CN103435555B - Preparation method of 4-chloro-5-methylpyrimidine - Google Patents
Preparation method of 4-chloro-5-methylpyrimidine Download PDFInfo
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- CN103435555B CN103435555B CN201310376770.1A CN201310376770A CN103435555B CN 103435555 B CN103435555 B CN 103435555B CN 201310376770 A CN201310376770 A CN 201310376770A CN 103435555 B CN103435555 B CN 103435555B
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- methylpyrimidine
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- hydrazinopyrimidine
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- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- RPDVPWWBNQKLAS-UHFFFAOYSA-N 4-chloro-5-methylpyrimidine Chemical compound CC1=CN=CN=C1Cl RPDVPWWBNQKLAS-UHFFFAOYSA-N 0.000 title abstract description 12
- 238000006243 chemical reaction Methods 0.000 claims abstract description 37
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 26
- 238000003756 stirring Methods 0.000 claims abstract description 21
- 239000002904 solvent Substances 0.000 claims abstract description 17
- 239000012153 distilled water Substances 0.000 claims abstract description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000012065 filter cake Substances 0.000 claims abstract description 13
- 239000003208 petroleum Substances 0.000 claims abstract description 13
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 claims abstract description 10
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims abstract description 10
- 238000001035 drying Methods 0.000 claims abstract description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims abstract description 7
- 238000001816 cooling Methods 0.000 claims abstract description 7
- 238000001514 detection method Methods 0.000 claims abstract description 7
- 239000000706 filtrate Substances 0.000 claims abstract description 7
- 238000004809 thin layer chromatography Methods 0.000 claims abstract description 7
- 238000004140 cleaning Methods 0.000 claims abstract description 6
- 239000000047 product Substances 0.000 claims abstract description 6
- APRMCBSTMFKLEI-UHFFFAOYSA-N 2-chloro-5-methylpyrimidine Chemical compound CC1=CN=C(Cl)N=C1 APRMCBSTMFKLEI-UHFFFAOYSA-N 0.000 claims description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- 230000015572 biosynthetic process Effects 0.000 claims description 17
- 238000003786 synthesis reaction Methods 0.000 claims description 17
- 238000000967 suction filtration Methods 0.000 claims description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 239000002244 precipitate Substances 0.000 claims description 8
- 230000006837 decompression Effects 0.000 claims description 6
- 238000010792 warming Methods 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 3
- 239000000284 extract Substances 0.000 claims description 2
- 238000000605 extraction Methods 0.000 claims description 2
- OCQKKFDHCVWZFF-UHFFFAOYSA-N (6-chloro-5-methylpyrimidin-4-yl)hydrazine Chemical compound CC1=C(Cl)N=CN=C1NN OCQKKFDHCVWZFF-UHFFFAOYSA-N 0.000 abstract description 6
- NUEYDUKUIXVKNB-UHFFFAOYSA-N 4,6-dichloro-5-methylpyrimidine Chemical compound CC1=C(Cl)N=CN=C1Cl NUEYDUKUIXVKNB-UHFFFAOYSA-N 0.000 abstract description 5
- 238000005406 washing Methods 0.000 abstract description 5
- 238000001914 filtration Methods 0.000 abstract 2
- UKWHYYKOEPRTIC-UHFFFAOYSA-N mercury(ii) oxide Chemical compound [Hg]=O UKWHYYKOEPRTIC-UHFFFAOYSA-N 0.000 abstract 2
- 238000001704 evaporation Methods 0.000 abstract 1
- 238000010438 heat treatment Methods 0.000 abstract 1
- 229940101209 mercuric oxide Drugs 0.000 abstract 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 239000000126 substance Substances 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
- 229910000564 Raney nickel Inorganic materials 0.000 description 4
- 238000002386 leaching Methods 0.000 description 4
- 238000004949 mass spectrometry Methods 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010040880 Skin irritation Diseases 0.000 description 1
- 108010062740 TRPV Cation Channels Proteins 0.000 description 1
- 102000003566 TRPV1 Human genes 0.000 description 1
- 102100029613 Transient receptor potential cation channel subfamily V member 1 Human genes 0.000 description 1
- 101150016206 Trpv1 gene Proteins 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 229940049706 benzodiazepine Drugs 0.000 description 1
- 239000007806 chemical reaction intermediate Substances 0.000 description 1
- 238000010960 commercial process Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000036556 skin irritation Effects 0.000 description 1
