CN105061247A - Improved synthesis method for dencichine - Google Patents
Improved synthesis method for dencichine Download PDFInfo
- Publication number
- CN105061247A CN105061247A CN201510511479.XA CN201510511479A CN105061247A CN 105061247 A CN105061247 A CN 105061247A CN 201510511479 A CN201510511479 A CN 201510511479A CN 105061247 A CN105061247 A CN 105061247A
- Authority
- CN
- China
- Prior art keywords
- dencichine
- reaction
- hours
- room temperature
- synthetic method
- 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
- NEEQFPMRODQIKX-REOHCLBHSA-N N(3)-oxalyl-L-2,3-diaminopropionic acid Chemical compound OC(=O)[C@@H](N)CNC(=O)C(O)=O NEEQFPMRODQIKX-REOHCLBHSA-N 0.000 title claims abstract description 39
- 238000001308 synthesis method Methods 0.000 title abstract 3
- 238000006243 chemical reaction Methods 0.000 claims abstract description 29
- 239000007787 solid Substances 0.000 claims abstract description 14
- 238000000605 extraction Methods 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims abstract description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 27
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 21
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 15
- 238000010189 synthetic method Methods 0.000 claims description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 239000012046 mixed solvent Substances 0.000 claims description 8
- KRJLRVZLNABMAT-YFKPBYRVSA-N (2s)-3-amino-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@@H](CN)C(O)=O KRJLRVZLNABMAT-YFKPBYRVSA-N 0.000 claims description 7
- MFPWEWYKQYMWRO-UHFFFAOYSA-N tert-butyl carboxy carbonate Chemical compound CC(C)(C)OC(=O)OC(O)=O MFPWEWYKQYMWRO-UHFFFAOYSA-N 0.000 claims description 7
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- ZBIKORITPGTTGI-UHFFFAOYSA-N [acetyloxy(phenyl)-$l^{3}-iodanyl] acetate Chemical compound CC(=O)OI(OC(C)=O)C1=CC=CC=C1 ZBIKORITPGTTGI-UHFFFAOYSA-N 0.000 claims description 6
- 239000008346 aqueous phase Substances 0.000 claims description 6
- 238000001953 recrystallisation Methods 0.000 claims description 6
- JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 claims description 5
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical class OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 5
- 239000012043 crude product Substances 0.000 claims description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 230000002378 acidificating effect Effects 0.000 claims description 4
- 239000003637 basic solution Substances 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- 235000015320 potassium carbonate Nutrition 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 3
- 238000004090 dissolution Methods 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 2
- 239000011707 mineral Substances 0.000 claims description 2
- 235000010755 mineral Nutrition 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 239000000047 product Substances 0.000 claims description 2
- 239000002994 raw material Substances 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 239000000243 solution Substances 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 3
- 238000004904 shortening Methods 0.000 abstract description 2
- 230000023555 blood coagulation Effects 0.000 abstract 1
- 238000003889 chemical engineering Methods 0.000 abstract 1
- 230000023597 hemostasis Effects 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 238000003786 synthesis reaction Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- 229960001230 asparagine Drugs 0.000 description 2
- 206010053567 Coagulopathies Diseases 0.000 description 1
- 102100027378 Prothrombin Human genes 0.000 description 1
- 108010094028 Prothrombin Proteins 0.000 description 1
- 230000035602 clotting Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 229940039716 prothrombin Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses an improved synthesis method for dencichine, and belongs to the fields of medicine and chemical engineering. Dencichine is a white solid, and can be used for hemostasis by shortening blood coagulation time and thrombinogen time, thereby being important medicine; while, natural dencichine is low in extraction rate, and low in profit margin. The improved synthesis method is an efficient way to obtain dencichine according to a chemosynthesis method, and is low in cost, suitable for industrial production, and low in reaction cost, thereby providing an important reference for industrialization.
Description
Technical field
The present invention relates to a kind of improvement of synthetic method of dencichine, belong to medicine, chemical technology field.
