CN108794470B - 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine and synthesis method of downstream product thereof - Google Patents
6-hydrazino-1H-pyrazolo [3,4-b ] pyridine and synthesis method of downstream product thereof Download PDFInfo
- Publication number
- CN108794470B CN108794470B CN201810827151.2A CN201810827151A CN108794470B CN 108794470 B CN108794470 B CN 108794470B CN 201810827151 A CN201810827151 A CN 201810827151A CN 108794470 B CN108794470 B CN 108794470B
- Authority
- CN
- China
- Prior art keywords
- pyrazolo
- pyridine
- hydrazino
- compound
- bromo
- 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.)
- Active
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Abstract
The invention discloses a method for synthesizing 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine and downstream products thereof, relating to the technical field of synthesis of organic chemical intermediates; the synthesis method of 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine comprises the steps of firstly using cheap and easily-obtained 2, 6-dichloro-3-pyridinecarboxaldehyde and hydrazine hydrate as raw materials to obtain 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine, and then further using the 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine to synthesize a downstream product of the 6-bromo-1H-pyrazolo [3,4-b ] pyridine; the invention solves the problems of expensive raw materials and low yield of the 6-bromo-1H-pyrazolo [3,4-b ] pyridine prepared by the prior art, and the route has mild reaction conditions, simple subsequent operation and environmental friendliness, can prepare the product with higher yield and high purity, and is suitable for industrial process amplification.
Description
Technical Field
The invention relates to the technical field of synthesis of organic chemical intermediates, in particular to a synthesis method of 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine and a synthesis method for preparing 6-bromo-1H-pyrazolo [3,4-b ] pyridine.
Background
Indazoles, also known as benzopyrazoles or isoindolones, are aromatic compounds. In recent years, indazole derivatives have been found to possess a wide range of biological activities, such as anti-inflammatory, anti-HIV, anti-hypertensive, antimicrobial and anti-tumor activities. The indazole skeleton is applied to constructing various molecules or inhibitors with pharmaceutical activity, and has strong pharmacological significance. Drugs such as pazopanib, axitinib and nilapali containing an indazole backbone have been approved for the treatment of cancer. Related documents also report that indazole derivatives are applied to the treatment of diseases inhibiting protein kinases, and the like. Therefore, the indazole derivatives have potential medicinal value and wide market prospect.
The compound 6-bromo-1H-pyrazolo [3,4-b ] pyridine belongs to the azaindazole derivatives. Few reports are reported on the synthesis of 6-bromo-1H-pyrazolo [3,4-b ] pyridine, as shown in the following formula:
the method takes 3-aminopyrazole and methyl propiolate as raw materials to generate 1H-pyrazolo [3,4-b ] pyridine-6-alcohol in an acetic acid solvent; then carrying out reflux reaction with tribromooxyphosphorus to generate 6-bromo-1H-pyrazolo [3,4-b ] pyridine, wherein the yield of the two steps is 25%. In the post-treatment process, a large amount of waste liquid is generated due to the phosphorus oxybromide, so that the method is not environment-friendly and the treatment cost of the waste liquid is increased. And the second step of reaction requires column chromatography, so that industrial scale-up production is difficult to realize. Some other methods for synthesizing 6-bromo-1H-pyrazolo [3,4-b ] pyridine usually have expensive raw materials, require multi-step reaction, require extremely high temperature control on reaction conditions, and are inconvenient for industrial scale-up production.
Therefore, the research on developing a synthesis method which is environment-friendly and can efficiently synthesize the 6-bromo-1H-pyrazolo [3,4-b ] pyridine compound has important significance.
Disclosure of Invention
The invention aims to provide a method for synthesizing 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine, and a method for further synthesizing 6-bromo-1H-pyrazolo [3,4-b ] pyridine by using 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine, so as to solve the technical defects that in the prior art, the final product 6-bromo-1H-pyrazolo [3,4-b ] pyridine has low reaction yield and is not suitable for amplification.
In order to achieve the above purpose, the invention provides the following technical scheme:
a synthetic method of 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine comprises the following steps:
the specific synthesis steps are as follows: under the condition of room temperature, stirring the compound (1), 2, 6-dichloro-3-pyridinecarboxaldehyde and hydrazine hydrate in an organic solvent for reaction for 0.5-1H, heating to reflux overnight, cooling and filtering to obtain a compound (2), 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine; the amount of the organic solvent is at least such that the compound (1), 2, 6-dichloro-3-pyridinecarboxaldehyde, is completely dissolved.
