CN105622575A - Preparation method of Trelagliptin - Google Patents
Preparation method of Trelagliptin Download PDFInfo
- Publication number
- CN105622575A CN105622575A CN201610138121.1A CN201610138121A CN105622575A CN 105622575 A CN105622575 A CN 105622575A CN 201610138121 A CN201610138121 A CN 201610138121A CN 105622575 A CN105622575 A CN 105622575A
- Authority
- CN
- China
- Prior art keywords
- methyl
- lieting
- bent
- preparation
- reaction
- 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
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
Abstract
The invention belongs to the technical field of medicinal chemistry and particularly relates to a preparation method of Trelagliptin. The equation is shown in the specification. In the method, 2-(6-chloro-3-methyl-2,4-dioxo-3,4-dihydropyrimidine-1(2H)-methyl)-4-fluorobenzonitrile and (R)-3-aminopiperidine dihydrochloride are subjected to a normal-pressure reaction in a single organic solvent or a mixed solvent under the alkaline condition of an acid-binding agent, and then a Trelagliptin compound is obtained. By means of the method, a high-pressure reaction is avoided, and thus reaction safety is greatly enhanced. The reaction condition of the method is mild and easy to control, and the method can be applied to industrial production and preparation of Trelagliptin.
Description
Technical field
The invention belongs to field of pharmaceutical chemistry technology, it is specifically related to the preparation method of bent Ge Lieting.
Background technology
World Health Organization 2011 report point out that the whole world 3.5 hundred million people that have an appointment suffer from diabetes, it is reported, China just has more than 100,000,000 diabetic subjects.
Diabetes spp is in chronic metabolic disease, if control is not good, it is easy to produce the neural complication such as pathology, blood vessel pathology of diabetic nephropathy. Diabetic subject is it is generally required to Long-term taking medicine, and long-acting diabetes medicament has clear superiority in patient compliance etc., is a kind of trend of diabetes medicament. The diabetes medicament of the listing mainly biological medicament such as GLP-1 analogue Exenatide prolonged action preparation, Albiglutide of Per-Hop behavior can be realized at present, it is necessary to drug administration by injection.
DPP-IV inhibitor is a class Novel diabetes medicine, list and comprised sitagliptin, Vildagliptin, BMS-477118, Li Gelieting, Egelieting etc., wherein the sitagliptin annual sales amount of first listing is more than 4,000,000,000 dollars, other similar drugs not yet have outstanding behaviours due to homogeneity, and bent Ge Lieting is as the first small molecules diabetes medicament that can realize weekly administration, being expected in cut-throat competition has outstanding behaviours.
Bent Ge Lieting succinate is by a kind of novel DPP-IV inhibitors of Wu Tian company of Japan exploitation. On March 26th, 2015, the bent Ge Lieting succinate of Glucovance obtains the approval of health workfare portion of Japan, for the treatment of diabetes B.
Bent Ge Lieting (CAS 865759-25-7 at present; English name: Trelagliptin) preparation method mainly patent CN101374523A report method:
The method needs to use tube sealing reaction in the process of the bent Ge Lieting of preparation. Tube sealing reaction is the reaction of a kind of High Temperature High Pressure, amplifies and has very high danger, poor operability, and equipment requirements is very high, and cost is higher. In addition, under high-temperature and high-pressure conditions, side reaction is more, and impurity increases. And the method aftertreatment needs to use column chromatography or HPLC separation, and cost is very high, is unfavorable for scale operation. Therefore urgent needs exploitation is a kind of simple to operate, the production method that condition is relatively gentle, safe.
Summary of the invention
It is an object of the invention to provide the production method of a kind of simple to operate, safe bent Ge Lieting.
The concrete technical scheme of invention is: the preparation method of a kind of bent Ge Lieting, the present invention discloses the preparation method of bent Ge Lieting. Described method with the use of single organic solvent or the mixed solvent that mixes by single organic solvent and water, in atmospheric conditions, the bent Ge Lieting of preparation. This method avoid reaction under high pressure, significantly enhance the security of reaction. Described method reaction conditions is gentle, easy to control, can be used for the industrial production preparation of bent Ge Lieting.