Background technology
Dencichine is a kind of white solid, and dencichine plays anastalsis by shortening clotting time, prothrombin time etc., is a kind of important medical body.But natural dencichine extraction yield is low, and profit margin is little.This method is a kind of effective way being obtained dencichine by chemical synthesis process, and with low cost, can suitability for industrialized production.
Summary of the invention
This patent, by the exploration of dencichine building-up process and optimization, finally obtains the synthesis technique of synthesis dencichine.Dencichine is a kind of important medical body.
The synthetic method of dencichine of the present invention, be adopt altheine to be raw material, react with tert-Butyl dicarbonate under room temperature in basic solution, obtain Boc-L-l-asparagine, Boc-L-l-asparagine reacts with iodobenzene diacetate in acidic mixed solvent system, obtain degraded product Boc-L-2,3-diaminopropionic acid, Boc-L-2,3-diaminopropionic acid and oxalyl chloride are 1, in 4-dioxane, room temperature reaction 6 hours, obtains crude product dencichine after process, and recrystallization obtains sterling dencichine.
The synthetic method of above-mentioned dencichine, is characterized in that: described basic solution, refers to the acetone and water mixed solvent that are dissolved with salt of wormwood or sodium hydroxide, alkali used does not singly refer to salt of wormwood and sodium hydroxide, also comprises sodium carbonate, potassium hydroxide, sodium bicarbonate, the mineral alkalis such as saleratus.
The synthetic method of above-mentioned dencichine, is characterized in that: described acidic mixed solvent system, refers to the mixed solvent system of acetonitrile, ethyl, saturated citric acid solution and water, organic solvent used does not singly only have acetonitrile and ethyl acetate, also comprise acetone, DMF.
The synthetic method of above-mentioned dencichine, is characterized in that: described Boc-L-2,3-diaminopropionic acid and oxalyl chloride room temperature reaction 6 hours in Isosorbide-5-Nitrae-dioxane.Solvent wherein does not singly refer to Isosorbide-5-Nitrae-dioxane, also comprises tetrahydrofuran (THF), acetonitrile and acetone.Wherein react 6 hours, also comprise reaction 1 to 12 hour.
The synthetic method of above-mentioned dencichine, is characterized in that: the synthetic method of described dencichine obtains: get 6.01g sodium hydroxide, be dissolved in 100mL water, be cooled to 0 degree, add 20gL-l-asparagine, stir after 30 minutes, add 200mL acetone and 31.4gK
2cO
3, keep temperature not higher than 5 degree, drip 39.6g tert-Butyl dicarbonate, rise to room temperature reaction after 24 hours, after adding 300mL water dissolution, after 0.5mol/LHCl regulates pH to 6-7, extraction (methylene dichloride: methyl alcohol, 4:1, 200mL × 5), retain aqueous phase, after aqueous phase regulates pH to 3-4 with 0.5mol/LHCl, extraction (methylene dichloride: methyl alcohol, 4:1, 200mL × 10), anhydrous sodium sulfate drying, after being spin-dried for, obtain 33gBoc-L-l-asparagine, 33gBoc-L-l-asparagine is dissolved in 96mL ethyl acetate, 96mL acetonitrile, in the saturated citric acid of 1.0mL and 48mL water, after being cooled to 0 degree, add 33.3g iodobenzene diacetate in batches, rise to room temperature reaction 4 hours, solid is had to separate out, after reaction system is down to 0 degree, filter the solid of separating out in reaction, solid is spin-dried for, obtain 30gBoc-L-2, 3-diaminopropionic acid, 30gBoc-L-2, 3-diaminopropionic acid is dissolved in 200mL1, in 4-dioxane, after dissolving completely, after being cooled to 0 degree, slow dropping 20g oxalyl chloride, rise to room temperature reaction 5 hours, after the cancellation that adds water reaction, solid is had to separate out, filter, washing, dry, obtain crude product dencichine, after recrystallization, obtain 40g sterling dencichine.
