CN111777604B - Synthesis method of 2-aminothiazole pyrimidine serving as CDK2 inhibitor - Google Patents
Synthesis method of 2-aminothiazole pyrimidine serving as CDK2 inhibitor Download PDFInfo
- Publication number
- CN111777604B CN111777604B CN202010690254.6A CN202010690254A CN111777604B CN 111777604 B CN111777604 B CN 111777604B CN 202010690254 A CN202010690254 A CN 202010690254A CN 111777604 B CN111777604 B CN 111777604B
- Authority
- CN
- China
- Prior art keywords
- reaction
- aminothiazole
- pyrimidine
- thiazole
- synthesizing
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention relates to the technical field of organic synthesis and medicines, and particularly discloses a method for synthesizing 2-aminothiazole pyrimidine serving as a CDK/2 inhibitor. The synthesis steps are as follows: conversion of the amino group to an isothiocyanate, reaction with a primary amine to form thiourea, Hantzsch thiazole synthesis, fluorination, and condensation of an enaminone with guanidine hydrochloride to form a pyrimidine ring. The method has the advantages that through 5 steps of reaction, the total yield reaches 35-48%. The invention has the advantages that: in the fluorination part, photocatalysis is adopted to replace the traditional fluorination method, the yield of the whole process is greatly increased, the reaction in the fluorination step enables the yield to be improved from 35% to 85%, and compared with the traditional fluorination method in a low-temperature ice salt bath, the method has mild conditions, only needs to be carried out at room temperature, and is a better process for synthesizing the CDK/2 inhibitor 2-aminothiazole pyrimidine.
Description
Technical Field
The invention relates to the technical field of organic synthesis and medicines, and particularly discloses a method for synthesizing 2-aminothiazole pyrimidine serving as a CDK/2 inhibitor.
Background
Cancer cells have an unlimited proliferation, disrupting the circulatory regulation of the cell, leading to a disturbance in the orderly division of the cell. Inhibitors of cyclin-dependent kinases (CDKs) which allow the cell cycle to be continuously operated, play a crucial role in cell cycle control, and are also one of the most promising fields of cancer therapy. Researchers at home and abroad have reported various types of Adenosine Triphosphate (ATP) -competitive CDK inhibitors, and some have been used in clinical diagnostics (Fischer, p.m.; Gianella-Borradori, a.exp.opin.invest.drugs 2003,12, 955.).
2-aminothiazolopyrimidines have been shown to be moderately potent CDK inhibitors (Wang, S.; Meads, C.; Wood, G et. al, J med. chem.,2004,47, 1662; Tadesse, S.; Yu, M.; Mekonen, L.B. et. al, J Med. chem.2017,60,1892.). The introduction of halogen atoms into drugs can affect the charge distribution of drug molecules, thereby enhancing the electrical binding with receptors. Because the electron-withdrawing effect of fluorine atoms is stronger, fluorine-containing medicaments account for a certain proportion of clinical medicaments. However, the traditional fluorination reaction needs fluorine reagent at low temperature and is kept at-5 ℃ for 3 hours, and the yield is only about 35%. The post-treatment is also complicated and requires a column-passing method to obtain a pure compound. Therefore, it is of great significance to develop a simple and efficient fluorination reaction.
Disclosure of Invention
The technical problem to be solved by the invention is to provide a simple photocatalytic preparation method of 2-aminothiazole pyrimidine serving as a CDK/2 inhibitor, and provide a synthetic method which is simple to operate and high in efficiency so as to meet the production requirement.
A method for synthesizing 2-aminothiazole pyrimidine serving as CDK/2 inhibitor comprises the following process flow:
the method comprises the following specific steps:
(1) synthesis of isothiocyanate: adding an organic solvent, aniline or aminocyclopentane, carbon disulfide, 4-dimethylaminopyridine and an organic base into a flask, stirring for 30 minutes at room temperature, and cooling to-5 ℃. Di-tert-butyl dicarbonate (Boc) is added at this temperature2O). Stirring at-5 deg.C for 10 min, heating to room temperature, stirring for 30 min, detecting by TLC plate, drying the reaction solution by spin-drying, filtering off insoluble substance with diethyl ether, drying the filtrate by spin-drying, and recrystallizing with petroleum ether to obtain isothiocyanate.
