CN102250016A - Method for preparing 4,5,6-trichloropyrimidine - Google Patents
Method for preparing 4,5,6-trichloropyrimidine Download PDFInfo
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- CN102250016A CN102250016A CN2011101295800A CN201110129580A CN102250016A CN 102250016 A CN102250016 A CN 102250016A CN 2011101295800 A CN2011101295800 A CN 2011101295800A CN 201110129580 A CN201110129580 A CN 201110129580A CN 102250016 A CN102250016 A CN 102250016A
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Abstract
The invention discloses a method for preparing 4,5,6-trichloropyrimidine, and belongs to the technical field of chemical synthesis. The method comprises the following steps of: bromizing 4,6-dihydroxy pyrimidine serving as a raw material to obtain an intermediate 4,6-dihydroxy-5-bromopyrimidine, dissolving the intermediate in a solvent, and reacting with phosphorus oxychloride at the temperature of between 80 and 100DEG C for 4 to 18 hours in the presence of a catalyst to obtain reaction liquid; and cooling the reaction liquid to zero DEG C, regulating the pH value to be 6-7 by using 20 mass percent aqueous solution of sodium hydroxide, extracting for three times by using dichloromethane, washing the mixed extracting solution twice by using a saturated solution of ammonium chloride, washing twice by using a saturated saline solution, drying an organic phase by using anhydrous sodium sulfate, filtering, and concentrating to obtain the target compound of 4,5,6-trichloropyrimidine. The method has the advantages of simple and reasonable synthesis process, high conversion rate, practicable posttreatment, low production cost and the like.
Description
Technical field:
The present invention relates to a kind ofly 4,5, the preparation method of 6-trichloropyrimidine belongs to chemosynthesis technical field.
Background technology:
Pyrimidines is important intermediate, and they have important use in synthetic medicine and agricultural chemicals.
At present, according to document report for work mainly contain three kinds can be for reference route synthetic 4,5, the 6-trichloropyrimidine.But all come with some shortcomings.As document (Journal of the Chemical Society, 1955, p. 3478,3481) report is with 4, the 6-dihydroxy-pyrimidine is a starting raw material, after the iodine chloride chlorination, obtain intermediate 4,6-dihydroxyl-5-chloropyrimide, this intermediate react in the presence of Phosphorus Oxychloride and xylidine and obtain 4,5, the 6-trichloropyrimidine, the deficiency of this method is intermediate 4, and the yield of 6-dihydroxyl-5-chloropyrimide only is 40% for 52.0%(two steps total recovery only), and need to use iodine chloride to be chlorizating agent, raw materials cost is higher, is not suitable for amplifying producing.Document (EP2128141 A1 and for example, 2009) directly with 4, the 6-dihydroxy-pyrimidine is a starting raw material, with thionyl chloride and phosphorus oxychloride, make the chlorobenzene solution that alkali reacting by heating in chlorobenzene obtains target compound with triethylamine, it is the non-separation productive rate of 81%(that liquid phase is measured yield).The shortcoming of this method is to fail to obtain 4,5, the pure compound of 6-trichloropyrimidine, and also aftertreatment is comparatively loaded down with trivial details, is difficult to guarantee the quality of product.Document (EP1333029 A1,2003) is reported for work with 2, and the 4-dichloro pyrimidine is a raw material, obtains 4-chloro-6-hydroxy pyrimidine through hydrolysis, obtains 4 with sodium hypochlorite reaction then, and 5-two chloro-6-hydroxy pyrimidines are again at SOCl
2Effect under obtain final product, total recovery is 31.7%.This method steps is longer, has reduced production efficiency, is not suitable for suitability for industrialized production.The method (US6369259 B1,2002) that other has document to report for work has raw material (3,3-Dimethylaminobenzene nitrile) to be not easy to obtain again, and 4,5, the 6-trichloropyrimidine just generates with by product, the wretched insufficiency that productive rate is extremely low.
Based on the above-mentioned situation of prior art, the applicant makes the present invention.
Summary of the invention:
The object of the present invention is to provide a kind of synthesis technique simple, rationally, the transformation efficiency height, aftertreatment is feasible, production cost low 4,5, the preparation method of 6-trichloropyrimidine.
The technical scheme that the present invention takes is as follows, and is a kind of 4,5, and the preparation method of 6-trichloropyrimidine may further comprise the steps:
(1), with 4, the 6-dihydroxy-pyrimidine is a raw material, after bromination, obtain intermediate 4,6-dihydroxyl-5-bromo pyrimi piperidine, this intermediate is dissolved in the solvent, under catalyst, with Phosphorus Oxychloride under 80～100 ℃ of temperature, react 4 ~ 18 hours reaction solution, reaction finishes when liquid phase mass spectrometry detection reaction process, no raw material.