- 231100000475 skin irritation Toxicity 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The invention discloses a preparation method of 4-chloro-5-methylpyrimidine. The preparation method comprises the following steps of: adding an A solvent to a reactor, stirring at room temperature and slowly adding hydrazine hydrate, uniformly stirring and adding 4,6-dichloro-5-methylpyrimidine which is 0.85-0.92 time as much as the mass of the hydrazine hydrate, heating to 60-80 DEG C until a thin-layer chromatography detection reaction is complete, cooling, filtering, cleaning a filter cake through 150-180 parts of distilled water by mass, and drying the filter cake to be constant in weight to obtain 4-chloro-5-methyl-6-hydrazinopyrimidine; adding a B solvent to the reactor, adding distilled water and 4-chloro-5-methyl-6-hydrazinopyrimidine, adding mercuric oxide which is 2.2-2.8 times as much as the mass of the 4-chloro-5-methyl-6-hydrazinopyrimidine while stirring, reacting for 30-40min at 20-60 DEG C, filtering, washing a filter cake through petroleum ether, extracting filtrate through petroleum ether, drying a petroleum ether layer through anhydrous sodium sulfate, and decompressing and evaporating to obtain a solvent which is product 4-chloro-5-methylpyrimidine. The preparation method is short in step, high in product yield, simple to operate, low in cost, safe and environment-friendly.
Description
Technical field
The invention belongs to technical field of chemistry, relate to the preparation method of the chloro-5-methylpyrimidine of a kind of 4-.
Background technology
4-chloro-5-methylpyrimidine is intermediate important in pharmaceutical synthesis, can be applicable to the synthesis of benzodiazepine, the synthesis of capsaicin receptor (VR1) and the synthesis of TRPV1.The chloro-5-methylpyrimidine of current 4-preparation method, relevant reported literature is as follows:
" organic chemistry " (1984,49(2): 296-300, David. Ke Fen (David L. Coffen)) synthetic route of disclosed 4-chloro-5-methylpyrimidine is as follows:
The operational path reactions steps of this synthesis 4-chloro-5-methylpyrimidine is longer, and each step of reaction needs more reactions steps, and operation is comparatively complicated.
PCT Int.Appl., 2010041054,2010, McDonald(Madonna), Edward(Edward) etc. the operational path of people disclosed preparation 4-chloro-5-methylpyrimidine as follows:
Its operational path reactions steps preparing 4-chloro-5-methylpyrimidine is more, and operation is comparatively complicated, and needs reflux operation 16 hours, and efficiency is lower.Employ Raney's nickel in reaction as catalyzer, the Raney's nickel participated in after reaction still containing a large amount of hydrogen, should may be destroyed in ventilation, can produce obnoxious flavour during Raney's nickel burning; Direct contact Raney's nickel may cause respiratory inflammation, also can cause the infringement of eyes and skin irritation, and suction can cause the fibrosis of nasal cavity and lung, larger to the injury of human body.
Summary of the invention
The object of the invention is to overcome above-mentioned shortcoming and a kind of reactions steps provided is short, product yield is high, simple to operate, cost is low and the preparation method of the chloro-5-methylpyrimidine of the 4-of safety and environmental protection.
The preparation method of the chloro-5-methylpyrimidine of a kind of 4-of the present invention, comprises the steps:
(1) synthesis of the chloro-5-methyl of 4--6-hydrazinopyrimidine
A solvent 82 ~ 105 mass parts is added in reactor, hydrazine hydrate 60 mass parts is added under stirring at room temperature, 4 of hydrazine hydrate quality 0.85 ~ 0.92 times amount are added again after stirring, the chloro-5-methylpyrimidine of 6-bis-, is warming up to 60 DEG C ~ 80 DEG C reactions complete to thin-layer chromatography detection reaction, cooling, suction filtration, filter cake distilled water cleans, and dries to constant weight, obtains the chloro-5-methyl of 4--6-hydrazinopyrimidine;
(2) synthesis of the chloro-5-methylpyrimidine of 4-
B solvent 78 ~ 119 mass parts is added in reactor, add 100 ~ 150 mass parts distilled water and the chloro-5-methyl of 4--6-hydrazinopyrimidine 50 mass parts again, the red precipitate adding the chloro-5-methyl of 4--6-hydrazinopyrimidine quality 2.2 ~ 2.8 times amount under stirring reacts, temperature of reaction controls at 20 ~ 60 DEG C, react 30 ~ 40 minutes, suction filtration, with the petroleum ether filter cake of 100 ~ 200 mass parts, gained filtrate uses the Petroleum ether extraction of 150 ~ 220 mass parts again, use anhydrous sodium sulfate drying petroleum ether layer, decompression steams solvent, obtains the chloro-5-methylpyrimidine of product 4-.