Further, the compound (1) has a molar ratio of 2, 6-dichloro-3-pyridinecarboxaldehyde to hydrazine hydrate of 1 (4-6).
Further, the organic solvent includes one or more of n-butanol, t-butanol and DMF.
The invention also provides a downstream product based on the 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine synthesis method, which comprises 6-bromo-1H-pyrazolo [3,4-b ] pyridine.
The synthetic method of the 6-bromo-1H-pyrazolo [3,4-b ] pyridine comprises the following synthetic route:
the specific synthesis steps are as follows:
step 1) under the condition of room temperature, stirring a compound (1), namely 2, 6-dichloro-3-pyridinecarboxaldehyde, and hydrazine hydrate in an organic solvent for reaction for 0.5-1H, heating to reflux overnight, cooling and filtering to obtain a compound (2), namely 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine;
step 2) at room temperature, dissolving the compound (2) 6-hydrazino-1H-pyrazolo [3,4-B ] pyridine obtained in the step 1) in chloroform, then dropwise adding liquid bromine, keeping the temperature at 40 ℃, heating and refluxing for 1-6H after the liquid bromine is completely dropwise added, cooling to room temperature, and slowly dropwise adding saturated sodium bicarbonate solution in an ice bath to perform extraction and quenching reaction; dichloromethane is added for liquid separation and extraction, an organic layer is collected, dried and concentrated to obtain a yellow powdery solid compound (3), namely 6-bromo-1H-pyrazolo [3,4-B ] pyridine.
According to the technical scheme, the invention provides a method for synthesizing 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine and downstream products thereof, and the following beneficial effects are achieved:
1. the invention uses cheap and easily obtained 2, 6-dichloro-3-pyridinecarboxaldehyde and hydrazine hydrate as raw materials, firstly prepares the compound (2) 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine, provides a new method for preparing 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine, and has the advantages of high product yield, less by-products and environmental protection; then the compound (2) 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine reacts with liquid bromine to obtain a final product 6-bromo-1H-pyrazolo [3,4-b ] pyridine, and the yield of the two steps can reach more than 65%; the invention further solves the problems of expensive raw materials, low yield and strict reaction conditions in the prior art for synthesizing the 6-bromo-1H-pyrazolo [3,4-b ] pyridine, and the synthetic route has mild reaction conditions, is simple to operate, can prepare a product with higher yield and does not generate a large amount of waste liquid.
2. The invention provides a route for synthesizing 6-bromo-1H-pyrazolo [3,4-b ] pyridine, which has the advantages of simple synthesis steps, no complicated column chromatography, high yield of the product obtained by simple post-treatment extraction, filtration, drying and other simple steps, production cost saving, suitability for process amplification, simple and efficient preparation process and less by-products.
It should be understood that all combinations of the foregoing concepts and additional concepts described in greater detail below can be considered as part of the inventive subject matter of this disclosure unless such concepts are mutually inconsistent. The foregoing and other aspects, embodiments and features of the present teachings can be more fully understood from the following description taken in conjunction with the accompanying drawings. Additional aspects of the present invention, such as features and/or advantages of exemplary embodiments, will be apparent from the description which follows, or may be learned by practice of specific embodiments in accordance with the teachings of the present invention.
Drawings
The drawings are not intended to be drawn to scale. In the drawings, each identical or nearly identical component that is illustrated in various figures may be represented by a like numeral. For purposes of clarity, not every component may be labeled in every drawing. Embodiments of various aspects of the present invention will now be described, by way of example, with reference to the accompanying drawings, in which:
FIG. 1 is a hydrogen spectrum of an intermediate product of the synthetic route of the present invention, 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine;
FIG. 2 is a hydrogen spectrum of the final product of the synthetic route of the present invention, 6-bromo-1H-pyrazolo [3,4-b ] pyridine.
Detailed Description
In order to better understand the technical content of the present invention, specific embodiments are described below with reference to the accompanying drawings.
In this disclosure, aspects of the present invention are described with reference to the accompanying drawings, in which a number of illustrative embodiments are shown. Embodiments of the present disclosure are not necessarily intended to include all aspects of the invention. It should be appreciated that the various concepts and embodiments described above, as well as those described in greater detail below, may be implemented in any of numerous ways, as the disclosed concepts and embodiments are not limited to any one implementation. In addition, some aspects of the present disclosure may be used alone, or in any suitable combination with other aspects of the present disclosure.