Wherein, the organic solvent can be ethanol, tetrahydrofuran, acetone or dichloromethane, and the organic base is triethylamine; the molar ratio of aniline or aminocyclopentane, carbon disulfide and di-tert-butyl dicarbonate is 1:1: 0.9; the amount of triethylamine added was 10% mmol equivalent and the amount of 4-dimethylaminopyridine was 1% mmol equivalent.
(2) And (3) synthesizing thiourea: adding isothiocyanate and ammonia water into the reaction tube, stirring in an organic solvent at room temperature for 18-24 hours, and recrystallizing the precipitated solid with ethyl acetate to obtain the pure thiourea derivative.
Wherein the organic solvent is methanol or ethanol, and the ammonia water is excessive.
(3) Hantzsch thiazole synthesis: under the ice-water bath, a neutral anhydrous solvent, pyridine and thiourea derivatives are added into a flask, and 3-chloro-2, 4-pentanedione is slowly added dropwise. The temperature was then raised to room temperature, stirred for 4 hours and the reaction checked by TLC spot plate. The precipitated solid was recrystallized from ethyl acetate to obtain pure 2-aminothiazole.
Wherein the neutral anhydrous solvent can be acetonitrile or anhydrous methanol; the molar ratio of the thiourea derivative, the 3-chloro-2, 4-pentanedione and the pyridine is 1:1: 1.
(4) Synthesis of thiazole acrylamide: n, N-dimethylformamide-dimethylamine (DMF-DMA) and 2-aminothiazole were added to the flask. The reaction temperature was raised to 120 ℃ and the reaction was carried out for 6 hours. And detecting the reaction by TLC spot plates, concentrating the reaction solution after the reaction is finished, and recrystallizing ethyl acetate to obtain the thiazole acrylamide.
The molar ratio of the 2-aminothiazole to the N, N-dimethylformamide-dimethylamine is 1:2-1: 5.
(5) Fluorination reaction under the condition of illumination, thiazole acrylamide, a fluorine reagent, a photocatalyst and an organic solvent are added into a reaction tube, and the reaction is carried out for 1 hour at room temperature. And (3) detecting the reaction by TLC spot plates, concentrating the reaction solution after the reaction is finished, and recrystallizing petroleum ether to obtain the fluorinated thiazole acrylamide.
Wherein the fluorine reagent is [ 1-chloromethyl-4-fluorine-1, 4-diazotized bicyclo 2.2.2 octane bis (tetrafluoroborate) salt 3-methylamine-alizarin-diacetic acid, and the structural formula is shown in the specification
(CAS NO.140681-55-6)](ii) a The photocatalyst may be Ru (bpy)3(PF6)2Eosin Y or rhodamine B; the organic solvent may be acetonitrile, tetrahydrofuran, anhydrous ethanol or Dimethylacetamide (DMA).
The molar ratio of the thiazole acrylamide to the fluorine reagent is 1:1.2-1: 1.5.
The amount of photocatalyst added was 5% mmol equivalent.
(6) Formation of pyrimidine ring fluoride, guanidine hydrochloride and inorganic base were added to the reaction tube and refluxed in diethylene glycol monomethyl ether for 6 hours. The inorganic base may be sodium hydroxide or potassium hydroxide.
The molar ratio of the fluorinated thiazole acrylamide to the guanidine hydrochloride to the inorganic base is 1:1: 2.
The structural formula of the 2-aminothiazole pyrimidine or the pharmaceutically acceptable salt thereof prepared by the method is shown as the formula (I):
the invention has the advantages that: 2-aminothiazole pyrimidine is an important CDK/2 inhibitor and has wide application in medicine and pharmacology. The method of the invention uses fluorine reagent to carry out fluorine addition under the photocatalysis condition, can carry out reaction at room temperature, and shortens the time to 1 hour. The yield reaches 83-85%, and the fluoride can be obtained by simple recrystallization in the post-treatment. The new method is more mild and convenient, the yield is improved from the traditional 35 percent to 85 percent, and the yield is greatly improved.