A solvent is Virahol, or methyl alcohol: the same volume mixing solutions of Virahol.
B solvent is methyl alcohol, ethanol or Virahol.
The preparation method of the chloro-5-methylpyrimidine of above-mentioned a kind of 4-, wherein: the distilled water consumption cleaning filter cake in (1) step is 150 ~ 180 mass parts.
The preparation method of the chloro-5-methylpyrimidine of above-mentioned a kind of 4-, wherein: sherwood oil extracts at twice.
The present invention compared with prior art, has obvious beneficial effect, as can be known from the above technical solutions: the preparation method of the chloro-5-methylpyrimidine of a kind of 4-of the present invention, with 4, the chloro-5-methylpyrimidine of 6-bis-is raw material, and obtain the chloro-5-methylpyrimidine of 4-through reduction, replacement, chemical equation is as follows:
Ⅲ Ⅱ Ⅰ
The reaction that 4-chloro-5-methyl-6-hydrazinopyrimidine (II) prepares the chloro-5-methylpyrimidine (I) of 4-need be carried out under the effect of red precipitate, red precipitate to be held concurrently oxygenant as the catalyzer of reaction, while quickening reaction process, control reaction conditions preferably, the temperature of reaction is controlled between 20 DEG C ~ 60 DEG C.The temperature of reaction that the chloro-5-methylpyrimidine (III) of reaction intermediate 4,6-bis-prepares the chloro-5-methyl of 4--6-hydrazinopyrimidine controls at 60 DEG C ~ 80 DEG C.Present method product average yield can reach 87%, it is short that method has reactions steps, simple to operate beneficial effect of Denging, can be applicable in commercial process.
The specific embodiment of the present invention is provided in detail by following examples.
Embodiment
Describe the present invention below in conjunction with example, explain and illustrate technical scheme feature of the present invention further.
embodiment 1
(1) synthesis of the chloro-5-methyl of 4--6-hydrazinopyrimidine
The mixing solutions 82g that methyl alcohol and Virahol are prepared by equal volume is added in reactor, 60g hydrazine hydrate is added under stirring at room temperature, add 4,6-bis-chloro-5-methylpyrimidine 51g after stirring again, be warming up to 60 DEG C of reactions complete to thin-layer chromatography detection reaction, cooling, suction filtration, filter cake 150g distilled water cleans to colourless, dries to constant weight, obtain the chloro-5-methyl of white solid 4--6-hydrazinopyrimidine 46.89g, productive rate is 94.5%.
(2) synthesis of the chloro-5-methylpyrimidine of 4-
94.7g ethanol is added in reactor, and the chloro-5-methyl of the 4--6-hydrazinopyrimidine 50g of gained in 120g distilled water and (1) is joined in reactor, 110g red precipitate is added under stirring, temperature of reaction controls at 20 DEG C, react 40 minutes, terminate reaction, suction filtration goes out suspended substance, washing leaching cake is carried out with 100g sherwood oil, filtrate is extracted at twice with 150g sherwood oil again, uses anhydrous sodium sulfate drying petroleum ether layer, and decompression steams solvent, obtain light yellow solid 4-chloro-5-methylpyrimidine 32.95g, this step productive rate is 81.3%.
1HNMR(400MHz,DMSO-d6)δ2.41(s,3H),8.70(s,1H),9.30(s,1H)；
Mass spec 129(M+).
embodiment 2
A preparation method for the chloro-5-methylpyrimidine of 4-, comprises the steps:
(1) synthesis of the chloro-5-methyl of 4--6-hydrazinopyrimidine
82g Virahol is added in reactor, 60g hydrazine hydrate is added under stirring at room temperature, add 4,6-bis-chloro-5-methylpyrimidine 53.4g after stirring again, be warming up to 70 DEG C of reactions complete to thin-layer chromatography detection reaction, cooling, suction filtration, the cleaning of filter cake 175g distilled water, to colourless, is dried to constant weight, obtain the chloro-5-methyl of white solid 4--6-hydrazinopyrimidine 50.55g, productive rate is 97.3%.