Based on the problems that in the prior art, in the production and preparation process of a compound 6-bromo-1H-pyrazolo [3,4-b ] pyridine, the cost of raw material reactants is high, the yield of products in the synthesis step is low, the aftertreatment is complex, a large amount of waste liquid is generated, the environment is not friendly, the production cost is not suitable for industrial scale-up production, and the like, the invention aims to disclose a synthesis method of 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine, and the synthesis method obtained based on the 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine further reacts with other compounds to prepare the 6-bromo-1H-pyrazolo [3,4-b ] pyridine, the invention adopts reactants which are easy to obtain in the market and have low price, and the yield of products in the synthesis step is high, the synthesis method of the 6-bromo-1H-pyrazolo [3,4-b ] pyridine can also be used for industrial scale-up production.
The invention relates to a method for synthesizing 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine, under the condition of room temperature, the compound (1)2, 6-dichloro-3-pyridine formaldehyde and hydrazine hydrate are mixed in a molar ratio of 1: (4-6) stirring and reacting in an organic solvent for 0.5-1h, heating to reflux, standing overnight, cooling and filtering to obtain a solid product compound (2), namely 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine, wherein the organic solvent is one or more of n-butyl alcohol, tert-butyl alcohol and DMF, and the dosage of the organic solvent such as one or more of n-butyl alcohol, tert-butyl alcohol and DMF at least makes the compound (1), 2, 6-dichloro-3-pyridinecarboxaldehyde completely dissolved, and the specific synthetic route is as follows:
the invention also provides a downstream product of the 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine synthesis method, namely a synthesis method of 6-bromo-1H-pyrazolo [3,4-b ] pyridine, wherein the synthesis route is as follows:
the specific synthesis steps are as follows:
step 1) stirring a compound (1), namely 2, 6-dichloro-3-pyridinecarboxaldehyde and hydrazine hydrate in an organic solvent at a molar ratio of 1 (4-6) for 0.5-1H at room temperature, heating to reflux, standing overnight, cooling and filtering to obtain a solid product, namely compound (2), namely 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine;
step 2) at room temperature, dissolving the compound (2) 6-hydrazino-1H-pyrazolo [3,4-B ] pyridine obtained in the step 1) in chloroform, then dropwise adding liquid bromine, keeping the temperature at 40 ℃, heating and refluxing for 1-6H after the liquid bromine is completely dropwise added, cooling to room temperature, and slowly dropwise adding saturated sodium bicarbonate solution in an ice bath to perform extraction and quenching reaction; dichloromethane is added for liquid separation and extraction, an organic layer is collected, dried and concentrated to obtain a yellow powdery solid compound (3), namely, 6-bromo-1H-pyrazolo [3,4-B ] pyridine, wherein the chloroform can at least completely dissolve the compound (2), namely, 6-hydrazino-1H-pyrazolo [3,4-B ] pyridine.
The technical means of the present invention will be described below by way of specific examples, wherein the raw materials and reagents used in the present invention are commercially available.
In this document, "room temperature conditions" means a temperature range of 10 ℃ to 30 ℃ and DMF is N, N-dimethylformamide.
Example 1
Adding 2, 6-dichloro-3-pyridinecarboxaldehyde (1056g,6.0mol,1eq.) and hydrazine hydrate (1767g,30.0mol,5.0eq., 85%) into n-butanol, stirring at room temperature for 0.5H, then heating to reflux overnight, cooling, filtering, and collecting a filter cake, namely the compound (2) 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine (776g, 5.2mol), wherein the yield is 87%, and the product is white solid.
Taking a trace amount of compound (2) 6-hydrazino-1H-pyrazolo [3,4-b]Performing nuclear magnetic hydrogen spectrometry on pyridine, wherein the abscissa represents chemical shift, and the ordinate represents peak intensity, and combining with figure 1 to obtain compound (2) 6-hydrazino-1H-pyrazolo [3,4-b]The spectrum of the pyridine is shown in the specification,1H NMR(600MHz,DMSO)δ12.76(s,1H), 7.95(s,1H),7.81–7.60(m,2H),6.46(d,J=8.7Hz,1H),4.22(s,2H)。
further using the compound (2) 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine prepared above, the compound (3) 6-bromo-1H-pyrazolo [3,4-b ] pyridine is further prepared.