Above-mentioned with L-asparagine, tert-Butyl dicarbonate, iodobenzene diacetate and oxalyl chloride etc. are that the chemical reaction of Material synthesis dencichine and reaction formula are as follows:
(1) reaction equation of L-asparagine and tert-Butyl dicarbonate is:
(2) reacted, the DeR equation of Boc-L-l-asparagine is:
(3) reacted, the reaction equation of Boc-L-2,3-diaminopropionic acid and oxalyl chloride is:
(4) after having reacted, add water cancellation, after recrystallization, obtains 40g dencichine sterling.
Embodiment
Embodiment:
The synthetic method of described dencichine obtains: get 6.01g sodium hydroxide, be dissolved in 100mL water, be cooled to 0 degree, add 20gL-l-asparagine, stir after 30 minutes, add 200mL acetone and 31.4gK
2cO
3, keep temperature not higher than 5 degree, drip 39.6g tert-Butyl dicarbonate, rise to room temperature reaction after 24 hours, after adding 300mL water dissolution, after 0.5mol/LHCl regulates pH to 6-7, extraction (methylene dichloride: methyl alcohol, 4:1, 200mL × 5), retain aqueous phase, after aqueous phase regulates pH to 3-4 with 0.5mol/LHCl, extraction (methylene dichloride: methyl alcohol, 4:1, 200mL × 10), anhydrous sodium sulfate drying, after being spin-dried for, obtain 33gBoc-L-l-asparagine, 33gBoc-L-l-asparagine is dissolved in 96mL ethyl acetate, 96mL acetonitrile, in the saturated citric acid of 1.0mL and 48mL water, after being cooled to 0 degree, add 33.3g iodobenzene diacetate in batches, rise to room temperature reaction 4 hours, solid is had to separate out, after reaction system is down to 0 degree, filter the solid of separating out in reaction, solid is spin-dried for, obtain 30gBoc-L-2, 3-diaminopropionic acid, 30gBoc-L-2, 3-diaminopropionic acid is dissolved in 200mL1, in 4-dioxane, after dissolving completely, after being cooled to 0 degree, slow dropping 20g oxalyl chloride, rise to room temperature reaction 5 hours, after the cancellation that adds water reaction, solid is had to separate out, filter, washing, dry, obtain crude product dencichine, after recrystallization, obtain 40g sterling dencichine.
Claims (5)
1. the synthetic method of a dencichine is improved, be adopt altheine to be raw material, react with tert-Butyl dicarbonate under room temperature in basic solution, obtain Boc-L-l-asparagine, Boc-L-l-asparagine reacts with iodobenzene diacetate in acidic mixed solvent system, obtain degraded product Boc-L-2,3-diaminopropionic acid, Boc-L-2,3-diaminopropionic acid and oxalyl chloride are 1, in 4-dioxane, room temperature reaction 6 hours, obtains crude product dencichine after process, and recrystallization obtains sterling dencichine.
2. the synthetic method of dencichine as claimed in claim, it is characterized in that: described basic solution, refer to the acetone and water mixed solvent that are dissolved with salt of wormwood or sodium hydroxide, alkali used does not singly refer to salt of wormwood and sodium hydroxide, also comprise sodium carbonate, potassium hydroxide, sodium bicarbonate, the mineral alkalis such as saleratus.
3. the synthetic method of dencichine as claimed in claim, it is characterized in that: described acidic mixed solvent system, refer to the mixed solvent system of acetonitrile, ethyl, saturated citric acid solution and water, organic solvent used does not singly only have acetonitrile and ethyl acetate, also comprise acetone, DMF.
4. the synthetic method of dencichine as claimed in claim, is characterized in that: described Boc-L-2,3-diaminopropionic acid and oxalyl chloride room temperature reaction 6 hours in Isosorbide-5-Nitrae-dioxane.Solvent wherein does not singly refer to Isosorbide-5-Nitrae-dioxane, also comprises tetrahydrofuran (THF), acetonitrile and acetone.Wherein react 6 hours, also comprise reaction 1 to 12 hour.