A preparation method of bent Ge Lieting, reaction formula is as follows:
In single organic solvent or mixed solvent, by 2-(the chloro-3-methyl-2 of 6-, 4-bis-oxygen-3,4-dihydro-pyrimidin-1 (2H)-methyl)-4-fluorobenzonitrile and (R)-3-amino piperidine dihydrochloride, under the alkaline condition of acid binding agent, carry out synthesis under normal pressure, thus obtain bent Ge Lieting compound.
Above-mentioned single solvent is: tetrahydrofuran (THF), dioxane, methyl alcohol, ethanol, Virahol, the trimethyl carbinol, propyl carbinol, ethylene glycol, acetone or acetonitrile.
Above-mentioned mixed solvent is the mixed solvent mixed by above-mentioned single solvent and water.
Above-mentioned mixed solvent is the mixed solvent mixed by above-mentioned any 2 kinds of single solvents or single solvent of more than two kinds.
The mol ratio of the solvent of above-mentioned reaction and reagent 2-(6-chloro-3-methyl-2,4-two oxygen-3,4-dihydro-pyrimidin-1 (2H)-methyl)-4-fluorobenzonitrile (1) is greater than 5:1, it is preferable that ratio is 20-50:1.
Mentioned reagent 2-(6-chloro-3-methyl-2,4-two oxygen-3,4-dihydro-pyrimidin-1 (2H)-methyl)-4-fluorobenzonitrile (1) is 1:0.8-1.2:3-5 with the ratio of (R)-3-amino piperidine dihydrochloride (2) and acid binding agent.
Above-mentioned temperature of reaction is 50 degrees Celsius to 150 degrees Celsius, it is preferable that 60 degrees Celsius to 75 degrees Celsius.
The acid binding agent that aforesaid method uses is: sodium carbonate, salt of wormwood, sodium bicarbonate, saleratus, triethylamine or diisopropyl ethyl amine.
The reaction times of aforesaid method is 30 minutes to 24 hours, it is preferable that 2 is little of 5 hours.
Embodiment
Below by specific embodiment, the present invention is described:
Example 1.
Reaction flask adds 2-(the chloro-3-methyl-2 of 6-, 4-bis-oxygen-3,4-dihydro-pyrimidin-1 (2H)-methyl)-4-fluorobenzonitrile (2.930g, 0.010mol), dioxane (20ml), adds (R)-3-amino piperidine dihydrochloride (2.070g, 0.012mol) respectively under stirring, sodium bicarbonate (2.5g, 0.03mol). 75 degrees Celsius of stirring reactions 5 hours, LC-Ms detection reaction was complete, concentrating under reduced pressure. Crude product 20ml ethyl acetate backflow 1 hour, filtered while hot, filtrate hold over night, has solid to precipitate out, and filters and collects to obtain product.
Example 2.
Reaction flask adds 2-(the chloro-3-methyl-2 of 6-, 4-bis-oxygen-3,4-dihydro-pyrimidin-1 (2H)-methyl)-4-fluorobenzonitrile (29.3g, 0.1mol), dioxane (200ml), adds (R)-3-amino piperidine dihydrochloride (20.7g, 0.12mol) respectively under stirring, triethylamine (30.3g, 0.3mol). 70 degrees Celsius of stirring reactions 3 hours, LC-Ms detection reaction was complete, and reaction solution is cooled to room temperature, pours 500ml frozen water into, and 5-10 degree Celsius is stirred 2 hours, filters, and collects solid and obtains product.
