CN103183649A - Preparation method of 2-amino-6-propylamino-4,5,6,7-tetrahydrobenzothiazole - Google Patents
Preparation method of 2-amino-6-propylamino-4,5,6,7-tetrahydrobenzothiazole Download PDFInfo
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- CN103183649A CN103183649A CN2011104595629A CN201110459562A CN103183649A CN 103183649 A CN103183649 A CN 103183649A CN 2011104595629 A CN2011104595629 A CN 2011104595629A CN 201110459562 A CN201110459562 A CN 201110459562A CN 103183649 A CN103183649 A CN 103183649A
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Abstract
The invention provides a preparation method of 2-amino-6-propylamino-4,5,6,7-tetrahydrobenzothiazole. According to the preparation method, 2-amino-6- propionamido-4,5,6,7-tetrahydrobenzothiazole is adopted as a raw material and is reduced through I2 and sodium borohydride to prepare the 2-amino-6-propylamino-4,5,6,7-tetrahydrobenzothiazole. The preparation method has the advantages that the raw material is easy to obtain, the reaction condition is mild, the control is easy and the reaction safety is high; and the preparation method is suitable for industrial production.
Description
Technical field
The invention belongs to medical technical field, be specifically related to a kind of 2-amino-6-third amino-4,5,6, the preparation method of 7-tetrahydro benzothiazol.
Background technology
2-amino-6-third amino-4,5,6, the 7-tetrahydro benzothiazol, structural formula is as follows:
The DL body can obtain product (S)-(-) 2-amino-6-third amino-4,5,6 through splitting, and 7-tetrahydro benzothiazol, its dihydrochloride are body of Pramipexole dihydrochloride, and wherein (S) is expressed as the S configuration, and (-) is expressed as left-handed.Body of Pramipexole dihydrochloride can be used as medical material, is used for the treatment of parkinsonian medicine, and body of Pramipexole dihydrochloride must be the S configuration, left-handed just have a medical effect.Prepare the 2-amino-6-of (S)-(-) third amino-4,5,6 in the synthetic hydrochloric acid pramipexole at present, the method for 7-tetrahydro benzothiazol mainly contains:
J.Med.chem.1987,30,494-498 disclose a kind of preparation method of body of Pramipexole dihydrochloride, and this method is with the 2-of (S)-(-) amino-6-propionamido-4,5,6, and the 7-tetrahydro benzothiazol is raw material, logical N in tetrahydrofuran (THF)
2Protection down obtains the 2-amino-6-of (S)-(-) third amino-4,5,6, the 7-tetrahydro benzothiazol with the borine solution reaction of tetrahydrofuran (THF).This preparation method's particular content is: at the logical N of room temperature
2Protection is containing the 2-of (S)-(-) amino-6-propionamido-4,5,6 down, dropwise adds the borine solution of tetrahydrofuran (THF) in the tetrahydrofuran solution of 7-tetrahydro benzothiazol, stirs 1 hour down and cooling at 50 ℃ then, adds water and concentrated hydrochloric acid again.Evaporate tetrahydrofuran (THF) and add 25% sodium hydroxide solution to aqueous phase, filter precipitation (the 2-amino-6-of (S)-(-) third amino-4,5,6 that obtain then, the 7-tetrahydro benzothiazol), the precipitation that obtains is washed and it is dissolved in the ethyl acetate of heat.The moisture of removing in the solution also concentrates, and filters and obtains precipitation, uses the ethyl acetate washing precipitation, obtains the 2-amino-6-of (S)-(-) third amino-4,5,6, the 7-tetrahydro benzothiazol.The shortcoming of this method is the borine solution manufacture method complexity of tetrahydrofuran (THF), is not suitable for suitability for industrialized production, and because the colourless severe toxicity of borine is inflammable and explosive, the facile hydrolysis poor stability be difficult for preserving transportation, so production security is poor.
Chinese patent CN1834092B replaces borine with the diethyl ether solution of boron trifluoride, because the diethyl ether solution of boron trifluoride also is highly toxic product, inflammable and explosive, and the diethyl ether solution of boron trifluoride is met moisture hydrolysis immediately in air, generate the fluorochemical smog of severe toxicity, severe reaction conditions also is unfavorable for suitability for industrialized production.