(2) synthesis of the chloro-5-methylpyrimidine of 4-
119g ethanol is added in reactor, the chloro-5-methyl of the 4--6-hydrazinopyrimidine 50g of gained in 150g distilled water and (1) is joined in reactor, 110g red precipitate is added under stirring, temperature of reaction controls at 40 DEG C, react 35 minutes, terminate reaction, suction filtration goes out suspended substance, washing leaching cake is carried out with 150g sherwood oil, filtrate is extracted at twice with 180g sherwood oil again, and use anhydrous sodium sulfate drying petroleum ether layer, decompression steams solvent, obtain light yellow solid 4-chloro-5-methylpyrimidine 34.53g, this step productive rate is 85.2%.
1HNMR(400MHz,DMSO-d6)δ2.41(s,3H),8.70(s,1H),9.30(s,1H)；
Mass spec 129(M+).
embodiment 3
A preparation method for the chloro-5-methylpyrimidine of 4-, comprises the steps:
(1) synthesis of the chloro-5-methyl of 4--6-hydrazinopyrimidine
105g Virahol is added in reactor, 60g hydrazine hydrate is added under stirring at room temperature, add 4,6-bis-chloro-5-methylpyrimidine 54g after stirring again, be warming up to 80 DEG C of reactions complete to thin-layer chromatography detection reaction, cooling, suction filtration, the cleaning of filter cake 180g distilled water, to colourless, is dried to constant weight, obtain the chloro-5-methyl of white solid 4--6-hydrazinopyrimidine 52.12g, productive rate is 99.2%.
(2) synthesis of the chloro-5-methylpyrimidine of 4-
119g methyl alcohol is added in reactor, the chloro-5-methyl of the 4--6-hydrazinopyrimidine 50g of gained in 150g distilled water and (1) is joined in reactor, 135g red precipitate is added under stirring, temperature of reaction controls at 60 DEG C, react 30 minutes, terminate reaction, suction filtration goes out suspended substance, washing leaching cake is carried out with 200g sherwood oil, filtrate is extracted at twice with 150g sherwood oil again, uses anhydrous sodium sulfate drying petroleum ether layer, and decompression steams solvent, obtain light yellow solid 4-chloro-5-methylpyrimidine 37.09g, this step productive rate is 91.5%.
1HNMR(400MHz,DMSO-d6)δ2.41(s,3H),8.70(s,1H),9.30(s,1H)；
Mass spec 129(M+).
embodiment 4
A preparation method for the chloro-5-methylpyrimidine of 4-, comprises the steps:
(1) synthesis of the chloro-5-methyl of 4--6-hydrazinopyrimidine
105g Virahol is added in reactor, 60g hydrazine hydrate is added under stirring at room temperature, add 4,6-bis-chloro-5-methylpyrimidine 55.2g after stirring again, be warming up to 80 DEG C of reactions complete to thin-layer chromatography detection reaction, cooling, suction filtration, the cleaning of filter cake 180g distilled water, to colourless, is dried to constant weight, obtain the chloro-5-methyl of white solid 4--6-hydrazinopyrimidine 51.77g, productive rate is 96.4%.
(2) synthesis of the chloro-5-methylpyrimidine of 4-
78g Virahol is added in reactor, the chloro-5-methyl of the 4--6-hydrazinopyrimidine 50g of gained in 100g distilled water and (1) is joined in reactor, 140g red precipitate is added under stirring, temperature of reaction controls at 60 DEG C, react 40 minutes, terminate reaction, suction filtration goes out suspended substance, washing leaching cake is carried out with 100g sherwood oil, filtrate is extracted at twice with 220g sherwood oil again, uses anhydrous sodium sulfate drying petroleum ether layer, and decompression steams solvent, obtain light yellow solid 4-chloro-5-methylpyrimidine 35.95g, this step productive rate is 88.7%.
1HNMR(400MHz,DMSO-d6)δ2.41(s,3H),8.70(s,1H),9.30(s,1H);
Mass spec 129(M+).
the above, it is only preferred embodiment of the present invention, not any pro forma restriction is done to the present invention, anyly do not depart from technical solution of the present invention content, the any simple modification done above embodiment according to technical spirit of the present invention, equivalent variations and modification, all still belong in the scope of technical solution of the present invention.