Example 3
Reaction flask adds 2-(the chloro-3-methyl-2 of 6-, 4-bis-oxygen-3,4-dihydro-pyrimidin-1 (2H)-methyl)-4-fluorobenzonitrile (2.930g, 0.010mol), acetonitrile (15ml), adds (R)-3-amino piperidine dihydrochloride (2.07g, 0.012mol) respectively under stirring, salt of wormwood (4.14g, 0.03mol). 75 degrees Celsius of stirring reactions 5 hours, LC-Ms detection reaction was complete, and reaction solution is cooled to room temperature, pours 50ml frozen water into, and 5-10 degree Celsius is stirred 2 hours, filters, and collects solid and obtains product.
Example 4
Reaction flask adds 2-(the chloro-3-methyl-2 of 6-, 4-bis-oxygen-3,4-dihydro-pyrimidin-1 (2H)-methyl)-4-fluorobenzonitrile (29.3g, 0.1mol), the trimethyl carbinol (200ml), adds (R)-3-amino piperidine dihydrochloride (20.7g, 0.12mol) respectively under stirring, diisopropyl ethyl amine (30.3g, 0.3mol). 70 degrees Celsius of stirring reactions 3 hours, LC-Ms detection reaction was complete, and reaction solution is cooled to room temperature, pours 500ml frozen water into, and 5-10 degree Celsius is stirred 2 hours, filters, and collects solid and obtains product.
Example 5
Reaction flask adds 2-(the chloro-3-methyl-2 of 6-, 4-bis-oxygen-3,4-dihydro-pyrimidin-1 (2H)-methyl)-4-fluorobenzonitrile (29.3g, 0.1mol), tetrahydrofuran (THF) (150ml), deionized water (50ml), (R)-3-amino piperidine dihydrochloride (20.7g is added respectively under stirring, 0.12mol), sodium bicarbonate (25g, 0.3mol). 70 degrees Celsius of stirring reactions 4 hours, LC-Ms detection reaction was complete, and reaction solution is cooled to room temperature, separation upper organic phase, concentrated to obtain crude product. Product is obtained with ethyl acetate and sherwood oil recrystallization.
Example 6
Reaction flask adds 2-(the chloro-3-methyl-2 of 6-, 4-bis-oxygen-3,4-dihydro-pyrimidin-1 (2H)-methyl)-4-fluorobenzonitrile (29.3g, 0.1mol), dioxane (150ml), deionized water (50ml), (R)-3-amino piperidine dihydrochloride (20.7g is added respectively under stirring, 0.12mol), triethylamine (30.3g, 0.3mol). 70 degrees Celsius of stirring reactions 4.5 hours, LC-Ms detection reaction was complete, and reaction solution is cooled to room temperature, pours 600ml frozen water into, and 5-10 degree Celsius is stirred 2 hours, filters, and collects solid and obtains product.
Example 7
Reaction flask adds 2-(the chloro-3-methyl-2 of 6-, 4-bis-oxygen-3,4-dihydro-pyrimidin-1 (2H)-methyl)-4-fluorobenzonitrile (29.3g, 0.1mol), acetone (100ml), deionized water (50ml), (R)-3-amino piperidine dihydrochloride (20.7g is added respectively under stirring, 0.12mol), triethylamine (30.3g, 0.3mol). 80 degrees Celsius of stirring reactions 5 hours, LC-Ms detection reaction was complete, and reaction solution is cooled to room temperature, pours 500ml frozen water into, and 5-10 degree Celsius is stirred 2 hours, filters, and collects solid and obtains product.
Example 8
Reaction flask adds 2-(the chloro-3-methyl-2 of 6-, 4-bis-oxygen-3,4-dihydro-pyrimidin-1 (2H)-methyl)-4-fluorobenzonitrile (29.3g, 0.1mol), acetonitrile (100ml), deionized water (100ml), (R)-3-amino piperidine dihydrochloride (20.7g is added respectively under stirring, 0.12mol), diisopropyl ethyl amine (3.9g, 0.3mol). At 100 degrees Celsius of stirring reactions, 6 hours, LC-Ms detection reaction was complete, and reaction solution is cooled to room temperature, pours 500ml frozen water into, and 5-10 degree Celsius is stirred 2 hours, filters, and collects solid and obtains product.