Describedly be used to dissolve intermediate 4, the solvent of 6-dihydroxyl-5-bromo pyrimi piperidine is selected from 1, a kind of in 2-ethylene dichloride, toluene, chloroform or the acetonitrile.The volume of solvent is 4,10 ~ 15 times of 6-dihydroxy-pyrimidine 5-bromo pyrimi piperidine.
Described catalyzer is a phase-transfer catalyst, be preferably benzyltriethylammoinium chloride or hexadecyl triethyl ammonium chloride, preferred especially benzyltriethylammoinium chloride, described 4,6-dihydroxy-pyrimidine 5-bromo pyrimi piperidine is 1:3.5 ~ 5.0 with the ratio of the amount of substance of benzyltriethylammoinium chloride.
Described 4,6-dihydroxy-pyrimidine 5-bromo pyrimi piperidine is 1:3.5 ~ 5.0 with the ratio of the amount of substance of Phosphorus Oxychloride.
(2), the reaction solution that obtains in the step 1 is cooled to zero degree, and be that 20% aqueous sodium hydroxide solution is regulated its pH value to 6 ~ 7 with mass concentration, use dichloromethane extraction then three times, the extraction liquid of merging washs secondary, saturated aqueous common salt washed twice with the ammonium chloride saturated solution, the organic phase anhydrous sodium sulfate drying, after the filtration, concentrate and obtain target compound 4,5, the 6-trichloropyrimidine, target compound obtains the high purity target compound through the petrol ether/ethyl acetate recrystallization.
The chemical equation that the present invention relates to is as follows:
。
Reaction principle of the present invention and beneficial effect are as follows:
Utilization of the present invention be simple and easy to 4, the 6-dihydroxy-pyrimidine is a raw material, after bromination, obtain intermediate 4,6-dihydroxyl-5-bromo pyrimi piperidine, this intermediate are in appropriate solvent, under the catalysis of benzyltriethylammoinium chloride, reacted 4 ~ 18 hours down for 80 to 100 ℃ in certain temperature with Phosphorus Oxychloride, obtain 4,5, the 6-trichloropyrimidine.The present invention compares with the above-mentioned existing synthetic method of reporting, major advantage is embodied in:
1, synthesis step is short, the technology advantages of simple, and good stability, production process safety, easy to operate, controllability is stronger;
2, used raw materials cost is easy to get, and aftertreatment is simple, and is environmentally friendly, and production cost is lower, process stabilizing;
3, transformation efficiency is higher, and the second step yield can reach more than 81%, and total recovery is more than 70%; The product purity height, HPLC〉99.18%.
The invention will be further described below in conjunction with the drawings and specific embodiments.
Description of drawings:
Fig. 1 is 4,5 of embodiment of the invention preparation, the 6-trichloropyrimidine (
1H NMR, 400M, solvent C DCl
3) nuclear magnetic resonance map;
Fig. 2 is 4,5 of embodiment of the invention preparation, the 6-trichloropyrimidine (
13C NMR, 400M, solvent C DCl
3) nuclear magnetic resonance map;
Fig. 3 is 4,5 of embodiment of the invention preparation, HPLC figure (the waters liquid chromatography 1525 of 6-trichloropyrimidine, chromatographic column: ZILIC 4.6mm*150mm*5um, moving phase is acetonitrile: water (volume ratio): trifluoroacetic acid=90:10:0.05, flow velocity: 0.800ML/min, wavelength 214nm).
Embodiment:
Embodiment 1:
In exsiccant 100 mL there-necked flasks, install reflux condensing tube additional, drop into 5.0 g 4,6-dihydroxyl-5-bromo pyrimi piperidine, 20.8 g benzyltriethylammoinium chlorides are dissolved in the 50 mL toluene, stir adding Phosphorus Oxychloride 14.0 g down, heat to 100 ℃ of reactions 18 hours.Reaction finishes when liquid phase mass spectrometry detection reaction process, no raw material.Reaction solution is cooled to zero degree then, and regulate its pH value to 6 ~ 7 with the aqueous solution of 20% sodium hydroxide, use dichloromethane extraction then three times, the extraction liquid that merges washs secondary, saturated aqueous common salt washed twice, organic phase anhydrous sodium sulfate drying with the ammonium chloride saturated solution, after the filtration, concentrate and obtain target compound 4,5,6-trichloropyrimidine.This compound obtains 3.76 g products through the petrol ether/ethyl acetate recrystallization, and yield is 78.3%, and HPLC 97.10%.
