium crystals, yield 91%, purity (HPLC)
99.2%.
Claims (5)
1. a kind of exquisite method of Menglusitena, comprises the following steps：
（1）It is 1 that Menglusitena crude product is added into alcohols and ethyl acetate volume ratio:1~4 mixed liquor, heating stirring, analysis
It is brilliant；
（2）The montelukast sodium crystal of precipitation is collected by filtration, is washed with ethanol water, the montelukast for being dried in vacuo pure
Sodium crystal.
2. method according to claim 1, it is characterised in that step（1）Middle alcohol is ethanol, normal propyl alcohol one or more
Mixed liquor.
3. method according to claim 1, it is characterised in that step（1）Middle recrystallization temperature is 15~25 DEG C, and the crystallization time is 2
~6 hours.
4. method according to claim 1, it is characterised in that step（2）Middle ethanol water dosage is Menglusitena crude product
15-25 times, and the volume ratio of ethanol and pure water be 1:3~5.
5. method according to claim 1, it is characterised in that step（2）Drying temperature is 30~40 DEG C, drying time 20
~30 hours.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610719454.3A CN107778228A (en) | 2016-08-25 | 2016-08-25 | A kind of exquisite method of Menglusitena |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610719454.3A CN107778228A (en) | 2016-08-25 | 2016-08-25 | A kind of exquisite method of Menglusitena |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107778228A true CN107778228A (en) | 2018-03-09 |
Family
ID=61393544
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610719454.3A Pending CN107778228A (en) | 2016-08-25 | 2016-08-25 | A kind of exquisite method of Menglusitena |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107778228A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107162969A (en) * | 2017-07-05 | 2017-09-15 | 成都亿知科技有限公司 | Montelukast sodium crystal and preparation method thereof and pharmaceutical composition |
-
2016
- 2016-08-25 CN CN201610719454.3A patent/CN107778228A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107162969A (en) * | 2017-07-05 | 2017-09-15 | 成都亿知科技有限公司 | Montelukast sodium crystal and preparation method thereof and pharmaceutical composition |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20180309 |