Example 9
Reaction flask adds 2-cyano group-5-fluorobenzyl bromide (29.3g, 0.1mol), dioxane (100ml), deionized water (100ml), adds (R)-3-amino piperidine dihydrochloride (20.7g, 0.12mol) respectively under stirring, salt of wormwood (41.4g, 0.3mol). 80 degrees Celsius of stirring reactions 4 hours, LC-Ms detection reaction was complete, and reaction solution is cooled to room temperature, isolates upper organic phase, and concentrating under reduced pressure obtains crude product, obtains product by re-crystallizing in ethyl acetate.
Example 10
Reaction flask adds 2-(the chloro-3-methyl-2 of 6-, 4-bis-oxygen-3,4-dihydro-pyrimidin-1 (2H)-methyl)-4-fluorobenzonitrile (29.3g, 0.1mol), Virahol (200ml), adds (R)-3-amino piperidine dihydrochloride (20.7g, 0.12mol) respectively under stirring, diisopropyl ethyl amine (38.7g, 0.3mol). 70 degrees Celsius of stirring reactions 3 hours, LC-Ms detection reaction was complete, and reaction solution is cooled to room temperature, pours 500ml frozen water into, and 5-10 degree Celsius is stirred 2 hours, filters, and collects solid and obtains product.
Example 11
Reaction flask adds 2-(the chloro-3-methyl-2 of 6-, 4-bis-oxygen-3,4-dihydro-pyrimidin-1 (2H)-methyl)-4-fluorobenzonitrile (29.3g, 0.1mol), Virahol (200ml), deionized water (50ml) adds (R)-3-amino piperidine dihydrochloride (20.7g, 0.12mol) under stirring respectively, salt of wormwood (41.4g, 0.3mol). 70 degrees Celsius of stirring reactions 4 hours, LC-Ms detection reaction was complete, and reaction solution is cooled to room temperature, and separation upper organic phase, adds deionized water 200ml, concentrate to pouring 250ml into, filters, and collects solid and obtains product.
Example 12
Reaction flask adds 2-(the chloro-3-methyl-2 of 6-, 4-bis-oxygen-3,4-dihydro-pyrimidin-1 (2H)-methyl)-4-fluorobenzonitrile (29.3g, 0.1mol), acetonitrile (200ml), deionized water (50ml), (R)-3-amino piperidine dihydrochloride (20.7g is added respectively under stirring, 0.12mol), sodium bicarbonate (25g, 0.3mol). 80 degrees Celsius of stirring reactions 6 hours, LC-Ms detection reaction was complete, and reaction solution is cooled to room temperature, and separation upper organic phase, adds deionized water 200ml, concentrate to 250ml, filters, and collects solid and obtains product.
Example 13
Reaction flask adds 2-(the chloro-3-methyl-2 of 6-, 4-bis-oxygen-3,4-dihydro-pyrimidin-1 (2H)-methyl)-4-fluorobenzonitrile (29.3g, 0.1mol), acetone (200ml), adds (R)-3-amino piperidine dihydrochloride (20.7g, 0.12mol) respectively under stirring, triethylamine (30.3g, 0.3mol). 70 degrees Celsius of stirring reactions 3 hours, LC-Ms detection reaction was complete, and reaction solution cold concentration, crude product ethyl acetate and sherwood oil recrystallization obtain product.
Example 14
Reaction flask adds 2-(the chloro-3-methyl-2 of 6-, 4-bis-oxygen-3,4-dihydro-pyrimidin-1 (2H)-methyl)-4-fluorobenzonitrile (293g, 1mol), acetone (2000ml), adds (R)-3-amino piperidine dihydrochloride (207g, 1.2mol) respectively under stirring, diisopropyl ethyl amine (387g, 3mol). 70 degrees Celsius of stirring reactions 3.5 hours, LC-Ms detection reaction was complete, and reaction solution cold concentration, crude product ethyl acetate and sherwood oil recrystallization obtain product.