Detailed Description
The reaction process and the structural formula of the obtained product are shown in the specification
Example 12- (Cyclopentylamine) -4-methylthiazole-2-fluoro-propenone 6a
The flask was charged with anhydrous ethanol (3mL), aminocyclopentane (44mmol), carbon disulfide (44mmol) and triethylamine (4.4mmol), stirred at room temperature for 30 minutes and cooled to-5 ℃. At this temperature, di-tert-butyl dicarbonate (Boc) is added in solution2O) (4.36mmol) in absolute ethanol (2mL), 4-dimethylaminopyridine (4.5% mmol). Stirring at-5 deg.C for 10 min, heating to room temperature, stirring for 30 min, detecting by TLC spot plate, drying the reaction solution, filtering off insoluble substance with diethyl ether, drying the filtrate, and recrystallizing with petroleum ether to obtain isothiocyanate with yield of 88%.
Isothiocyanate (50mmol) and ammonia (30mL) were added to the reaction tube, and stirred in methanol at room temperature for 20 hours, and the precipitated solid was recrystallized from ethyl acetate to give pure thiourea in 85% yield.
In an ice-water bath, anhydrous methanol (15mL), pyridine (1.5mL) and thiourea (48mmol) were added to the flask, and 3-chloro-2, 4-pentanedione (48mmol) was slowly added dropwise. The temperature was then raised to room temperature, stirred for 4 hours and the reaction checked by TLC spot plate. The precipitated solid was recrystallized from ethyl acetate to obtain pure 2-aminothiazole in a yield of 90%.
Into the flask were added N, N-dimethylformamide-dimethylamine (DMF-DMA, 38mmol) and 2-aminothiazole (21 mmol). The reaction temperature was raised to 120 ℃ and the reaction was carried out for 6 hours. And detecting the reaction by a TLC spot plate, concentrating the reaction solution after the reaction is finished, and recrystallizing by ethyl acetate to obtain the thiazole acrylamide with the yield of 79%.
Under the condition of illumination, compound thiazole acrylamide 5a (2.0mmol), fluorinating agent (3.0mmol), tris (2,2' -bipyridine) ruthenium bis (hexafluorophosphate) salt Ru (bpy)3(PF6)2(5% mmol) and dry acetonitrile (15mL) were added to a 50mL flask and the reaction was stirred at room temperature for 1 hour. TLC spot plate detection reaction, after finishing the reaction, concentrating the reaction solution, recrystallizing with petroleum ether, and filtering to obtain pure compound 6a with the yield of 85%.1H NMR(500MHz,CDCl3)δ6.88(d,J＝24.8Hz,1H),3.78-3.74(m,1H),3.08(s,6H),2.54(s,3H),2.02-2.08(m,2H),1.55-1.74(m,6H).
Example 22- (Aniline) -4-methylthiazole-2-fluoro-propenone 6b
Anhydrous ethanol (3mL), aniline (44mmol), carbon disulfide (44mmol) and triethylamine (4.4mmol) were added to the flask, stirred at room temperature for 30 minutes and then cooled to-5 ℃. At this temperature, di-tert-butyl dicarbonate (Boc) is added in solution2O) (4.36mmol) in absolute ethanol (2mL), 4-dimethylaminopyridine (4.5% mmol). Stirring at-5 deg.C for 10 min, heating to room temperature, stirring for 30 min, detecting by TLC spot plate, drying the reaction solution, filtering off insoluble substance with diethyl ether, drying the filtrate, and recrystallizing with petroleum ether to obtain isothiocyanate with yield of 75%.
Isothiocyanate (50mmol) and ammonia (30mL) were added to the reaction tube, and stirred in methanol at room temperature for 24 hours, and the precipitated solid was recrystallized from ethyl acetate to give pure thiourea in a yield of 90%.
In an ice-water bath, anhydrous methanol (15mL), pyridine (1.5mL) and thiourea (48mmol) were added to the flask, and 3-chloro-2, 4-pentanedione (48mmol) was slowly added dropwise. The temperature was then raised to room temperature, stirred for 4 hours and the reaction checked by TLC spot plate. The precipitated solid was recrystallized from ethyl acetate to obtain pure 2-aminothiazole in a yield of 85%.