5. the synthetic method of dencichine as claimed in claim, is characterized in that: the synthetic method of described dencichine obtains: get 6.01g sodium hydroxide, be dissolved in 100mL water, be cooled to 0 degree, add 20gL-l-asparagine, stir after 30 minutes, add 200mL acetone and 31.4gK
2cO
3, keep temperature not higher than 5 degree, drip 39.6g tert-Butyl dicarbonate, rise to room temperature reaction after 24 hours, after adding 300mL water dissolution, after 0.5mol/LHCl regulates pH to 6-7, extraction (methylene dichloride: methyl alcohol, 4:1, 200mL × 5), retain aqueous phase, after aqueous phase regulates pH to 3-4 with 0.5mol/LHCl, extraction (methylene dichloride: methyl alcohol, 4:1, 200mL × 10), anhydrous sodium sulfate drying, after being spin-dried for, obtain 33gBoc-L-l-asparagine, 33gBoc-L-l-asparagine is dissolved in 96mL ethyl acetate, 96mL acetonitrile, in the saturated citric acid of 1.0mL and 48mL water, after being cooled to 0 degree, add 33.3g iodobenzene diacetate in batches, rise to room temperature reaction 4 hours, solid is had to separate out, after reaction system is down to 0 degree, filter the solid of separating out in reaction, solid is spin-dried for, obtain 30gBoc-L-2, 3-diaminopropionic acid, 30gBoc-L-2, 3-diaminopropionic acid is dissolved in 200mL1, in 4-dioxane, after dissolving completely, after being cooled to 0 degree, slow dropping 20g oxalyl chloride, rise to room temperature reaction 5 hours, after the cancellation that adds water reaction, solid is had to separate out, filter, washing, dry, obtain crude product dencichine, after recrystallization, obtain 40g sterling dencichine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510511479.XA CN105061247A (en) | 2015-08-19 | 2015-08-19 | Improved synthesis method for dencichine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510511479.XA CN105061247A (en) | 2015-08-19 | 2015-08-19 | Improved synthesis method for dencichine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105061247A true CN105061247A (en) | 2015-11-18 |
Family
ID=54490822
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510511479.XA Pending CN105061247A (en) | 2015-08-19 | 2015-08-19 | Improved synthesis method for dencichine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105061247A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105439883A (en) * | 2015-12-11 | 2016-03-30 | 中国医学科学院药用植物研究所 | Preparation method and application of D-dencichine |
| CN109180532A (en) * | 2018-08-29 | 2019-01-11 | 南京天际联盟医药科技有限公司 | The high efficiency preparation method of D- dencichine |
| CN112125819A (en) * | 2020-08-19 | 2020-12-25 | 兰州百源基因技术有限公司 | Preparation method of sanchinin |
| CN113754551A (en) * | 2021-09-13 | 2021-12-07 | 云南西草资源开发有限公司 | Preparation method of hemostatic raw material sanchinin |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1292377A (en) * | 2000-08-10 | 2001-04-25 | 昆明南国生物资源开发研究所 | Synthesis preparation method of high-effective hemostatic notoginseng extract |
| CN1292376A (en) * | 2000-08-10 | 2001-04-25 | 昆明南国生物资源开发研究所 | Synthesis method for preparing high-effective hemostatic notogiseng extract |
-
2015
- 2015-08-19 CN CN201510511479.XA patent/CN105061247A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1292377A (en) * | 2000-08-10 | 2001-04-25 | 昆明南国生物资源开发研究所 | Synthesis preparation method of high-effective hemostatic notoginseng extract |
| CN1292376A (en) * | 2000-08-10 | 2001-04-25 | 昆明南国生物资源开发研究所 | Synthesis method for preparing high-effective hemostatic notogiseng extract |
Non-Patent Citations (1)
| Title |
|---|