1HNMR(300MHz,CDCl3)��7.68(dd,J=8.6,5.3Hz,1H),7.07(td,J=8.2,2.5Hz,1H),6.84(dd,J=9.1,2.4Hz,1H),5.38(s,1H),5.33�C5.17(m,2H),3.30(s,3H),3.01(d,J=11.3Hz,1H),2.91(ddd,J=13.0,8.8,3.9Hz,2H),2.60(t,J=10.0Hz,1H),2.49�C2.33(m,1H),2.00�C1.88(m,1H),1.82�C1.71(m,1H),1.59(tdd,J=10.8,7.3,4.0Hz,1H),1.29�C1.12(m,1H).
MS(ESI)M+H=358.38.
Claims (9)
1. a preparation method of bent Ge Lieting, reaction formula is as follows:
In single organic solvent or mixed solvent, by 2-(the chloro-3-methyl-2 of 6-, 4-bis-oxygen-3,4-dihydro-pyrimidin-1 (2H)-methyl)-4-fluorobenzonitrile and (R)-3-amino piperidine dihydrochloride, under the alkaline condition of acid binding agent, carry out synthesis under normal pressure, thus obtain bent Ge Lieting compound.
2. the preparation method of a kind of bent Ge Lieting according to claim 1, it is characterised in that, described single solvent is: tetrahydrofuran (THF), dioxane, methyl alcohol, ethanol, Virahol, the trimethyl carbinol, propyl carbinol, ethylene glycol, acetone or acetonitrile.
3. the preparation method of a kind of bent Ge Lieting according to claim 1, it is characterised in that, described mixed solvent is the mixed solvent mixed by single solvent described in claim 2 and water.
4. the preparation method of a kind of bent Ge Lieting according to claim 1, it is characterised in that, described mixed solvent is the mixed solvent mixed by any 2 kinds of single solvents or the single solvent of more than two kinds of described claim 2.
5. the preparation method of a kind of bent Ge Lieting according to claim 1, it is characterized in that, the solvent of described reaction and reagent 2-(the chloro-3-methyl-2 of 6-, 4-bis-oxygen-3,4-dihydro-pyrimidin-1 (2H)-methyl) mol ratio of-4-fluorobenzonitrile (1) is greater than 5:1, it is preferable that and ratio is 20-50:1.
6. the preparation method of a kind of bent Ge Lieting according to claim 1, it is characterized in that, described reagent 2-(the chloro-3-methyl-2 of 6-, 4-bis-oxygen-3,4-dihydro-pyrimidin-1 (2H)-methyl) ratio of-4-fluorobenzonitrile (1) and (R)-3-amino piperidine dihydrochloride (2) and acid binding agent is 1:0.8-1.2:3-5.
7. the preparation method of a kind of bent Ge Lieting according to claim 1, it is characterised in that, described temperature of reaction is 50 degrees Celsius to 150 degrees Celsius, it is preferable that 60 degrees Celsius to 75 degrees Celsius.
8. the preparation method of a kind of bent Ge Lieting according to claim 1, it is characterised in that, the acid binding agent that described method uses is: sodium carbonate, salt of wormwood, sodium bicarbonate, saleratus, triethylamine or diisopropyl ethyl amine.