Summary of the invention
The objective of the invention is to be difficult for making in order to overcome aforesaid method, the low shortcoming that is unfavorable for suitability for industrialized production of reaction safety, provide a kind of raw material be simple and easy to, 2-amino-6-third amino-4,5,6 that reaction safety is high, the preparation method of 7-tetrahydro benzothiazol.
Preparation method provided by the invention is with 2-amino-6-propionamido-4,5,6, and the 7-tetrahydro benzothiazol is raw material, passes through I
2And sodium borohydride reduction, preparation 2-amino-6-third amino-4,5,6,7-tetrahydro benzothiazol.This preparation method's raw material is simple and easy to, and the reaction conditions gentleness is easy to control, and this preparation method's reaction safety is improved.
2-amino-6-third amino-4,5,6 provided by the invention, the preparation method of 7-tetrahydro benzothiazol can be represented by following reaction equation:
In reaction equation, described 2-amino-6-propionamido-4,5,6,7-tetrahydro benzothiazol, NaBH
4And I
2Mol ratio be 1: 2: 1-1: 15: 8, be preferably 1: 5: 2-1: 9: 4.
Described tetrahydrofuran (THF) uses as solvent, and its volumetric usage is NaBH
4The 10-25 of weight is (volume/weight, unit is mL/g) doubly.
Described rare gas element refers to not the gas with reactant generation chemical reaction, as in the gas of zero group in nitrogen, the periodic table of elements one or more, is preferably nitrogen.
When reaction, 2-amino-6-propionamido-4,5,6,7-tetrahydro benzothiazol, NaBH
4And I
2Order be preferably, earlier with NaBH
4Join in the reaction solvent, and then add 2-amino-6-propionamido-4,5,6,7-tetrahydro benzothiazol and I respectively
2Under the preferable case, in the adition process of three kinds of reactants, constantly stir, and remain on below 10 ℃, be preferably 0-5 ℃.Described I
2With I
2With tetrahydrofuran (THF) or I
2With organic ether or I
2Add with the solution form of the mixed solution of tetrahydrofuran (THF) and organic ether, described organic ether is preferably ether.
Described I
2With tetrahydrofuran (THF) or I
2With organic ether or I
2With the strength of solution of the mixed solution of tetrahydrofuran (THF) and organic ether be the 0.4-1.5 mol, be preferably the 0.8-1.0 mol.Organic ethers and tetrahydrofuran (THF) volume ratio are preferably 1: 1-1: 2.
After above-mentioned reactant mixes, 2-amino-6-propionamido-4,5,6,7-tetrahydro benzothiazol, NaBH
4And I
2Catalytic temperature of reaction is 0-80 ℃, is preferably 0-50 ℃, and the reaction times was at least 2 hours, was preferably 12-36 hour, more preferably 24-30 hour.Under the preferable case, adopt the mode of segmentation reaction, namely reacted 10-14 hour down at 0-5 ℃, 30-50 ℃ of reaction 6-10 hour, reaction was finished, and cooled off down at 0-5 ℃.
Described 2-amino-6-third amino-4,5,6, the separation of 7-tetrahydro benzothiazol can be adopted known method, as add hydrochloric acid soln, hydrochloric acid and 2-amino-6-third amino-4,5,6, the reaction of 7-tetrahydro benzothiazol generates 2-amino-6-third amino-4,5,6,7-tetrahydro benzothiazol one hydrochloride and/or dihydrochloride evaporate tetrahydrofuran (THF) then.The resistates that evaporates behind the tetrahydrofuran (THF) is soluble in water, add basic solution, as sodium hydroxide solution, sodium carbonate solution or ammoniacal liquor, the solution pH value is adjusted to 9-10, this moment 2-amino-6-third amino-4,5,6,7-tetrahydro benzothiazol, one hydrochloride and/or dihydrochloride and basic solution reaction generate 2-amino-6-third amino-4,5,6,7-tetrahydro benzothiazol obtains 2-amino-6-third amino-4 with organic solvent extraction, adding anhydrous sodium sulfate drying, evaporating solvent, 5,6,7-tetrahydro benzothiazol, drying obtains solid product.The volume of described hydrochloric acid soln is NaBH
415-25 doubly (volume/weight, unit is mL/g), the concentration of described hydrochloric acid soln is 15-25%; Described solvent is one or more in ethyl acetate, methylene dichloride, the ether, is preferably ethyl acetate; Described drying can adopt known method and technology, as seasoning, heat drying, forced air drying, vacuum-drying etc.
