CN103664753A - Method for preparing atazanavir disulfate A-type crystal - Google Patents
Method for preparing atazanavir disulfate A-type crystal Download PDFInfo
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- CN103664753A CN103664753A CN201210324747.3A CN201210324747A CN103664753A CN 103664753 A CN103664753 A CN 103664753A CN 201210324747 A CN201210324747 A CN 201210324747A CN 103664753 A CN103664753 A CN 103664753A
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- free alkali
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/42—Radicals substituted by singly-bound nitrogen atoms having hetero atoms attached to the substituent nitrogen atom
Abstract
The invention discloses a novel method for preparing atazanavir disulfate A-type crystal. The method particularly comprises the following steps: dissolving atazanavir free alkali into an organic solvent, and then adding concentrated sulfuric acid to a solution, and devitrifying, so as to obtain the A-type crystal of the atazanavir disulfate. The method disclosed by the invention is simple and convenient to operate, high in yield, and applicable to industrial production.
Description
Technical field
The invention belongs to pharmaceutical chemistry technical field, be specifically related to the preparation method of the A type crystallization of Zrivada.
Background technology
Reyataz R is a kind of azepine peptide hiv protease inhibitor, and inhibition HIV-1 virus to height is active.Its chemical name is (3S, 8S, 9S, 12S)-3, two (1,1-dimethyl ethyl)-8-hydroxyl-4-11-dioxo-9-(phenmethyl)-6-[[4-(2-the pyridyl)-phenmethyls of 12-]-2,5,6,10,13-pentaaza tetradecanedioic acid dimethyl ester, structural formula is as follows:
WO9936404 discloses the crystalline bisulfate of Reyataz R, and it has the oral administration biaavailability that specific ionization alkali obviously improves in animal body, and has solubleness and stability in better water than other salt.
WO9936404 discloses I type (being called as afterwards A type) and the crystallization of II type of Zrivada, and wherein I type is anhydrous, non-solvent compound crystal formation, and II type is water absorbability hydrate crystal forms.WO2005108349 discloses C type and the crystallization of E3 type of Zrivada, and C type is hydrate crystal forms, and E3 type is the solvate crystal formation containing 3 molecules of ethanol.
In addition, WO2010079497 discloses the H1 N-type waferN of Zrivada; WO2011027324 discloses Type B, P type and the amorphous of Zrivada.
Medicinal crystal-form is in the market the crystallization of A type.WO9936404 discloses the method for a kind of A of preparation type crystallization: at 50 ℃, the sulfuric acid of 5M is added drop-wise in the acetone suspension of Zrivada, adds Reyataz R free alkali crystal seed crystallization, obtain the crystallization of Zrivada A type.
WO2005108349 has done improvement to this method: Reyataz R free alkali is dissolved in the mixed solvent of acetone and N-Methyl pyrrolidone, the vitriol oil of first add-on for reacting with the Reyataz R free alkali that is less than 15% weight, the crystal seed that adds again A N-type waferN, then by cubic equation, with the speed increasing, divide 5 stages to add the remaining vitriol oil, progressively crystallization.The crystal size obtaining is by this method even, but extremely loaded down with trivial details in the method operation, and has used N-Methyl pyrrolidone as solvent, and the dissolvent residual limit that N-Methyl pyrrolidone requires in pharmacopeia is very low, and quality product is not easy up to standard.
To sum up, this area, method of preparing Zrivada A type crystallization of being efficiently applicable to suitability for industrialized production easy in the urgent need to developing.
Summary of the invention
The object of the invention is just to provide a kind of new method of preparing simply, efficiently the crystallization of Zrivada A type.
The preparation method who the invention provides the crystallization of a kind of Zrivada A type, is characterized in that, comprises the steps:
1) mixed system that provides Reyataz R free alkali to mix with organic solvent, wherein, described organic solvent is selected from lower group: DMSO, DMF or containing the mixed solvent of DMSO and/or DMF, wherein said mixed solvent consists of with one or more solvents that are selected from (ii) group one or more solvents that are selected from (i) group
(i) group solvent is: DMSO and DMF;
(ii) group solvent is: acetone, ether solvent and esters solvent;
2) in above-mentioned system, add the vitriol oil;
3) crystallize out from described system, obtains the crystallization of Zrivada A type.