9. the preparation method of a kind of bent Ge Lieting according to claim 1, it is characterised in that, the reaction times of described method is 30 minutes to 24 hours, it is preferable that 2 is little of 5 hours.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610138121.1A CN105622575A (en) | 2015-06-16 | 2016-03-11 | Preparation method of Trelagliptin |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2015103332639 | 2015-06-16 | ||
CN201510333263 | 2015-06-16 | ||
CN201610138121.1A CN105622575A (en) | 2015-06-16 | 2016-03-11 | Preparation method of Trelagliptin |
Publications (1)
Publication Number | Publication Date |
---|---|
CN105622575A true CN105622575A (en) | 2016-06-01 |
Family
ID=56037958
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201610138121.1A Pending CN105622575A (en) | 2015-06-16 | 2016-03-11 | Preparation method of Trelagliptin |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN105622575A (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106749228B (en) * | 2016-12-05 | 2018-10-12 | 上海维京生物医药科技有限公司 | A kind of jamaicin drug and the preparation method and application thereof |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101360723A (en) * | 2005-09-16 | 2009-02-04 | 武田药品工业株式会社 | Process for the preparation of pyrimidinedione derivatives |
CN101573351A (en) * | 2006-11-29 | 2009-11-04 | 武田药品工业株式会社 | Polymorphs of succinate salt of 2-[6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2h-pyrimidin-1-ylmethy]-4-fluor-benzonitrile and methods of use therefor |
CN105524042A (en) * | 2014-10-22 | 2016-04-27 | 重庆医药工业研究院有限责任公司 | Method for preparing trelagliptin |
-
2016
- 2016-03-11 CN CN201610138121.1A patent/CN105622575A/en active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101360723A (en) * | 2005-09-16 | 2009-02-04 | 武田药品工业株式会社 | Process for the preparation of pyrimidinedione derivatives |
CN101573351A (en) * | 2006-11-29 | 2009-11-04 | 武田药品工业株式会社 | Polymorphs of succinate salt of 2-[6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2h-pyrimidin-1-ylmethy]-4-fluor-benzonitrile and methods of use therefor |
CN105524042A (en) * | 2014-10-22 | 2016-04-27 | 重庆医药工业研究院有限责任公司 | Method for preparing trelagliptin |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106749228B (en) * | 2016-12-05 | 2018-10-12 | 上海维京生物医药科技有限公司 | A kind of jamaicin drug and the preparation method and application thereof |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN105669645B (en) | Preparation method of trelagliptin and succinate thereof | |
CN106478637B (en) | A kind of impurity and its preparation, detection method of Xi Gelieting | |
Pathare et al. | An efficient protocol for regioselective ring opening of epoxides using sulfated tungstate: application in synthesis of active pharmaceutical ingredients atenolol, propranolol and ranolazine | |
CN105518008A (en) | Amino pyranoid ring derivative and composition and use thereof | |
CN104945299A (en) | Efficient synthesis method of vildagliptin | |
CN105524044A (en) | Trelagliptin impurity and its composition | |
CN103694176B (en) | Preparation method of nilotinib intermediate | |
Wang et al. | Discovery of nitropyridine derivatives as potent HIV-1 non-nucleoside reverse transcriptase inhibitors via a structure-based core refining approach | |
CN107556249A (en) | The preparation method of SYR-322 impurity | |
CN105622575A (en) | Preparation method of Trelagliptin | |
CN102295648B (en) | Calcium cantharidinate and preparation method thereof | |
CN107162921A (en) | The new Phenoxiacetic acid derivatives of one class, its preparation method and its purposes as medicine | |
CN103119051B (en) | The preparation method of Zemuron | |
CN102250110B (en) | Magnesium cantharidate and preparation method thereof | |
CN104151253A (en) | Synthesis method of Alogliptin intermediate | |
CN103601661B (en) | The synthetic method of type II diabetes medicine glimepiride triphosgene | |
CN104311535A (en) | Method for preparing DPP-IV inhibitor | |
CN102746235B (en) | Improved method for preparing imidafenacin | |
CN104672210A (en) | Preparation method of alogliptin and alogliptin benzoate | |
CN105523985A (en) | Preparation method of vildagliptin | |
CN102432594B (en) | Method for preparing 1-(3-hydroxymethylpyridine-2-yl)-2-phenyl-4-methyl piperazine serving as medicinal intermediate | |
CN105001197A (en) | Alogliptin derivative I, preparation method and application thereof | |
CN104693065B (en) | Compound 1-(diphenylmethylene) amino-2-amino-2-methyl propane and its preparation method and application | |
CN105085475B (en) | A method of synthesis Egelieting intermediate | |
CN103408552B (en) | Method for preparing Alisertib |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
WD01 | Invention patent application deemed withdrawn after publication | ||
WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20160601 |