According to 2-amino-6-third amino-4,5,6 that preparation method provided by the invention obtains, 7-tetrahydro benzothiazol, product yield 60%.
Embodiment
The following examples will be done to explain more specifically to the present invention, but the present invention is not limited only to these embodiment, and these embodiment do not limit the present invention in any way yet equally.
Embodiment 1
With 0.18 mole of NaBH
4Join in three mouthfuls of reaction flasks of the anhydrous tetrahydro furan that fills 50 milliliters, feed nitrogen protection, under 0-5 ℃ of continuous stirring condition; 2-amino-6-the propionamido-4,5 that adds 0.02 mole, 6; the 7-tetrahydro benzothiazol slowly splashes into 100 milliliters of 0.08 mole of I after the mixing back is even again
2Tetrahydrofuran solution (0.08 mole of I
2), the time is 3-4 hour.Control temperature 0-5 ℃ of continuous stirring reaction 10 hours then, again reaction mixture is heated to 50 ℃ of reactions 12 hours.Under ice bath, cool off then.
Add 350 ml concns in the above-mentioned post reaction mixture and be 10% hydrochloric acid soln, NaOH solution with 20% is regulated pH value to 9-10, extract with the ethyl acetate gradation, add anhydrous sodium sulfate drying in the extracting solution, evaporating solvent obtains solid product, and vacuum-drying obtains 2.54 gram 2-amino-6-third amino-4,5,6,7-tetrahydro benzothiazol, product yield 60%.
(
1H-NMR(400MHz,DMSO);δ(PPm):δ6.57(s,2H),δ2.806-2.755(m,1H),δ2.719-2.681(dd,1H),δ2.522-2.486(t,2H),δ2.454-2.349(m,2H),δ2.219-2.160(q,1H),δ1.902-1.870(m,1H),δ1.506-1.457(m,2H),δ1.449-1.365(m,2H),δ0.875-0.837(t,3H)。
Embodiment 2
With 0.18 mole of NaBH
4Join in three mouthfuls of reaction flasks of the anhydrous tetrahydro furan that fills 50 milliliters, feed nitrogen protection, under 0-5 ℃ of continuous stirring condition; 2-amino-6-the propionamido-4,5 that adds 0.02 mole, 6; the 7-tetrahydro benzothiazol mixes the I that the back slowly splashes into 100 milliliters 0.08 mole after evenly again
2Tetrahydrofuran (THF), diethyl ether solution (0.08 mole of I
2, tetrahydrofuran (THF) and ether volume ratio are 1: 1), reaction is 12 hours under the 0-5 ℃ of continuous stirring condition, reaction mixture is heated to 35 ℃ of reactions 12 hours again, cools off under ice bath then.
Add 360 ml concns in the above-mentioned post reaction mixture and be 10% hydrochloric acid soln, NaOH solution with 20% is regulated pH value to 9-10, extract with the ethyl acetate gradation, add anhydrous sodium sulfate drying in the extracting solution, evaporating solvent obtains solid product, and vacuum-drying obtains 2.75 gram 2-amino-6-third amino-4,5,6,7-tetrahydro benzothiazol, product yield 65%.
(
1H-NMR(400MHz,DMSO);δ(PPm):δ6.57(s,2H),δ2.806-2.755(m,1H),δ2.719-2.681(dd,1H),δ2.522-2.486(t,2H),δ2.454-2.349(m,2H),δ2.219-2.160(q,1H),δ1.902-1.870(m,1H),δ1.506-1.457(m,2H),δ1.449-1.365(m,2H),δ0.875-0.837(t,3H)。
Embodiment 3
With 0.04 mole of NaBH
4Join in three mouthfuls of reaction flasks of the anhydrous tetrahydro furan that fills 50 milliliters, feed nitrogen protection, under 0-5 ℃ of continuous stirring condition; 2-amino-6-the propionamido-4,5 that adds 0.02 mole, 6; the 7-tetrahydro benzothiazol mixes the I that the back slowly splashes into 100 milliliters 0.16 mole after evenly again
2Tetrahydrofuran (THF), diethyl ether solution (0.16 mole of I
2, tetrahydrofuran (THF) and ether volume ratio are 1: 4), reaction is 12 hours under the 0-5 ℃ of continuous stirring condition, reaction mixture is heated to 40 ℃ of reactions 20 hours again, cools off under ice bath then.