In another preference, described mixed solvent is selected from lower group: the mixed solvent of the mixed solvent of mixed solvent, DMF and the ethers of the mixed solvent of the mixed solvent of the mixed solvent of acetone and DMSO, acetone and DMF, acetone/DMSO/DMF three's mixed solvent, DMSO and ethers, DMSO and ester class, DMF and ester class, DMSO/DMF/ ethers three's mixed solvent or DMSO/DMF/ ester class three's mixed solvent.
Preferably, described ether solvent is selected from lower group: ether, propylene oxide, tetrahydrofuran (THF), dioxane, glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, or its combination; And/or
Described esters solvent is selected from lower group: ritalin, vinyl acetic monomer, propyl acetate, N-BUTYL ACETATE, or its combination.
In another preference, in mixed solvent, the consumption of each solvent can be all 1～100 weight part, is preferably 1～30 weight part.
Preferably, the weight ratio of described solvent or volume ratio are 1～100:100～1, preferably 1～50:50～1, more preferably 1～30:30～1.
In another preference, described solvent is acetone/DMSO mixed solvent that weight ratio or volume ratio are 1～20:20～1.
In another preference, step 1) in, the envelope-bulk to weight ratio of organic solvent and Reyataz R free alkali is 1～100ml:1g, is preferably 1～50ml:1g, more preferably, the envelope-bulk to weight ratio of organic solvent and Reyataz R free alkali is 1～20ml:1g.
In another preference, step 2) in, the mol ratio of the vitriol oil and Reyataz R free alkali is 0.1～2:1, is preferably 0.5～1.8:1, more preferably 0.9～1.5:1.
In another preference, before crystallize out process or among add crystal seed, preferably add Reyataz R A N-type waferN as crystal seed.
In another preference, the charging capacity of described crystal seed and Reyataz R free alkali mass ratio are: 0.1～30:100, is preferably 0.5～20:100.
In another preference, described method also has one or more following characteristics:
(a) in step (1), at 25～60 ℃, (preferably 30～50 ℃), are dissolved in organic solvent by Reyataz R free alkali, form solution;
(b), in step (2), at 20～70 ℃, (preferably 35～50 ℃), add the vitriol oil;
(c), in step (3), at 20～80 ℃, (preferably 45～60 ℃), add crystal seed;
(d), in step (3), the crystallize out time is 8～10 hours;
(e) in step (3), at-20～30 ℃ (preferably-10～20 ℃), crystallize out from described solution;
(f) in step (3), also comprise the solution after crystallize out is filtered, thereby separation obtains the crystallization of Zrivada A type.
In another preference, step 1) in, described Reyataz R free alkali is dissolved in the solution of organic solvent, is the solution through filtration treatment and/or decolouring processing.
In another preference, it is activated carbon decolorizing that described decolouring is processed.
In another preference, when described decolouring is processed, the consumption of gac is 1% of Reyataz R free alkali weight.
In another preference, the volumetric molar concentration of the described vitriol oil is 15～18.4mol/L.
In should be understood that within the scope of the present invention, above-mentioned each technical characterictic of the present invention and can combining mutually between specifically described each technical characterictic in below (eg embodiment), thus form new or preferred technical scheme.As space is limited, at this, tire out and state no longer one by one.
Accompanying drawing explanation
Fig. 1 is the XRD figure spectrum of Zrivada A type of the present invention crystallization;
Fig. 2 is the DSC collection of illustrative plates of Zrivada A type of the present invention crystallization;
Fig. 3 is the IR collection of illustrative plates of Zrivada A type of the present invention crystallization.
Embodiment
The inventor, through extensive and deep research, is surprised to find that, by selecting suitable organic solvent, and under certain temperature and PH condition, can be easy and prepare efficiently Reyataz R A N-type waferN, be applicable to suitability for industrialized production.In addition, the Zrivada A type crystallization that the present invention makes, its foreign matter content is low, and chemical purity is high, has good pharmaceutical characteristic, can be used as suppressing the activeconstituents of hiv protease medicine.