Embodiment 2:
In exsiccant 100 mL there-necked flasks, install reflux condensing tube additional, drop into 5.0 g 4,6-dihydroxyl-5-bromo pyrimi piperidine, 20.8 g benzyltriethylammoinium chlorides are dissolved in the 50 mL ethylene dichloride, stir adding Phosphorus Oxychloride 14.0 g down, heat to 80 ℃ of reactions 18 hours.Reaction finishes when liquid phase mass spectrometry detection reaction process, no raw material.Reaction solution is cooled to zero degree then, and regulate its pH value to 6 ~ 7 with the aqueous solution of 20% sodium hydroxide, use dichloromethane extraction then three times, the extraction liquid that merges washs secondary, saturated aqueous common salt washed twice, organic phase anhydrous sodium sulfate drying with the ammonium chloride saturated solution, after the filtration, concentrate and obtain target compound 4,5,6-trichloropyrimidine.This compound obtains 3.80 g products through the petrol ether/ethyl acetate recrystallization, and yield is 79.1%, and HPLC 97.80%.
Embodiment 3:
In exsiccant 100 mL there-necked flasks, install reflux condensing tube additional, drop into 5.0 g 4,6-dihydroxyl-5-bromo pyrimi piperidine, 20.8 g benzyltriethylammoinium chlorides are dissolved in the 50 mL acetonitriles, stir adding Phosphorus Oxychloride 14.0 g down, heat to 80 ℃ of reactions 18 hours.Reaction finishes when liquid phase mass spectrometry detection reaction process, no raw material.Reaction solution is cooled to zero degree then, and regulate its pH value to 6 ~ 7 with the aqueous solution of 20% sodium hydroxide, use dichloromethane extraction then three times, the extraction liquid that merges washs secondary, saturated aqueous common salt washed twice, organic phase anhydrous sodium sulfate drying with the ammonium chloride saturated solution, after the filtration, concentrate and obtain target compound 4,5,6-trichloropyrimidine.This compound obtains 3.85 g products through the petrol ether/ethyl acetate recrystallization, and yield is 80.10%, and HPLC 99.10%.
Embodiment 4:
In exsiccant 100 mL there-necked flasks, install reflux condensing tube additional, drop into 5.0 g 4,6-dihydroxyl-5-bromo pyrimi piperidine, 29.8 g benzyltriethylammoinium chlorides are dissolved in the 50 mL toluene, stir adding Phosphorus Oxychloride 14.0 g down, heat to 100 ℃ of reactions 5 hours.Reaction finishes when liquid phase mass spectrometry detection reaction process, no raw material.Reaction solution is cooled to zero degree then, and regulate its pH value to 6 ~ 7 with the aqueous solution of 20% sodium hydroxide, use dichloromethane extraction then three times, the extraction liquid that merges washs secondary, saturated aqueous common salt washed twice, organic phase anhydrous sodium sulfate drying with the ammonium chloride saturated solution, after the filtration, concentrate and obtain target compound 4,5,6-trichloropyrimidine.This compound obtains 3.65 g products through the petrol ether/ethyl acetate recrystallization, and yield is 76.10%, and HPLC 96.50%.
Embodiment 5:
In exsiccant 100 mL there-necked flasks, install reflux condensing tube additional, drop into 5.0 g 4,6-dihydroxyl-5-bromo pyrimi piperidine, 29.8 g benzyltriethylammoinium chlorides are dissolved in the 50 mL acetonitriles, stir adding Phosphorus Oxychloride 14.0 g down, heat to 80 ℃ of reactions 5 hours.Reaction finishes when liquid phase mass spectrometry detection reaction process, no raw material.Reaction solution is cooled to zero degree then, and regulate its pH value to 6 ~ 7 with the aqueous solution of 20% sodium hydroxide, use dichloromethane extraction then three times, the extraction liquid that merges washs secondary, saturated aqueous common salt washed twice, organic phase anhydrous sodium sulfate drying with the ammonium chloride saturated solution, after the filtration, concentrate and obtain target compound 4,5,6-trichloropyrimidine.This compound obtains 3.88 g products through the petrol ether/ethyl acetate recrystallization, and yield is 80.9%, and HPLC 98.40%.
