CN102558059A - Brand-new indazole compound and its synthetic method - Google Patents
Brand-new indazole compound and its synthetic method Download PDFInfo
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- CN102558059A CN102558059A CN2011102423882A CN201110242388A CN102558059A CN 102558059 A CN102558059 A CN 102558059A CN 2011102423882 A CN2011102423882 A CN 2011102423882A CN 201110242388 A CN201110242388 A CN 201110242388A CN 102558059 A CN102558059 A CN 102558059A
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Abstract
The invention provides a brand-new indazole compound, namely 5-bromo-4-(trifluoromethyl)indole. Its synthetic method is to use 2-methyl-3-nitrobenzotrifluoride as a starting raw material to prepare the target compound indazole derivative which has physiological activity of resisting arthritis, tumor, vomiting and the like. The indazole compound has a very wide application prospect from the medical angle or the agricultural angle. The synthesized indazole compound, which is not only a multifunctional compound but also a fluorine-containing medical intermediate, will be highly concerned in the field of novel drug research and development.
Description
Technical field
The present invention relates to a kind of new indazole compounds and compound method thereof, be specially invention of bromination trifluoromethyl indazole and compound method thereof.
Background technology
Indazole compounds extensively is present in the natural product and drug molecule of biologically active, is important medicine intermediate.Fluoridizing indazole compounds is one type of chemical medicine midbody that show great attention in current new drug development field.Because its good pharmacologically active and potential pharmaceutical use, the synthetic of indazole derivatives receives much attention.My company relies on the scientific research advantage, takes the lead in succeeding in developing.Do parent with this compound and can further synthesize more complicated verivate, condition is provided for studying such compound property more widely.
Summary of the invention
The present invention aims to provide a kind of brand-new indazole compounds and compound method thereof, and this method is simple relatively, raw material is easy to get.
A kind of brand-new indazole compounds provided by the invention is a 5-bromo-4-trifluoromethyl indazole, its structural formula:
A kind of brand-new indazole compounds provided by the invention and compound method thereof comprise the steps:
(1). 2-methyl-3-nitro trifluoromethylbenzene is used hydrogen reducing.
(2). with the reduzate bromination.
(3). close ring with Isopentyl nitrite, obtain the finished product.
Reaction equation:
Two emphasis are arranged in this highway route design, in one step of first bromination, before closing ring, can well be located product; It two is to use the effect of Sodium Nitrite more far short of what is expected than this design in Guan Huanyi step.
Description of drawings
Fig. 1 is the HNMR collection of illustrative plates of 5-bromo-4-trifluoromethyl indazole.
Embodiment
One. 10 gram 2-methyl-3-nitro trifluoromethylbenzenes are dissolved in 70 ml methanol; Under the nitrogen protection, 5 gram palladium carbon are added above-mentioned solution, hydrogen exchange 3 times.Stirred overnight under the room temperature.Filter, filtrating is revolved dried, gets solid phase prod A2.6g, productive rate 30.37%.TLC information (PE: EA=5: 1): raw material Rf=0.69, product Rf=0.30.
Two. 0.5 gram A is dissolved in 22ml acetic acid, refluxes, in mixed solution, drip the acetum that 4.77 gram bromines are dissolved in 15 milliliters.Stirred 2 hours, and reacted completely.Reaction solution is poured in the frozen water, transferred PH8～9 with saturated sodium bicarbonate, ethyl acetate extraction is crossed column purification.Get product B 3.2 grams, productive rate 39.4%.1H-NMR(CDCl3；400MHZ)：7.382(d，1H)；6.920(d，1H)
Three. B is dissolved in the 500ml chloroform, the ice bath cooling, with 2.65 gram Potassium ethanoates, 2.65 gram diacetyl oxides add in the above-mentioned solution successively, and deicing is bathed after 5 minutes, returns to room temperature naturally, after 1 hour, reacts completely.Add 3.35 gram Isopentyl nitrites, 0.69 gram hexaoxacyclooctadecane-6-6, reflux is spent the night.