Term
As used in the present invention, term " Reyataz R free alkali " or " Reyataz R " are used interchangeably, and refer to compound (3S, 8S, 9S, 12S)-3, two (1,1-dimethyl ethyl)-8-hydroxyl-4-11-dioxo-9-(phenmethyl)-6-[4-(2-the pyridyl)-phenmethyls of 12-]-2,5,6,10,13-pentaaza tetradecanedioic acid dimethyl ester.
Raw material Reyataz R free alkali can make with ordinary method (as the method being provided in patent WO9740029), also can obtain by purchase.
Sulfuric acid Reyataz R is the pharmaceutical salts of Reyataz R, and also referred to as the hydrosulfate of Reyataz R, its structural formula is as follows:
Term " vitriol oil " refers generally to the sulfuric acid that sulfuric acid mass percent is more than 80% (preferably more than 90%, more preferably more than 95%, best 98%).Conventionally, the volumetric molar concentration of the vitriol oil is 15-18.4mol/L.
Term " organic solvent " refers to or above-mentioned both mixed solvents independent or common and that acetone according to arbitrary volume ratio combine independent by DMSO, DMF substantially.Representational example comprises: the mixed solvent of the mixed solvent of acetone and DMSO, acetone and DMF, DMSO, DMF, or acetone, DMSO, DMF three's mixed solvent, or the mixed solvent of the mixed solvent of the mixed solvent of DMSO and ethers, DMSO and ester class or the mixed solvent of the mixed solvent of DMF and ethers, DMF and ester class and the mixed solvent of DMSO, DMF and ethers, DMSO, DMF and ester class.
Term " ether solvent " refers to have the straight or branched ether organic solvent of 2-20 individual (preferably 2-10) carbon atom, for example ether, propylene oxide, tetrahydrofuran (THF), dioxane, glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, or similar solvent.
Term " esters solvent " refers to have the ester class organic solvent of 2-20 (preferably 2-10) carbon atom, for example ritalin, vinyl acetic monomer, propyl acetate, N-BUTYL ACETATE, or similar solvent.
In addition, organic solvent of the present invention can contain a small amount of other solvents, does not contain N-Methyl pyrrolidone in preferred organic solvent.
The preparation of Zrivada A type crystallization
Conventionally, the preparation method of Zrivada A type crystallization comprises:
Reyataz R free alkali is dissolved in organic solvent;
Then, in above-mentioned solution, add the vitriol oil;
Stir, crystallize out, obtains the crystallization of Zrivada A type.
In the present invention, for the organic solvent that dissolves Reyataz R free alkali, be the mixed solvent of mixed solvent, acetone and DMF of DMSO, DMF, acetone and DMSO or acetone and DMSO, DMF three's mixed solvent, or the mixed solvent of the mixed solvent of the mixed solvent of DMSO and ethers, DMSO and ester class or the mixed solvent of the mixed solvent of DMF and ethers, DMF and ester class and the mixed solvent of DMSO, DMF and ethers, DMSO, DMF and ester class.
Preferably, described ether solvent is selected from lower group: ether, propylene oxide, tetrahydrofuran (THF), dioxane, glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether; Described esters solvent is selected from lower group: ritalin, vinyl acetic monomer, propyl acetate, N-BUTYL ACETATE.
Any component in above-mentioned mixed solvent all can combine according to arbitrary volume ratio.
Preferably, described for dissolving the mixed solvent that the organic solvent of Reyataz R free alkali is acetone and DMSO, be preferably acetone/DMSO mixed solvent of 1～20:20～1.
In the present invention, for dissolving the organic solvent of Reyataz R free alkali and the envelope-bulk to weight ratio of Reyataz R free alkali is 1～100ml:1g, preferably 1～50ml:1g, is preferably 1～20ml:1g.
In the present invention, the mol ratio of the vitriol oil and Reyataz R free alkali is 0.1～2:1, is preferably 0.5～1.8:1, more preferably 0.9～1.5:1.