The flask was charged with 2-aminothiazole 4(21mmol) and N, N-dimethylformamide-dimethylamine (DMF-DMA, 42 mmol). The reaction temperature was raised to 120 ℃ and the reaction was carried out for 6 hours. Detecting the reaction by TLC point plate, concentrating the reaction solution after the reaction is finished, and recrystallizing ethyl acetate to obtain thiazole acrylamide with the yield of 79 percent
Under the condition of illumination, compound thiazole acrylamide 5b (2.0mmol), fluorinating agent (3.0mmol), tris (2,2' -bipyridine) ruthenium bis (hexafluorophosphate) salt Ru (bpy)3(PF6)2(5% mmol) and dry acetonitrile (15mL) were added to a 50mL flask and the reaction was stirred at room temperature for 1 hour. The reaction was checked by TLC plate chromatography, after completion the reaction was concentrated, recrystallized from petroleum ether and filtered to give pure compound 6b in 83% yield.1H NMR(500MHz,CDCl3)δ10.40(br,1H),7.23-7.18(m,2H),6.83-6.81(m,1H),6.45(d,J＝8.4Hz,2H),6.18-6.15(m,1H),3.78-3.74(m,1H),3.06(s,6H),2.22-2.18(m,1H),1.55-1.74(m,3H).
Example 3
Under the illumination condition, the compound thiazole acrylamide 5b (2.0mmol), a fluorine reagent (2.4mmol), tris (2,2' -bipyridine) ruthenium bis (hexafluorophosphate) salt Ru (bpy)3(PF6)2(5% mmol) and dry acetonitrile (15mL) were added to a 50mL flask and the reaction was stirred at room temperature for 1 hour. TLC spot plate detection reaction, after finishing reaction, concentrating the reaction solution, recrystallizing with petroleum ether, and filtering to obtain pure compound 6b with the yield reaching 70%.
Example 4
Thiazole acrylamide (2.0mmol), a fluorine reagent (3.0mmol), pyrrhone Y (5% mmol) and anhydrous acetonitrile (15mL) were added to a 50mL flask under light conditions, and the reaction was stirred at room temperature for 1 hour. The reaction was checked by TLC plate chromatography, after completion the reaction was concentrated, recrystallized from petroleum ether and filtered to give pure compound 6a in 52% yield.
Example 5
Under the illumination condition, compound 5a (2.0mmol), fluorine reagent (3.0mmol), tris (2,2' -bipyridine) ruthenium bis (hexafluorophosphate) salt Ru (bpy)3(PF6)2(5% mmol) and dry methanol (15mL) were added to a 50mL flask and the reaction was stirred at room temperature for 1 hour. TLC spot plate detection reactionAfter the reaction is finished, the reaction solution is concentrated, recrystallized by petroleum ether and filtered to obtain pure compound 6a, and the yield reaches 72%.
Example 6
Under the illumination condition, compound 5a (2.0mmol), fluorine reagent (3.0mmol), tris (2,2' -bipyridine) ruthenium bis (hexafluorophosphate) salt Ru (bpy)3(PF6)2(5% mmol) and tetrahydrofuran (15mL) were added to a 50mL flask and the reaction was stirred at room temperature for 1 hour. The reaction was checked by TLC plate chromatography, after completion the reaction was concentrated, recrystallized from petroleum ether and filtered to give pure compound 6a in 52% yield.
Example 7N-Cyclopentan-2-amino 5-Fluorothiazolopyrimidine 7a
Adding the compound 6a (2.0mmol), NaOH (4.0mmol), guanidine hydrochloride (4.0mmol) and diethylene glycol monomethyl ether (15mL) into a 50mL flask, raising the reaction temperature to 130 ℃ for reflux reaction for 6 hours, detecting the reaction by a TLC point plate, drying the filtrate by spinning, and further separating and purifying the crude product by silica gel column chromatography to obtain 7a.1H NMR(500MHz,CDCl3)δ8.07(d,J＝3.5Hz,1H,),5.75(d,J＝5.8Hz,1H,),5.06(s,2H),3.83-3.79(m,1H),2.52(d,J＝2.5Hz,3H),2.12-2.05(m,2H),1.76-1.58(m,6H).