Add 360 ml concns in the above-mentioned post reaction mixture and be 10% hydrochloric acid soln, NaOH solution with 20% is regulated pH value to 9-10, extract with the ethyl acetate gradation, add anhydrous sodium sulfate drying in the extracting solution, evaporating solvent obtains solid product, and vacuum-drying obtains 2.33 gram 2-amino-6-third amino-4,5,6,7-tetrahydro benzothiazol, product yield 55%.
(
1H-NMR(400MHz,DMSO);δ(PPm):δ6.57(s,2H),δ2.806-2.755(m,1H),δ2.719-2.681(dd,1H),δ2.522-2.486(t,2H),δ2.454-2.349(m,2H),δ2.219-2.160(q,1H),δ1.902-1.870(m,1H),δ1.506-1.457(m,2H),δ1.449-1.365(m,2H),δ0.875-0.837(t,3H)。
Embodiment 4
With 0.3 mole of NaBH
4Join in three mouthfuls of reaction flasks of the anhydrous tetrahydro furan that fills 50 milliliters, feed nitrogen protection, under 0-5 ℃ of continuous stirring condition; 2-amino-6-the propionamido-4,5 that adds 0.02 mole, 6; the 7-tetrahydro benzothiazol slowly splashes into 100 milliliters of 0.12 mole of I after the mixing back is even again
2Tetrahydrofuran solution (0.12 mole of I
2), the time is 3-4 hour.Control temperature 0-5 ℃ of continuous stirring reaction 10 hours then, again reaction mixture is heated to 70 ℃ of reactions 10 hours.Under ice bath, cool off then.
Add 350 ml concns in the above-mentioned post reaction mixture and be 10% hydrochloric acid soln, NaOH solution with 20% is regulated pH value to 9-10, extract with the ethyl acetate gradation, add anhydrous sodium sulfate drying in the extracting solution, evaporating solvent obtains solid product, and vacuum-drying obtains 2.46 gram 2-amino-6-third amino-4,5,6,7-tetrahydro benzothiazol, product yield 58%.
(
1H-NMR(400MHz,DMSO);δ(PPm):δ6.57(s,2H),δ2.806-2.755(m,1H),δ2.719-2.681(dd,1H),δ2.522-2.486(t,2H),δ2.454-2.349(m,2H),δ2.219-2.160(q,1H),δ1.902-1.870(m,1H),δ1.506-1.457(m,2H),δ1.449-1.365(m,2H),δ0.875-0.837(t,3H)。
Embodiment 5
With 0.1 mole of NaBH
4Join in three mouthfuls of reaction flasks of the anhydrous tetrahydro furan that fills 50 milliliters, feed nitrogen protection, under 0-5 ℃ of continuous stirring condition; 2-amino-6-the propionamido-4,5 that adds 0.02 mole, 6; the 7-tetrahydro benzothiazol slowly splashes into 100 milliliters of 0.04 mole of I after the mixing back is even again
2Tetrahydrofuran solution (0.04 mole of I
2), the time is 3-4 hour.Control temperature 0-5 ℃ of continuous stirring reaction 10 hours then, again reaction mixture is heated to 80 ℃ of reactions 24 hours.Under ice bath, cool off then.
Add 350 ml concns in the above-mentioned post reaction mixture and be 10% hydrochloric acid soln, NaOH solution with 20% is regulated pH value to 9-10, extract with the ethyl acetate gradation, add anhydrous sodium sulfate drying in the extracting solution, evaporating solvent obtains solid product, and vacuum-drying obtains 2.2 gram 2-amino-6-third amino-4,5,6,7-tetrahydro benzothiazol, product yield 52%.
(
1H-NMR(400MHz,DMSO);δ(PPm):δ6.57(s,2H),δ2.806-2.755(m,1H),δ2.719-2.681(dd,1H),δ2.522-2.486(t,2H),δ2.454-2.349(m,2H),δ2.219-2.160(q,1H),δ1.902-1.870(m,1H),δ1.506-1.457(m,2H),δ1.449-1.365(m,2H),δ0.875-0.837(t,3H)。
Claims (10)
1. 2-amino-6-third amino-4,5,6, the preparation method of 7-tetrahydro benzothiazol is characterized in that, under protection of inert gas, with 2-amino-6-propionamido-4,5,6,7-tetrahydro benzothiazol and NaBH
4And I
2Contact reacts in reaction solvent is isolated 2-amino-6-third amino-4,5,6, the 7-tetrahydro benzothiazol.