React completely, it is imitative to revolve dechlorination, adds H
2O: EA=1: 1 (300ml) be its dissolving, EA aqueous phase extracted three times, and anhydrous magnesium sulfate drying adds 324 milliliters of MeOH and 45.81 gram salt of wormwood in bullion, and TLC detects to supreme ethanoyl product.System is concentrated, cross post and obtain product.Get product 1.95G, productive rate 55.36%.1H-NMR(CDCl3；400MHZ)：8.325(S，1H)；7.645(d，1H)；7.379(d，1H)。
Claims (2)
1. indazole compounds, name is called 5-bromo-4-trifluoromethyl indazole, and its structural formula is:
2. the compound method of indazole compounds as claimed in claim 1 is characterized in that, comprises the steps:
(1). under the nitrogen protection, 2-methyl-3-nitro trifluoromethylbenzene is reduced stirred overnight under the room temperature with hydrogen (palladium carbon).Filter, filtrating is revolved dried, gets solid phase prod;
(2). with the reduzate bromination.Stirred 2 hours, and reacted completely, under the low temperature, transfer PH=8～9 with saturated sodium bicarbonate, ethyl acetate extraction, purifying gets product;
(3). will go up the step product and protect with diacetyl oxide, Isopentyl nitrite closes ring, uses the salt of wormwood hydrolysis, and purifying obtains the finished product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN2011102423882A CN102558059A (en) | 2011-08-23 | 2011-08-23 | Brand-new indazole compound and its synthetic method |
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| Application Number | Priority Date | Filing Date | Title |
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| CN2011102423882A CN102558059A (en) | 2011-08-23 | 2011-08-23 | Brand-new indazole compound and its synthetic method |
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| CN102558059A true CN102558059A (en) | 2012-07-11 |
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| CN2011102423882A Pending CN102558059A (en) | 2011-08-23 | 2011-08-23 | Brand-new indazole compound and its synthetic method |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105726532A (en) * | 2016-02-03 | 2016-07-06 | 张少峰 | Simvastatin composition and application thereof in preparation of medicine for treating osteoporotic fracture |
| CN108911989A (en) * | 2018-08-15 | 2018-11-30 | 济南悟通生物科技有限公司 | A kind of synthetic method of 2- methyl-3-trifluoromethyl phenylamine |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011072488A1 (en) * | 2009-12-18 | 2011-06-23 | Glaxo Group Limited | Oxadiazole substituted indazole derivatives for use as sphingosine 1-phosphate 1 (s1p1) receptor agonists |
-
2011
- 2011-08-23 CN CN2011102423882A patent/CN102558059A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011072488A1 (en) * | 2009-12-18 | 2011-06-23 | Glaxo Group Limited | Oxadiazole substituted indazole derivatives for use as sphingosine 1-phosphate 1 (s1p1) receptor agonists |
Non-Patent Citations (1)
| Title |
|---|
| CARMEN MAIEREANU ET AL: "A novel amino-benzosuberone derivative is a picomolar inhibitor of mammalian aminopeptidase N/CD13", 《BIOORGANIC & MEDICINAL CHEMISTRY》, vol. 19, 19 July 2011 (2011-07-19), pages 5716 - 5733, XP028389436, DOI: doi:10.1016/j.bmc.2011.06.089 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105726532A (en) * | 2016-02-03 | 2016-07-06 | 张少峰 | Simvastatin composition and application thereof in preparation of medicine for treating osteoporotic fracture |
| CN108911989A (en) * | 2018-08-15 | 2018-11-30 | 济南悟通生物科技有限公司 | A kind of synthetic method of 2- methyl-3-trifluoromethyl phenylamine |
| CN108911989B (en) * | 2018-08-15 | 2020-11-03 | 济南悟通生物科技有限公司 | Synthesis method of 2-methyl-3-trifluoromethylaniline |
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Application publication date: 20120711 |