At room temperature, the compound (2), 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine (about 776g, 5.2mol, 1eq.) is dissolved in chloroform, liquid bromine (1662g, 10.4mol, 2.0eq.) is added dropwise, the temperature is kept at 40 ℃, the liquid bromine is added dropwise, heating and refluxing are carried out for 3H, after cooling to room temperature, saturated sodium bicarbonate solution is slowly added dropwise under the ice bath condition, and after the extraction reaction, dichloromethane is added, and liquid separation and extraction are carried out. The organic layer was collected, dried and concentrated to give a yellow powdery solid, giving compound (3) 6-bromo-1H-pyrazolo [3,4-b ] pyridine (772g, 3.9mol) in 75% yield, wherein the by-product was extracted for storage and impurity localization, and the waste stream was further recycled.
Taking micro 50mg of compound (3) to perform nuclear magnetic hydrogen spectrum measurement, wherein the abscissa represents chemical shift, the ordinate represents peak intensity, and obtaining compound (3) 6-bromo-1H-pyrazolo [3, 4-b) by combining with figure 2]The spectrum of the pyridine is shown in the specification,1H NMR(400MHz,DMSO)δ13.87(s,1H),8.22(d,J=8.4Hz,2H),7.39(d,J= 8.3Hz,1H)。
example 2
To n-butanol, 2, 6-dichloro-3-pyridinecarboxaldehyde (1056g,6.0mol,1eq.) and hydrazine hydrate (1414g,24.0mol,4eq, 85%) were added. Then, the mixture was stirred at room temperature for 0.5 h. After that, the temperature was raised to reflux overnight. Cooled and filtered, and a filter cake was collected, which was the compound (2) 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine (698g, 4.7mol), yield 78%, and the product was a white solid in color.
At room temperature, the compound (2), 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine (about 698g, 4.7mol, 1eq.) is dissolved in chloroform, liquid bromine (1502g, 9.4mol, 2.0eq.) is added dropwise, the temperature is kept at 40 ℃, after the liquid bromine is added dropwise, the mixture is heated and refluxed for 3 hours, cooled to room temperature, and then saturated sodium bicarbonate solution is slowly added dropwise under the ice bath condition to perform extraction reaction, and dichloromethane is added for liquid separation and extraction. The organic layer was collected, dried and concentrated to give a yellow powdery solid, giving compound (3), 6-bromo-1H-pyrazolo [3,4-b ] pyridine (698g, 3.5mol) in 75% yield.
Example 3
To n-butanol, 2, 6-dichloro-3-pyridinecarboxaldehyde (1056g,6.0mol,1eq.) and hydrazine hydrate (2120g,36.0mol,6eq, 85%) were added. Then, the mixture was stirred at room temperature for 1.0 h. After that, the temperature was raised to reflux overnight. Cooled and filtered, and a filter cake is collected, namely the compound (2) 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine (716g, 4.8mol), the yield is 80 percent, and the product is white solid in color.
At room temperature, the compound (2), 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine (about 716g, 4.8mol, 1eq.) is dissolved in chloroform, then liquid bromine (1534g, 9.6mol, 2.0eq.) is added dropwise, the temperature is kept at 40 ℃, after the liquid bromine is added dropwise, the mixture is heated and refluxed for 3 hours, cooled to room temperature, and then saturated sodium bicarbonate solution is slowly added dropwise under the ice bath condition to perform extraction reaction, and then dichloromethane is added for liquid separation and extraction. The organic layer was collected, dried and concentrated to give a yellow powdery solid, which was 75% yield of compound (3), 6-bromo-1H-pyrazolo [3,4-b ] pyridine (713g, 3.6 mol).
Comparative example 1
To tert-butanol, 2, 6-dichloro-3-pyridinecarboxaldehyde (176g,1.0mol,1eq.) and hydrazine hydrate (178g,3.0mol,3eq., 85%) were added. The temperature was raised to reflux overnight. The mixture was cooled and filtered, and a filter cake was collected, i.e., compound (2) 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine (41.8g, 0.28mol), and the yield of compound (2) 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine was calculated to be 28%.