Major advantage of the present invention comprises:
(a) preparation method of the present invention is easy and simple to handle.
(b) product yield is high, can reach 95% or higher, is applicable to suitability for industrialized production.
(c) Zrivada making by method of the present invention, epigranular, purity is high.The chemical purity that HPLC measures can reach 99.5% or higher, and single contaminant is all less than 0.1%, and all technical reaches pharmacopeia requirement.
Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiment are only not used in and limit the scope of the invention for the present invention is described.The experimental technique of unreceipted actual conditions in the following example, conventionally according to normal condition, the raw materials used Reyataz R free alkali of the present invention can prepare with reference to WO9740029.
Embodiment 1
150g Reyataz R free alkali (212.8mmol), 1000ml acetone, 150ml DMSO are joined in reaction flask, stir, be warming up to 45-50 ℃.After dissolution of solid, add 1.5g gac, insulation continues to stir 15-30 minute.
Filter, in filtrate, add the 13ml vitriol oil (239.2mmol), temperature is controlled at 45-50 ℃, adds the crystal seed of 1.5g Zrivada A N-type waferN, insulated and stirred 4-6 hour.Slow cooling to 10 ℃, continues insulated and stirred 4 hours.
Filter cold washing with acetone for filter cake.Drying under reduced pressure 2-3 hour under room temperature, then at 45-55 ℃ of drying under reduced pressure 2-3 hour, obtain Zrivada crystal 167g, molar yield 97.7%.It is 99.7% that HPLC detects chemical purity, and single contaminant is all less than 0.1%.
As shown in Figure 1, as shown in Figure 2, infrared spectra spectrogram as shown in Figure 3 for differential scanning spectrogram for the x-ray diffractogram of powder of the product crystal that the present embodiment makes.
Embodiment 2
15g Reyataz R free alkali (21.28mmol), 60ml DMSO are joined in reaction flask, stir, be warming up to 30-35 ℃.
After dissolution of solid, in solution, add the 1.6ml vitriol oil (29.44mmol), temperature is controlled at 45-50 ℃, adds the crystal seed of 0.1g Zrivada A N-type waferN, insulated and stirred 3-5 hour.Then slow cooling to 5 ℃, continues insulated and stirred 2 hours.
Filter cold washing with acetone for filter cake.45-55 ℃ of drying under reduced pressure 5-6 hour, obtains Zrivada crystal 16.3g, molar yield 95.4%.It is 99.8% that HPLC detects chemical purity, and single contaminant is all less than 0.1%.
As shown in Figure 1, as shown in Figure 2, infrared spectra spectrogram as shown in Figure 3 for differential scanning spectrogram for the x-ray diffractogram of powder of the product crystal that the present embodiment makes.
50g Reyataz R free alkali (70.94mmol), 500ml acetone, 30ml DMF are joined in reaction flask, stir, be warming up to 35-40 ℃.After dissolution of solid, filtered while hot.In filtrate, add 0.5g gac, insulation continues to stir 15-30 minute.
Filter, in filtrate, add the 4.7ml vitriol oil (86.48mmol), add, be warming up to 50-60 ℃, add the crystal seed of 0.5g Zrivada A N-type waferN, insulated and stirred 2-4 hour.Slow cooling to 0 ℃, continues insulated and stirred 3 hours.
Filter cold washing with acetone for filter cake.Drying under reduced pressure 2-3 hour under room temperature, then 45-55 ℃ of drying under reduced pressure 2-3 hour, obtain Zrivada crystal 54.8g, molar yield 96.2%.It is 99.5% that HPLC detects chemical purity, and single contaminant is all less than 0.1%.
As shown in Figure 1, as shown in Figure 2, infrared spectra spectrogram as shown in Figure 3 for differential scanning spectrogram for the x-ray diffractogram of powder of the product crystal that the present embodiment makes.
Embodiment 4
50g Reyataz R free alkali (70.94mmol), 750ml acetone, 30ml DMF are joined in reaction flask, stir, be warming up to 35-40 ℃.After dissolution of solid, filtered while hot.In filtrate, add 0.5g gac, insulation continues to stir 15-30 minute.
