CN108069914A - A kind of preparation method of West pa lattice crystal form - Google Patents
A kind of preparation method of West pa lattice crystal form Download PDFInfo
- Publication number
- CN108069914A CN108069914A CN201611013340.3A CN201611013340A CN108069914A CN 108069914 A CN108069914 A CN 108069914A CN 201611013340 A CN201611013340 A CN 201611013340A CN 108069914 A CN108069914 A CN 108069914A
- Authority
- CN
- China
- Prior art keywords
- west
- lattice
- preparation
- crystal form
- 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.)
- Withdrawn
Links
Classifications
-
- 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
- C07D241/20—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
It is a primary object of the present invention to provide a kind of preparation method of West pa lattice crystal form, using the crystal of this method preparation, X ray powder diffraction patterns exist（2θ±0.2°）9.3 °, 9.7 °, 16.8 °, 20.6 ° and 23.5 ° have characteristic peak, the method is easy to operate, it is molten it is residual less, product quality is stable, is suitble to the advantages that industrialized production.
Description
Technical field
The invention belongs to field of medicaments, and the present invention relates to the preparation methods of West pa lattice crystal form.
Background technology
In the claim 5 of world patent WO2002088084, the chemical formula of West pa lattice is disclosed, is 2- [4- [N-
(5,6- diphenyl pyrazine -2- bases)-N- isopropylaminos] butoxy }-N- (mesyl) acetamide, chemical abstracts accession number
CAS is 475086-01-2, also referred to as NS-304, and West pa lattice are with excellent PGI2 receptor agonisms, show bleeding
Platelet aggregation inhibitory action, vasorelaxation action, bronchus flesh dilating effect, lipidosis inhibitory action, white blood cell activation suppression
Make the various drug effects such as use, the structure such as formula of West pa lattice（1）It is shown：
Formula（1）
Three kinds of crystal forms of West pa lattice are disclosed in Chinese patent CN201080028176.8 patents, are respectively crystal form I, brilliant
Type II and crystal form III.Corresponding preparation method is also referred in the patent, and the solvent for preparing crystal form III is n-butyl acetate, second
The high boiling esters solvent such as isoamyl valerate, n-amyl acetate, solvent easily remain, and influence product quality, therefore prepare crystal form III
When the recrystallisation solvent that it is necessary to consider other low boiling points, easily remove.
The content of the invention
The invention belongs to field of medicaments, and in particular to a kind of preparation method of West pa lattice crystal form, the method are easy to operate, molten
It is residual less, product quality is stable, is suitble to the advantages that industrialized production.The use of high boiling solvent is easily residual in it there is now technology
It stays, difficult removing, in order to remove residual solvent, it may be necessary to raise baking material temperature or extend the baking material time, these operations all may
A series of serious influences are generated on the quality of product, in order to avoid using shadow of the higher boiling recrystallisation solvent to West pa lattice quality
It rings, the present invention provides a kind of rational excellent method for crystallising.
The present invention provides a kind of preparation method of West pa lattice crystal form, including：By the West pa lattice of arbitrary solid form
It dissolves by heating in ethyl acetate, isopropyl acetate, methyl acetate or its combination, room temperature is cooled to after dissolved clarification, in temperature-fall period
White solid is gradually precipitated, most after continuing stirring and crystallizing, the X-ray powder diffraction figure of gained crystal in fixed temperature range
It is in 2 θ（2θ±0.2°）9.3 °, 9.7 °, 16.8 °, 20.6 ° and 23.5 ° have characteristic peak.
Description of the drawings：
Fig. 1 is the X-ray powder diffraction collection for the West pa lattice crystal that ethyl acetate is obtained as recrystallisation solvent.
Specific embodiment
In order to which those skilled in the art is made to be better understood from technical scheme, it is non-that some are disclosed further below
Limiting embodiment, the present invention is described in further detail.
Pa lattice in West used in the present invention are prepared by method disclosed in WO2002088084.
Embodiment 1：The preparation of West pa lattice crystal form
5g Wests pa lattice and 40ml ethyl acetate are added in reaction bulb and are persistently stirred, are placed in solution under 75 DEG C ~ 80 DEG C environment
Gradual dissolved clarification is cooled to room temperature crystallization after dissolved clarification, a large amount of white solids is precipitated in reaction bulb, is transferred under -5 DEG C ~ 5 DEG C environment and protects
Temperature stirring 2h, is obtained by filtration solid, and in 40 DEG C of forced air drying 4h, ethyl acetate residual is that 0.086%, HPLC purity is 99.94%,
Its X-ray powder diffraction figure is as shown in Figure 1：
Characteristic peak is as follows：
| 2θ(°) | D- spacing（Å） | Intensity（%） |
| 4.589 | 19.239 | 23.5 |
| 9.25 | 9.553 | 37.0 |
| 9.593 | 9.213 | 100.0 |
| 15.777 | 5.612 | 21.2 |
| 16.728 | 5.295 | 48.5 |
| 17.131 | 5.172 | 33.4 |
| 17.794 | 4.981 | 29.6 |
| 19.577 | 4.531 | 36.5 |
| 20.032 | 4.429 | 30.3 |
| 20.508 | 4.327 | 55.8 |
| 21.555 | 4.119 | 21.1 |
| 22.657 | 3.921 | 20.9 |
| 23.432 | 3.793 | 41.8 |
| 24.150 | 3.682 | 17.8 |
| 25.040 | 3.553 | 27.3 |
Claims (4)
1. a kind of preparation method of West pa lattice crystal form, including：Any form of West pa lattice are dissolved by heating in low boiling point
In 100 DEG C of esters solvent, cool down crystallization, and the X-ray powder diffraction figure of gained crystal exists（2θ±0.2°）9.3°、9.7°、
16.8 °, 20.6 ° and 23.5 ° have characteristic peak.