Claims (3)
1. a preparation method for the chloro-5-methylpyrimidine of 4-, comprises the steps:
(1) synthesis of the chloro-5-methyl of 4--6-hydrazinopyrimidine
A solvent 82 ~ 105 mass parts is added in reactor, hydrazine hydrate 60 mass parts is added under stirring at room temperature, 4 of hydrazine hydrate quality 0.85 ~ 0.92 times amount are added again after stirring, the chloro-5-methylpyrimidine of 6-bis-, is warming up to 60 DEG C ~ 80 DEG C reactions complete to thin-layer chromatography detection reaction, cooling, suction filtration, filter cake distilled water cleans, and dries to constant weight, obtains the chloro-5-methyl of 4--6-hydrazinopyrimidine;
(2) synthesis of the chloro-5-methylpyrimidine of 4-
B solvent 78 ~ 119 mass parts is added in reactor; add 100 ~ 150 mass parts distilled water and the chloro-5-methyl of 4--6-hydrazinopyrimidine 50 mass parts again; the red precipitate adding the chloro-5-methyl of 4--6-hydrazinopyrimidine quality 2.2 ~ 2.8 times amount under stirring reacts; temperature of reaction controls at 20 ~ 60 DEG C; react 30 ~ 40 minutes; suction filtration; with the petroleum ether filter cake of 100 ~ 200 mass parts; gained filtrate uses the Petroleum ether extraction of 150 ~ 220 mass parts again; use anhydrous sodium sulfate drying petroleum ether layer; decompression steams solvent, obtains the chloro-5-methylpyrimidine of product 4-;
A solvent is Virahol, or methyl alcohol: the same volume mixing solutions of Virahol;
B solvent is methyl alcohol, ethanol or Virahol.
2. the preparation method of the chloro-5-methylpyrimidine of a kind of 4-as claimed in claim 1, wherein: the distilled water consumption cleaning filter cake in (1) step is 150 ~ 180 mass parts.
3. the preparation method of the chloro-5-methylpyrimidine of a kind of 4-as claimed in claim 1 or 2, wherein: sherwood oil extracts at twice.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB854011A (en) * | 1958-09-10 | 1960-11-16 | Ici Ltd | New pyrimidines |
| WO1993018011A1 (en) * | 1992-03-06 | 1993-09-16 | Dowelanco | Process for the preparation of 2-alkylthio-4-hydrazino-5-fluoropyrimidines |
| JP2010077066A (en) * | 2008-09-25 | 2010-04-08 | Fujifilm Corp | Method for producing 5-aminopyrazole derivative |
| CN102171202A (en) * | 2008-10-06 | 2011-08-31 | 癌症研究技术有限公司 | Pyridine and pyrimidine based compounds as WNT signaling pathway inhibitors for the treatment of cancer |
-
2013
- 2013-08-27 CN CN201310376770.1A patent/CN103435555B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB854011A (en) * | 1958-09-10 | 1960-11-16 | Ici Ltd | New pyrimidines |
| WO1993018011A1 (en) * | 1992-03-06 | 1993-09-16 | Dowelanco | Process for the preparation of 2-alkylthio-4-hydrazino-5-fluoropyrimidines |
| JP2010077066A (en) * | 2008-09-25 | 2010-04-08 | Fujifilm Corp | Method for producing 5-aminopyrazole derivative |
| CN102171202A (en) * | 2008-10-06 | 2011-08-31 | 癌症研究技术有限公司 | Pyridine and pyrimidine based compounds as WNT signaling pathway inhibitors for the treatment of cancer |
Non-Patent Citations (2)
| Title |
|---|
| 2-烃基喹噁啉的合成;袁国淦等;《南京大学学报(自然科学版)》;19821231(第3期);669-677 * |
| 3-氯-5-甲基哒嗪的合成研究;赵春深等;《化学试剂》;20091231;第31卷(第10期);819-850 * |
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Denomination of invention: A preparation method of 4-chloro-5-methylpyrimidine Effective date of registration: 20211103 Granted publication date: 20150624 Pledgee: Guiyang Jinyang sub branch of China Construction Bank Co.,Ltd. Pledgor: GUIZHOU WYLTON JINGLIN ELECTRONIC MATERIAL CO.,LTD. Registration number: Y2021520000016 |
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