Embodiment 6:
In exsiccant 100 mL there-necked flasks, install reflux condensing tube additional, drop into 5.0 g 4,6-dihydroxyl-5-bromo pyrimi piperidine, 29.8 g benzyltriethylammoinium chlorides are dissolved in the 50 mL ethylene dichloride, stir adding Phosphorus Oxychloride 14.0 g down, heat to 80 ℃ of reactions 5 hours.Reaction finishes when liquid phase mass spectrometry detection reaction process, no raw material.Reaction solution is cooled to zero degree then, and regulate its pH value to 6 ~ 7 with the aqueous solution of 20% sodium hydroxide, use dichloromethane extraction then three times, the extraction liquid that merges washs secondary, saturated aqueous common salt washed twice, organic phase anhydrous sodium sulfate drying with the ammonium chloride saturated solution, after the filtration, concentrate and obtain target compound 4,5,6-trichloropyrimidine.This compound obtains 3.72 g products through the petrol ether/ethyl acetate recrystallization, and yield is 77.6%, and HPLC 97.30%.
Embodiment 7:
In exsiccant 100 mL there-necked flasks, install reflux condensing tube additional, drop into 5.0 g 4,6-dihydroxyl-5-bromo pyrimi piperidine, 20.8 g benzyltriethylammoinium chlorides are dissolved in the 50 mL toluene, stir adding Phosphorus Oxychloride 20.0 g down, heat to 100 ℃ of reactions 18 hours.Reaction finishes when liquid phase mass spectrometry detection reaction process, no raw material.Reaction solution is cooled to zero degree then, and regulate its pH value to 6 ~ 7 with the aqueous solution of 20% sodium hydroxide, use dichloromethane extraction then three times, the extraction liquid that merges washs secondary, saturated aqueous common salt washed twice, organic phase anhydrous sodium sulfate drying with the ammonium chloride saturated solution, after the filtration, concentrate and obtain target compound 4,5,6-trichloropyrimidine.This compound obtains 3.89 g products through the petrol ether/ethyl acetate recrystallization, and yield is 81.0%, and HPLC 97.90%.
Embodiment 8:
In exsiccant 100 mL there-necked flasks, install reflux condensing tube additional, drop into 5.0 g 4,6-dihydroxyl-5-bromo pyrimi piperidine, 20.8 g benzyltriethylammoinium chlorides are dissolved in the 50 mL ethylene dichloride, stir adding Phosphorus Oxychloride 20.0 g down, heat to 80 ℃ of reactions 18 hours.Reaction finishes when liquid phase mass spectrometry detection reaction process, no raw material.Reaction solution is cooled to zero degree then, and regulate its pH value to 6 ~ 7 with the aqueous solution of 20% sodium hydroxide, use dichloromethane extraction then three times, the extraction liquid that merges washs secondary, saturated aqueous common salt washed twice, organic phase anhydrous sodium sulfate drying with the ammonium chloride saturated solution, after the filtration, concentrate and obtain target compound 4,5,6-trichloropyrimidine.This compound obtains 3.57 g products through the petrol ether/ethyl acetate recrystallization, and yield is 74.4%, and HPLC 95.50%.
Embodiment 9:
In exsiccant 100 mL there-necked flasks, install reflux condensing tube additional, drop into 5.0 g 4,6-dihydroxyl-5-bromo pyrimi piperidine, 20.8 g benzyltriethylammoinium chlorides are dissolved in the 50 mL acetonitriles, stir adding Phosphorus Oxychloride 20.0 g down, heat to 80 ℃ of reactions 18 hours.Reaction finishes when liquid phase mass spectrometry detection reaction process, no raw material.Reaction solution is cooled to zero degree then, and regulate its pH value to 6 ~ 7 with the aqueous solution of 20% sodium hydroxide, use dichloromethane extraction then three times, the extraction liquid that merges washs secondary, saturated aqueous common salt washed twice, organic phase anhydrous sodium sulfate drying with the ammonium chloride saturated solution, after the filtration, concentrate and obtain target compound 4,5,6-trichloropyrimidine.This compound obtains 3.80 g products through the petrol ether/ethyl acetate recrystallization, and yield is 79.3%, and HPLC 96.80%.
Product detects:
With the product 4,5 of embodiment 3 preparation, the 6-trichloropyrimidine carries out nuclear magnetic resonance map analysis and HPLC respectively and analyzes, as Fig. 1～shown in Figure 3, and Fig. 1
1Among the H NMR 8.681 (s, what 1H) show is single hydrogen on the pyrimidine ring; Fig. 2
13C NMR is shown as carbon atom peak, three groups of peaks of pyrimidine ring and is respectively 129,154,160; Fig. 3 is 4,5 of embodiment 3,6-trichloropyrimidine HPLC figure, and 2.088 is the retention time of target compound, purity is higher than 99%.