2. the esters solvent of the method as described in claim 1, the wherein boiling point less than 100 DEG C is ethyl acetate, isopropyl acetate
Ester, methyl acetate or its combination.
3. the method as described in claim 1, wherein cooling Devitrification step induces crystallization for direct crystallization or crystal seed.
4. the method as described in claim 1, wherein the temperature in the heating for dissolving step is 20 DEG C ~ 100 DEG C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611013340.3A CN108069914A (en) | 2016-11-17 | 2016-11-17 | A kind of preparation method of West pa lattice crystal form |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611013340.3A CN108069914A (en) | 2016-11-17 | 2016-11-17 | A kind of preparation method of West pa lattice crystal form |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108069914A true CN108069914A (en) | 2018-05-25 |
Family
ID=62159948
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201611013340.3A Withdrawn CN108069914A (en) | 2016-11-17 | 2016-11-17 | A kind of preparation method of West pa lattice crystal form |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108069914A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021023271A1 (en) * | 2019-08-06 | 2021-02-11 | 南京明德新药研发有限公司 | Crystal form of compound as prostacyclin receptor agonist and preparation method therefor |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102459198A (en) * | 2009-06-26 | 2012-05-16 | 日本新药株式会社 | Crystals |
| JP2015134732A (en) * | 2014-01-17 | 2015-07-27 | 国立大学法人大阪大学 | Inhibitor for enhanced vascular permeability |
| CN105949135A (en) * | 2016-05-10 | 2016-09-21 | 湖南欧亚生物有限公司 | Synthetic method of selexipag |
| CN106008364A (en) * | 2016-05-26 | 2016-10-12 | 河北科技大学 | Preparation method of selexipag |
-
2016
- 2016-11-17 CN CN201611013340.3A patent/CN108069914A/en not_active Withdrawn
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102459198A (en) * | 2009-06-26 | 2012-05-16 | 日本新药株式会社 | Crystals |
| JP2015134732A (en) * | 2014-01-17 | 2015-07-27 | 国立大学法人大阪大学 | Inhibitor for enhanced vascular permeability |
| CN105949135A (en) * | 2016-05-10 | 2016-09-21 | 湖南欧亚生物有限公司 | Synthetic method of selexipag |
| CN106008364A (en) * | 2016-05-26 | 2016-10-12 | 河北科技大学 | Preparation method of selexipag |
Non-Patent Citations (1)
| Title |
|---|
| 赵临襄主编: "《化学制药工艺学》", 31 August 2015, 中国医药科技出版社 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021023271A1 (en) * | 2019-08-06 | 2021-02-11 | 南京明德新药研发有限公司 | Crystal form of compound as prostacyclin receptor agonist and preparation method therefor |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9416097B2 (en) | Crystalline minocycline base and processes for its preparation | |
| CN106256824B (en) | Preparation method of high-purity delafloxacin meglumine salt | |
| KR20150036336A (en) | Crystalline form i of tyrosine kinase inhibitor dimaleate and preparation methods thereof | |
| WO2017096772A1 (en) | Method for preparing anti-heart-failure medicine lcz696 | |
| JP2008531477A (en) | Organic compounds | |
| WO2016107289A1 (en) | Method for preparing sofosbuvir crystal form-6 | |
| CN108069914A (en) | A kind of preparation method of West pa lattice crystal form | |
| WO2022078122A1 (en) | New crystal forms of acalabrutinib and preparation method therefor | |
| CN109836382B (en) | Preparation method of cabozantinib malate and intermediate thereof | |
| CN102850418B (en) | A kind of crystallization and drying means preparing high purity azacitidine | |
| CN101962367B (en) | Method for purifying bendamustine hydrochloride | |
| CN104098548A (en) | Delafloxacin purifying method | |
| JP5827684B2 (en) | Method for preparing crystalline form A of 2- [3-cyano-4- (2-i-butoxy) phenyl] -4-methyl-5-thiazole-carboxylic acid (febuxostat) | |
| EP2412373A1 (en) | Method for preparing acyclovir 2/3 hydrate | |
| CN108947984B (en) | Preparation method of pranlukast | |
| CN113980012A (en) | Purification method of emtricitabine | |
| WO2016034150A1 (en) | Method for preparing bosutinib and crystal thereof | |
| CN109851627B (en) | Preparation method of cefuroxime sodium crystal compound | |
| CN106632347B (en) | Preparation method of pyrrolopyrazine compound and salt thereof | |
| CN104230799A (en) | Method for preparing aripiprazole crystal | |
| CN108658952B (en) | Preparation method of vilazodone hydrochloride IV crystal | |
| CN102731469B (en) | Preparation method of high-purity 1,4-dioxane-2-one | |
| CN112939858B (en) | Process for separating quinmerac and its isomer | |
| WO2015151190A1 (en) | Method for producing irsogladine maleate | |
| WO2015180582A1 (en) | New crystalline form of aripiprazole hemiethanolate, preparation method and use thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20180525 |
|
| WW01 | Invention patent application withdrawn after publication |