| LIN-HUA ZHANG ET AL.: "The Enantiospecific Synthesis of an Isoxazoline. A RGD Mimic Platelet GPIIb/IIIa Antagonist", 《J. ORG. CHEM.》 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105439883A (en) * | 2015-12-11 | 2016-03-30 | 中国医学科学院药用植物研究所 | Preparation method and application of D-dencichine |
| CN109180532A (en) * | 2018-08-29 | 2019-01-11 | 南京天际联盟医药科技有限公司 | The high efficiency preparation method of D- dencichine |
| CN109180532B (en) * | 2018-08-29 | 2021-04-16 | 南京天际联盟医药科技有限公司 | High-efficiency preparation method of D-dencichine |
| CN112125819A (en) * | 2020-08-19 | 2020-12-25 | 兰州百源基因技术有限公司 | Preparation method of sanchinin |
| CN112125819B (en) * | 2020-08-19 | 2023-07-25 | 兰州百源基因技术有限公司 | Preparation method of dencichine |
| CN113754551A (en) * | 2021-09-13 | 2021-12-07 | 云南西草资源开发有限公司 | Preparation method of hemostatic raw material sanchinin |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105061247A (en) | Improved synthesis method for dencichine | |
| CN107311875A (en) | The synthetic method of aramine | |
| CN103833593B (en) | A kind of preparation method of N-(the 9-fluorenylmethyloxycarbonyl)-O-tert-butyl group-TYR | |
| CN102993184A (en) | Esomeprazole and preparation method of magnesium trihydrate of esomeprazole | |
| CN104356146B (en) | A kind of preparation method of cefotiam chloride | |
| CN105399667A (en) | Preparation method of edoxaban intermediate | |
| CN102001992A (en) | Method for preparing clevidipine butyrate | |
| CN104892444B (en) | A kind of method of synthesizing D-p-hydroxyphenylglycine methyl ester | |
| CN103012300A (en) | Novel method for preparing valsartan | |
| CN103664888A (en) | Preparation method of esomeprazole trihydrate | |
| CN103804266B (en) | A kind of synthetic method of vildagliptin intermediate | |
| CN104478974A (en) | Synthesis method of 20,23-dipiperidino-5-O-mycaminose-tylosin lactone | |
| CN1931857A (en) | Prepn process of 5-losartan carboxylate | |
| CN105367391B (en) | A kind of preparation method of the trimethoxy-ethane of 2 chlorine 1,1,1 | |
| CN109748813A (en) | A kind of synthetic method improvement of dencichine | |
| CN104844597A (en) | Synthesis method of 6-chlorine-8-methoxy ethyl formate imidazole and [1,2a]pyridine-3-ethyl formate | |
| CN108948001A (en) | The synthetic route of 1R, 3S-1- methyl tetrahydro-beta-carboline -3- carboxylic acid, anti-thrombus activity and application | |
| CN104211644B (en) | A kind of synthetic method of 3,4-dichloro-pyridazine | |
| CN105061375A (en) | Method for preparing 3-isochromanone | |
| CN106397416B (en) | A kind of preparation method of Tegafur | |
| CN103408418A (en) | Preparation and purification method of solid malonic acid | |
| CN105017113A (en) | Research and development of ally isothiocyanate | |
| CN102827060B (en) | Synthetic method of 5-trifluoromethyl pyrrole-2-formic acid | |
| CN107793420A (en) | A kind of synthetic method of 3,4 dihydro 2H pyrans [3,2 b] pyridines | |
| CN104844599A (en) | Synthesis method of 6-bromine-8-methoxy ethyl formate imidazole and [1,2a]pyridine-3-ethyl formate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB02 | Change of applicant information |
Address after: 710000 Shaanxi city of Xi'an province high tech Zone Jinye Road No. 69 C District No. 1 gazelle Valley F building 501 room Applicant after: Xi'an Yue biological Polytron Technologies Inc Address before: 710000 Shaanxi city of Xi'an province high tech Zone Jinye Road No. 69 C District No. 1 gazelle Valley F building 501 room Applicant before: Xi'an Day Natural Tech Co., Ltd. |
|
| COR | Change of bibliographic data | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20151118 |
|
| RJ01 | Rejection of invention patent application after publication |