2. method according to claim 1 is characterized in that, described 2-amino-6-propionamido-4,5,6,7-tetrahydro benzothiazol and NaBH
4And I
2Mol ratio be 1: (2-15): (1-8).
3. method according to claim 2 is characterized in that, described 2-amino-6-propionamido-4,5,6,7-tetrahydro benzothiazol and NaBH
4And I
2Mol ratio be 1: (5-9): (2-4).
4. method according to claim 1 is characterized in that, described reaction solvent is any of mixed solution of tetrahydrofuran (THF), organic ethers, tetrahydrofuran (THF) and organic ethers, the consumption of reaction solvent and NaBH
4Envelope-bulk to weight ratio be 10-25, unit is mL/g.
5. method according to claim 1 is characterized in that, described rare gas element is one or more in the gas of zero group in nitrogen, the periodic table of elements, is preferably nitrogen.
6. method according to claim 1 is characterized in that, described 2-amino-6-propionamido-4,5,6,7-tetrahydro benzothiazol and NaBH
4And I
2Addition sequence be earlier with NaBH
4Join in the reaction solvent, and then add 2-amino-6-propionamido-4,5,6,7-tetrahydro benzothiazol and I
2, and keep 0-10 ℃ of temperature.
7. method according to claim 6 is characterized in that, described I
2With I
2With tetrahydrofuran (THF), I
2With organic ethers, I
2Add with any solution form of the mixed solution of tetrahydrofuran (THF) and organic ether; Described organic ether and tetrahydrofuran (THF) volume ratio are 1: 1-1: 4, and described I
2The concentration of solution is the 0.4-1.5 mol.
8. method according to claim 1 is characterized in that, 2-amino-6-propionamido-4,5,6,7-tetrahydro benzothiazol and NaBH
4And I
2The contact reacts temperature be 0-80 ℃, the reaction times is 8-36 hour.
9. according to claim 1 or 8 described methods, it is characterized in that 2-amino-6-propionamido-4,5,6,7-tetrahydro benzothiazol and NaBH
4And I
2Contact reacts be the mode of segmentation reaction, 0-35 ℃ of reaction 2-10 hour, 35-80 ℃ of reaction 8-24 hour.
10. according to claim 4 or 7 described methods, it is characterized in that described organic ethers is for containing C
4-C
10, O
1-O
2In the organic ether one or more are preferably ether.
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105753812A (en) * | 2016-03-28 | 2016-07-13 | 赤峰赛林泰药业有限公司 | Synthetic method for intermediate of pramipexoledihydrochloride |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005092871A2 (en) * | 2004-03-19 | 2005-10-06 | Dipharma S.P.A. | Intermediates for the preparation of pramipexole |
CN101585818A (en) * | 2009-06-08 | 2009-11-25 | 上海医药工业研究院 | A kind of preparation method who is used to prepare intermediate body of pramipexole dihydrochloride |
CN101676272A (en) * | 2008-09-17 | 2010-03-24 | 北京德众万全药物技术开发有限公司 | preparation method of pramipexole |
-
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005092871A2 (en) * | 2004-03-19 | 2005-10-06 | Dipharma S.P.A. | Intermediates for the preparation of pramipexole |
CN101676272A (en) * | 2008-09-17 | 2010-03-24 | 北京德众万全药物技术开发有限公司 | preparation method of pramipexole |
CN101585818A (en) * | 2009-06-08 | 2009-11-25 | 上海医药工业研究院 | A kind of preparation method who is used to prepare intermediate body of pramipexole dihydrochloride |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105753812A (en) * | 2016-03-28 | 2016-07-13 | 赤峰赛林泰药业有限公司 | Synthetic method for intermediate of pramipexoledihydrochloride |
CN105753812B (en) * | 2016-03-28 | 2017-12-08 | 赤峰赛林泰药业有限公司 | The synthetic method of body of Pramipexole dihydrochloride intermediate |
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