Claims (6)
1. one kind 4,5, the preparation method of 6-trichloropyrimidine is characterized in that, may further comprise the steps:
(1), with 4, the 6-dihydroxy-pyrimidine is a raw material, after bromination, obtain intermediate 4,6-dihydroxyl-5-bromo pyrimi piperidine, this intermediate is dissolved in the solvent, and solvent is selected from 1, a kind of in 2-ethylene dichloride, toluene, chloroform or the acetonitrile, the volume of solvent is 4,10 ~ 15 times of 6-dihydroxy-pyrimidine 5-bromo pyrimi piperidine; Under catalyst, with Phosphorus Oxychloride under 80～100 ℃ of temperature, react 4 ~ 18 hours reaction solution; Described catalyzer is benzyltriethylammoinium chloride or hexadecyl triethyl ammonium chloride; Described 4,6-dihydroxy-pyrimidine 5-bromo pyrimi piperidine is 1:3.5 ~ 5.0 with the ratio of the amount of substance of catalyzer; Described 4,6-dihydroxy-pyrimidine 5-bromo pyrimi piperidine is 1:3.5 ~ 5.0 with the ratio of the amount of substance of Phosphorus Oxychloride;
(2), the reaction solution that obtains in the step 1 is cooled to zero degree, with mass concentration is that 20% aqueous sodium hydroxide solution is regulated pH value to 6 ~ 7, use dichloromethane extraction then three times, the extraction liquid that merges ammonium chloride saturated solution washed twice, saturated aqueous common salt washed twice, organic phase anhydrous sodium sulfate drying, after the filtration, concentrate and obtain target compound 4,5,6-trichloropyrimidine.
2. according to claim described a kind of 4,5, the preparation method of 6-trichloropyrimidine is characterized in that: described catalyzer is a benzyltriethylammoinium chloride, 4,6-dihydroxy-pyrimidine 5-bromo pyrimi piperidine is 1:3.5 ~ 5.0 with the ratio of the amount of substance of benzyltriethylammoinium chloride.
3. described a kind of 4,5 according to claim, the preparation method of 6-trichloropyrimidine is characterized in that: the target compound 4,5 of step 2 preparation, the 6-trichloropyrimidine obtains high purity 4,5 through the petrol ether/ethyl acetate recrystallization, the 6-trichloropyrimidine.
4. according to claim described a kind of 4,5, the preparation method of 6-trichloropyrimidine is characterized in that: in exsiccant 100 mL there-necked flasks, install reflux condensing tube additional, drop into 5.0 g 4,6-dihydroxyl-5-bromo pyrimi piperidine, 20.8 g benzyltriethylammoinium chlorides are dissolved in the 50 mL acetonitriles, stir adding Phosphorus Oxychloride 14.0 g down, heat to 80 ℃ of reactions 18 hours; Reaction solution is cooled to zero degree then, the aqueous solution of the sodium hydroxide with 20% is regulated its pH value to 6 ~ 7, use dichloromethane extraction then three times, the extraction liquid that merges ammonium chloride saturated solution washed twice, saturated aqueous common salt washed twice, organic phase anhydrous sodium sulfate drying, after the filtration, concentrate and obtain target compound 4,5,6-trichloropyrimidine; Target compound obtains 3.85 g products through the petrol ether/ethyl acetate recrystallization, and yield is 80.10%, and HPLC 99.10%.
5. according to claim described a kind of 4,5, the preparation method of 6-trichloropyrimidine is characterized in that: in exsiccant 100 mL there-necked flasks, install reflux condensing tube additional, drop into 5.0 g 4,6-dihydroxyl-5-bromo pyrimi piperidine, 29.8 g benzyltriethylammoinium chlorides are dissolved in the 50 mL acetonitriles, stir adding Phosphorus Oxychloride 14.0 g down, heat to 80 ℃ of reactions 5 hours; Reaction solution is cooled to zero degree then, and the aqueous solution of the sodium hydroxide with 20% is regulated its pH value to 6 ~ 7, uses dichloromethane extraction then three times, the extraction liquid that merges washs secondary with the ammonium chloride saturated solution, the saturated aqueous common salt washed twice, the organic phase anhydrous sodium sulfate drying is after the filtration, concentrate and obtain target compound 4,5, the 6-trichloropyrimidine, target compound obtains 3.88 g products through the petrol ether/ethyl acetate recrystallization, yield is 80.9%, and HPLC 98.40%.