Filter, in filtrate, add the 4.0ml vitriol oil (73.60mmol), add, have crystal to separate out, be warming up to 50-60 ℃, insulated and stirred 2-4 hour.Slow cooling to 0 ℃, continues insulated and stirred 3 hours.
Filter cold washing with acetone for filter cake.Drying under reduced pressure 2-3 hour under room temperature, then 45-55 ℃ of drying under reduced pressure 2-3 hour, obtain Zrivada crystal 54.2g, molar yield 95.2%.It is 99.7% that HPLC detects chemical purity, and single contaminant is all less than 0.1%.
As shown in Figure 1, as shown in Figure 2, infrared spectra spectrogram as shown in Figure 3 for differential scanning spectrogram for the x-ray diffractogram of powder of the product crystal that the present embodiment makes.
Embodiment 5
150g Reyataz R free alkali (212.8mmol), 1200ml tetrahydrofuran (THF), 150ml DMSO are joined in reaction flask, stir, be warming up to 45-50 ℃.After dissolution of solid, add 1.5g gac, insulation continues to stir 15-30 minute.
Filter, in filtrate, add the 13ml vitriol oil (239.2mmol), temperature is controlled at 45-50 ℃, adds the crystal seed of 1.5g Zrivada A N-type waferN, insulated and stirred 4-6 hour.Slow cooling to 10 ℃, continues insulated and stirred 4 hours.
Filter cold tetrahydrofuran (THF) washing for filter cake.Drying under reduced pressure 2-3 hour under room temperature, then at 45-55 ℃ of drying under reduced pressure 2-3 hour, obtain Zrivada crystal 165g, molar yield 96.6%.It is 99.6% that HPLC detects chemical purity, and single contaminant is all less than 0.1%.
As shown in Figure 1, as shown in Figure 2, infrared spectra spectrogram as shown in Figure 3 for differential scanning spectrogram for the x-ray diffractogram of powder of the product crystal that the present embodiment makes.
Embodiment 6
150g Reyataz R free alkali (212.8mmol), 1500ml vinyl acetic monomer, 100ml DMSO, 50ml DMF are joined in reaction flask, stir, be warming up to 45-50 ℃.After dissolution of solid, add 1.5g gac, insulation continues to stir 15-30 minute.
Filter, in filtrate, add the 13ml vitriol oil (239.2mmol), temperature is controlled at 45-50 ℃, adds the crystal seed of 1.5g Zrivada A N-type waferN, insulated and stirred 4-6 hour.Slow cooling to 10 ℃, continues insulated and stirred 4 hours.
Filter cold vinyl acetic monomer washing for filter cake.Drying under reduced pressure 2-3 hour under room temperature, then at 45-55 ℃ of drying under reduced pressure 2-3 hour, obtain Zrivada crystal 167.1g, molar yield 97.8%.It is 99.5% that HPLC detects chemical purity, and single contaminant is all less than 0.1%.
As shown in Figure 1, as shown in Figure 2, infrared spectra spectrogram as shown in Figure 3 for differential scanning spectrogram for the x-ray diffractogram of powder of the product crystal that the present embodiment makes.
The Zrivada crystallization of preparing for embodiment 1-6, confirms that through X-ray powder diffraction and dsc, infrared spectroscopy analysis gained crystal is the crystallization of A type.
All documents of mentioning in the present invention are all quoted as a reference in this application, just as each piece of document, are quoted as a reference separately.In addition should be understood that those skilled in the art can make various changes or modifications the present invention after having read above-mentioned teachings of the present invention, these equivalent form of values fall within the application's appended claims limited range equally.
Claims (10)
1. a preparation method for Zrivada A type crystallization, is characterized in that, comprises the steps:
1) mixed system that provides Reyataz R free alkali to mix with organic solvent, wherein, described organic solvent is selected from lower group: DMSO, DMF or containing the mixed solvent of DMSO and/or DMF, wherein said mixed solvent consists of with one or more solvents that are selected from (ii) group one or more solvents that are selected from (i) group
(i) group solvent is: DMSO and DMF;
(ii) group solvent is: acetone, ether solvent and esters solvent;
2) in above-mentioned system, add the vitriol oil;
3) crystallize out from described system, obtains the crystallization of Zrivada A type.