At room temperature, the compound (2), 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine (41.8g, 0.28mol, 1eq.) is dissolved in chloroform, liquid bromine (90.4g, 0.56mol, 2eq.) is added dropwise, the temperature is kept at 40 ℃, after the liquid bromine is added dropwise, the mixture is heated and refluxed for 3 hours, cooled to room temperature, and then saturated sodium bicarbonate solution is slowly added dropwise under the ice bath condition to perform extraction reaction, and dichloromethane is added for liquid separation and extraction. The organic layer was collected, dried and concentrated to give compound (3) 6-bromo-1H-pyrazolo [3,4-b ] pyridine (41.6g, 0.21mol) in 75% yield as a yellow powdery solid.
Comparative example 2
To an organic solvent (n-butanol: t-butanol: DMF 80:10:10), 2, 6-dichloro-3-pyridinecarboxaldehyde (176g,1.0mol,1eq.) and hydrazine hydrate (412g,7.0mol,7eq, 85%) were added, and the mixture was heated to reflux overnight. The mixture was cooled and filtered, and a filter cake was collected, i.e., compound (2) 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine (67.1g, 0.45mol), and the yield of compound (2) 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine was calculated to be 45%.
At room temperature, the compound (2), 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine (67.1g, 0.45mol, 1eq.) is dissolved in chloroform, liquid bromine (143.8g, 0.90mol, 2.0eq.) is added dropwise, the temperature is kept at 40 ℃, the liquid bromine is added dropwise, heating and refluxing are carried out for 3H, after cooling to room temperature, saturated sodium bicarbonate solution is slowly added dropwise under the ice bath condition, and after the extraction reaction, dichloromethane is added, and liquid separation and extraction are carried out. The organic layer was collected, dried and concentrated to give 6-bromo-1H-pyrazolo [3,4-b ] pyridine compound (3) (66.8g, 0.34mol) as a yellow powdery solid in 75% yield.
Comparative example 3
To an organic solvent (n-butanol: t-butanol: DMF 70:25:5) were added 6-chloro-1H-pyrazolo [3,4-b ] pyridine (153.6g,1.0mol,1eq.) and hydrazine hydrate (294.5g,5.0mol,5eq, 85%), and the mixture was heated to reflux overnight. The mixture was cooled and filtered, and a filter cake was collected, i.e., compound (2) 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine (47.8g, 0.32mol), and the yield of compound (2) 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine was calculated to be 32%.
At room temperature, the compound (2), 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine (47.8g, 0.32mol, 1eq.) is dissolved in chloroform, liquid bromine (102.3g, 0.64mol, 2.0eq.) is added dropwise, the temperature is kept at 40 ℃, the liquid bromine is added dropwise, heating and refluxing are carried out for 3H, after cooling to room temperature, saturated sodium bicarbonate solution is slowly added dropwise under the ice bath condition, and after the extraction reaction, dichloromethane is added, and liquid separation and extraction are carried out. And collecting an organic layer, drying and concentrating to obtain a yellow powdery solid, wherein the compound (3) 6-bromo-1H-pyrazolo [3,4-b ] pyridine (47.5g, 0.24mol) is obtained, the yield is 75%, a byproduct is collected and stored, impurity positioning in subsequent chromatographic detection is facilitated, and waste liquid is recycled.
Although the present invention has been described with reference to the preferred embodiments, it is not intended to be limited thereto. Those skilled in the art can make various changes and modifications without departing from the spirit and scope of the invention. Therefore, the protection scope of the present invention should be determined by the appended claims.