6. according to claim described a kind of 4,5, the preparation method of 6-trichloropyrimidine is characterized in that: in exsiccant 100 mL there-necked flasks, install reflux condensing tube additional, drop into 5.0 g 4,6-dihydroxyl-5-bromo pyrimi piperidine, 20.8 g benzyltriethylammoinium chlorides are dissolved in the 50 mL toluene, stir adding Phosphorus Oxychloride 20.0 g down, heat to 100 ℃ of reactions 18 hours; Reaction solution is cooled to zero degree then, and the aqueous solution of the sodium hydroxide with 20% is regulated its pH value to 6 ~ 7, uses dichloromethane extraction then three times, the extraction liquid that merges washs secondary with the ammonium chloride saturated solution, the saturated aqueous common salt washed twice, the organic phase anhydrous sodium sulfate drying is after the filtration, concentrate and obtain target compound 4,5, the 6-trichloropyrimidine, target compound obtains 3.89 g products through the petrol ether/ethyl acetate recrystallization, yield is 81.0%, and HPLC 97.90%.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110294715A (en) * | 2019-06-24 | 2019-10-01 | 南京普锐达医药科技有限公司 | Synthesis method of 2,4, 6-trichloro-5-methoxypyrimidine |
| CN114105865A (en) * | 2021-12-07 | 2022-03-01 | 江苏宝众宝达药业股份有限公司 | Synthesis process of 3,4, 5-trichloropyridine |
| CN114644594A (en) * | 2022-03-24 | 2022-06-21 | 郑州猫眼农业科技有限公司 | Preparation method of 5-bromo-2-chloropyrimidine |
| CN115490641A (en) * | 2022-10-17 | 2022-12-20 | 大连大学 | Synthesis method of 2-methyl-4, 5, 6-trichloropyrimidine |
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| US6369259B1 (en) * | 1996-06-10 | 2002-04-09 | Bayer Aktiengesellschaft | Method of preparing 4,5,6-trichloro-and 2,4,5,6-tetrachloropyrimidine |
| CN101646657A (en) * | 2007-03-28 | 2010-02-10 | 住友化学株式会社 | Process for producing trichloropyrimidine compound |
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2011
- 2011-05-19 CN CN2011101295800A patent/CN102250016B/en not_active Expired - Fee Related
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| US6369259B1 (en) * | 1996-06-10 | 2002-04-09 | Bayer Aktiengesellschaft | Method of preparing 4,5,6-trichloro-and 2,4,5,6-tetrachloropyrimidine |
| CN101646657A (en) * | 2007-03-28 | 2010-02-10 | 住友化学株式会社 | Process for producing trichloropyrimidine compound |
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| 《J. Org. Chem.》 19741231 Sujit Banerjee et al. Bromide Ion Induced Debromination of the 5,5-Dibromo Derivatives of "4,6-Dihydroxypyrimidine" and 6-Methyluracil 3120-3125 1-6 第39卷, 第21期 * |
| SUJIT BANERJEE ET AL.: "Bromide Ion Induced Debromination of the 5,5-Dibromo Derivatives of "4,6-Dihydroxypyrimidine" and 6-Methyluracil", 《J. ORG. CHEM.》 * |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110294715A (en) * | 2019-06-24 | 2019-10-01 | 南京普锐达医药科技有限公司 | Synthesis method of 2,4, 6-trichloro-5-methoxypyrimidine |
| CN110294715B (en) * | 2019-06-24 | 2022-05-13 | 南京普锐达医药科技有限公司 | Synthesis method of 2,4, 6-trichloro-5-methoxypyrimidine |
| CN114105865A (en) * | 2021-12-07 | 2022-03-01 | 江苏宝众宝达药业股份有限公司 | Synthesis process of 3,4, 5-trichloropyridine |
| CN114644594A (en) * | 2022-03-24 | 2022-06-21 | 郑州猫眼农业科技有限公司 | Preparation method of 5-bromo-2-chloropyrimidine |
| CN114644594B (en) * | 2022-03-24 | 2024-06-11 | 郑州猫眼农业科技有限公司 | Preparation method of 5-bromo-2-chloropyrimidine |
| CN115490641A (en) * | 2022-10-17 | 2022-12-20 | 大连大学 | Synthesis method of 2-methyl-4, 5, 6-trichloropyrimidine |
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