2. method according to claim 1, it is characterized in that, described ether solvent is selected from lower group: ether, propylene oxide, tetrahydrofuran (THF), dioxane, glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, or its combination; And/or
Described esters solvent is selected from lower group: ritalin, vinyl acetic monomer, propyl acetate, N-BUTYL ACETATE, or its combination.
3. method according to claim 1, is characterized in that, in mixed solvent, the consumption of each solvent can be all 1～100 weight part, is preferably 1～30 weight part.
4. method according to claim 1, is characterized in that step 1) in, the envelope-bulk to weight ratio of organic solvent and Reyataz R free alkali is 1～100ml:1g, be preferably 1～50ml:1g, more preferably, the envelope-bulk to weight ratio of organic solvent and Reyataz R free alkali is 1～20ml:1g.
5. method according to claim 1, is characterized in that step 2) in the mol ratio of the vitriol oil and Reyataz R free alkali be 0.1～2:1, be preferably 0.5～1.8:1, more preferably 0.9～1.5:1.
6. method according to claim 1, is characterized in that, before crystallize out process or among add crystal seed, preferably add Reyataz R A N-type waferN as crystal seed.
7. method according to claim 6, is characterized in that, the charging capacity of described crystal seed and Reyataz R free alkali mass ratio are: 0.1～30:100, is preferably 0.5～2:100.
8. method according to claim 1, is characterized in that, described method also has one or more following characteristics:
(a) in step (1), at 25～60 ℃, (preferably 30～50 ℃), are dissolved in organic solvent by Reyataz R free alkali, form solution;
(b), in step (2), at 20～70 ℃, (preferably 35～50 ℃), add the vitriol oil;
(c), in step (3), at 20～80 ℃, (preferably 45～60 ℃), add crystal seed;
(d), in step (3), the crystallize out time is 8～10 hours;
(e) in step (3), at-20～30 ℃ (preferably-10～20 ℃), crystallize out from described solution;
(f) in step (3), also comprise the solution after crystallize out is filtered, thereby separation obtains the crystallization of Zrivada A type.
9. according to method claimed in claim 1, it is characterized in that step 1) in, described Reyataz R free alkali is dissolved in the solution of organic solvent, is the solution through filtration treatment and/or decolouring processing.
10. method according to claim 1, is characterized in that, the volumetric molar concentration of the described vitriol oil is 15～18.4mol/L.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111349042A (en) * | 2018-12-20 | 2020-06-30 | 陕西理工大学 | Atazanavir single crystal and preparation method thereof |
| TWI791916B (en) * | 2018-10-31 | 2023-02-11 | 法商施維雅藥廠 | Novel salt of a bcl-2 inhibitor, related crystalline form, method for preparing the same and pharmaceutical compositions containing the same |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101565398A (en) * | 2004-05-04 | 2009-10-28 | 布里斯托尔-迈尔斯斯奎布公司 | Process for preparing atazanavir bisulfate and novel forms |
| WO2011027324A1 (en) * | 2009-09-03 | 2011-03-10 | Ranbaxy Laboratories Limited | Polymorphic forms of atazanavir sulfate |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101565398A (en) * | 2004-05-04 | 2009-10-28 | 布里斯托尔-迈尔斯斯奎布公司 | Process for preparing atazanavir bisulfate and novel forms |
| WO2011027324A1 (en) * | 2009-09-03 | 2011-03-10 | Ranbaxy Laboratories Limited | Polymorphic forms of atazanavir sulfate |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI791916B (en) * | 2018-10-31 | 2023-02-11 | 法商施維雅藥廠 | Novel salt of a bcl-2 inhibitor, related crystalline form, method for preparing the same and pharmaceutical compositions containing the same |
| CN111349042A (en) * | 2018-12-20 | 2020-06-30 | 陕西理工大学 | Atazanavir single crystal and preparation method thereof |
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