Claims (1)
1. A synthetic method of a downstream product 6-bromo-1H-pyrazolo [3,4-b ] pyridine of 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine is characterized in that the synthetic route of the 6-bromo-1H-pyrazolo [3,4-b ] pyridine is as follows:
the specific synthesis steps are as follows:
step 1) under the condition of room temperature, stirring a compound (1), namely 2, 6-dichloro-3-pyridinecarboxaldehyde, and hydrazine hydrate in an organic solvent for reaction for 0.5-1H, heating to reflux overnight, cooling and filtering to obtain a compound (2), namely 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine; the compound (1) has the mol ratio of 2, 6-dichloro-3-pyridinecarboxaldehyde to hydrazine hydrate of 1 (4-6); the organic solvent is n-butyl alcohol, and the dosage of the n-butyl alcohol at least enables the compound (1), namely the 2, 6-dichloro-3-pyridinecarbaldehyde to be completely dissolved;
step 2) at room temperature, dissolving the compound (2) 6-hydrazino-1H-pyrazolo [3,4-B ] pyridine obtained in the step 1) in chloroform, then dropwise adding liquid bromine, keeping the temperature at 40 ℃, heating and refluxing for 1-6H after the liquid bromine is completely dropwise added, cooling to room temperature, and slowly dropwise adding saturated sodium bicarbonate solution in an ice bath to perform extraction and quenching reaction; dichloromethane is added for liquid separation and extraction, an organic layer is collected, dried and concentrated to obtain a yellow powdery solid compound (3), namely 6-bromo-1H-pyrazolo [3,4-B ] pyridine.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201810827151.2A CN108794470B (en) | 2018-07-25 | 2018-07-25 | 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine and synthesis method of downstream product thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201810827151.2A CN108794470B (en) | 2018-07-25 | 2018-07-25 | 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine and synthesis method of downstream product thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
CN108794470A CN108794470A (en) | 2018-11-13 |
CN108794470B true CN108794470B (en) | 2020-06-26 |
Family
ID=64078163
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201810827151.2A Active CN108794470B (en) | 2018-07-25 | 2018-07-25 | 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine and synthesis method of downstream product thereof |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN108794470B (en) |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1906965B1 (en) * | 2005-06-22 | 2015-05-06 | ChemoCentryx, Inc. | Azaindazole compounds and methods of use |
MA40957A (en) * | 2014-10-09 | 2017-09-19 | Biomarin Pharm Inc | HEPARANE SULPHATE BIOSYNTHESIS INHIBITORS TO TREAT DISEASES |
-
2018
- 2018-07-25 CN CN201810827151.2A patent/CN108794470B/en active Active
Also Published As
Publication number | Publication date |
---|---|
CN108794470A (en) | 2018-11-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN106608876B (en) | A kind of preparation method of high-purity Pa Boxini | |
CN108129288B (en) | Synthesis method of trans-3-hydroxycyclobutylformic acid | |
CN111675662A (en) | Preparation method of 2-trifluoromethyl substituted quinazolinone compound | |
CN110790763A (en) | Process for preparing pyridobipyrimidine and pyridobipyrazole derivatives | |
CN108623567A (en) | Ao Si replaces the preparation method of Buddhist nun | |
WO2022161469A1 (en) | Intermediate for thiohydantoin drug, and preparation method therefor and use thereof | |
CN110183445B (en) | Synthetic method of moxifloxacin and derivatives thereof | |
CN107540678B (en) | Method for preparing coumarin heteroaromatic ring compound and derivative thereof through intramolecular cross dehydrogenation coupling | |
CN113637002B (en) | Preparation method of Nilaparib | |
CN105949118A (en) | Preparation method of 2-aryl quinoline derivatives | |
CN107118215B (en) | A kind of preparation method for treating breast cancer medicines Rui Boxini intermediate | |
CN108794470B (en) | 6-hydrazino-1H-pyrazolo [3,4-b ] pyridine and synthesis method of downstream product thereof | |
CN101247806A (en) | SnAr process for preparing benzimidazole compounds | |
CN103980188A (en) | Synthetic method of perampanel, intermediate of perampanel and synthetic method of intermediate | |
Huang et al. | Preparation of a resin-bound cyclic malonic ester and a facile solid-phase synthesis of 4 (1H) quinolones | |
CN110016023B (en) | Simple preparation method of palbociclib | |
CN114014805B (en) | Preparation method of trifluoromethyl 2, 4-quinoline diketone compound | |
CN103665084A (en) | Method for preparing abiraterone acetate | |
JP7205059B2 (en) | Method for producing evodiamine | |
CN113912609B (en) | Preparation method of natural alkaloid tryptanthrin and derivatives thereof | |
CN109761914B (en) | Method for preparing 5-trifluoromethyl uracil | |
CN110172076B (en) | Quinoline derivative containing exocyclic double bond and preparation method thereof | |
CN110092751B (en) | Synthesis method of 2-alkyl quinoline | |
CN107954872B (en) | Method for synthesizing malonate type compound | |
CN108358866B (en) | Preparation method of febuxostat intermediate and application of febuxostat intermediate in preparation of febuxostat |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant | ||
CP01 | Change in the name or title of a patent holder | ||
CP01 | Change in the name or title of a patent holder |
Address after: Room 3501, 1077 Zuchongzhi Road, Pudong New Area, Shanghai, 200120 Patentee after: Shanghai bide Medical Technology Co.,Ltd. Address before: Room 3501, 1077 Zuchongzhi Road, Pudong New Area, Shanghai, 200120 Patentee before: BIDE PHARMATECH Ltd. |