Example 8N-phenyl-2-amino-5-fluorothiazolopyrimidine 7b
7b synthetic procedure reference is made to 7a.1H NMR(500MHz,CDCl3)δ10.36(br,1H),8.62(d,J＝7.8Hz,1H),7.25-7.21(m,2H),6.85-6.83(m,1H),6.54(s,1H),6.45(d,J＝8.2Hz,2H),3.82-3.76(m,1H),2.56-2.53(m,1H),1.09-1.06(m,3H).
Comparative example 1
Compound 5a (2.0mmol), fluoro reagent (3.0mmol), tris (2,2' -bipyridine) ruthenium bis (hexafluorophosphate) salt Ru (bpy) were placed in a tin foil-coated flask in the dark3(PF6)2(5% mmol) and dry acetonitrile (15mL) were added to a 50mL flask and the reaction was stirred at room temperature for 1 hour. The reaction was detected by TLC plate and found to be non-reactive.
The present invention is not limited to the above-described embodiments, and any obvious improvements, substitutions or modifications can be made by those skilled in the art without departing from the spirit of the present invention.
Claims (7)
1. A synthetic method of 2-aminothiazole pyrimidine is characterized by comprising the following steps:
(1) conversion of amino group to isothiocyanate by adding organic solvent, aniline or aminocyclopentane, carbon disulfide, 4-dimethylaminopyridine and organic base to flask, stirring at 0-23 deg.C for 30 min, cooling to-5 deg.C, adding di-tert-butyl dicarbonate (Boc)2O), continuously stirring at-5 ℃ for 10 minutes, raising the reaction temperature to room temperature, stirring for 30 minutes, detecting the reaction by TLC spot plate, spin-drying the reaction liquid after the reaction is finished, filtering out insoluble substances by using diethyl ether, spin-drying the filtrate, and recrystallizing by using petroleum ether to obtain isothiocyanate; the structural formula is R1NCS，R1Ph or c-Pent;
(2) generation of thiourea:
adding isothiocyanate and ammonia water into the reaction tube, stirring in organic solvent at room temperature for 18-24 hr, and recrystallizing the precipitated solid with ethyl acetate to obtain pure thiourea derivative
(3) Hantzsch thiazole synthesis: under the condition of ice-water bath, adding an anhydrous solvent, pyridine and a thiourea derivative into a flask, slowly dropwise adding 3-chloro-2, 4-pentanedione, then heating to room temperature, stirring for 4 hours, detecting the reaction by a TLC (thin layer chromatography) spot plate, and recrystallizing the precipitated solid with ethyl acetate to obtain pure 2-aminothiazole; the structural formula is as follows:
；
(4) synthesis of thiazole acrylamide: adding into a reaction tubeN,NDimethyl formamide-dimethylamine (DMF-DMA) and 2-aminothiazole, raising the reaction temperature to 120 ℃, reacting for 6 hours, detecting the reaction by TLC spot plate, concentrating the reaction solution after the reaction, and recrystallizing ethyl acetateObtaining thiazole acrylamide; the structural formula is as follows:
；
(5) fluorination reaction: under the condition of illumination, adding thiazole acrylamide, a fluorine reagent, a photocatalyst and an organic solvent into a reaction tube, and reacting for 1 hour at room temperature; after the reaction, recrystallizing by using diethyl ether to obtain fluoride; the structural formula is as follows:
；
the fluorine reagent is [ 1-chloromethyl-4-fluorine-1, 4-diazotized bicyclo 2.2.2 octane bis (tetrafluoroborate) 3-methylamine-alizarin-diacetic acid, and the structural formula is
；
The photocatalyst is Ru (bpy)3(PF6)2Eosin Y or rhodamine B;
the molar ratio of the thiazole acrylamide to the fluorine reagent is 1:1.2-1: 1.5;
the addition amount of the photocatalyst is 5% mmol equivalent;
(6) formation of the pyrimidine ring: adding fluoride, guanidine hydrochloride and inorganic base into a reaction tube, and refluxing in dioxy ethanol for 6 hours;
the structural formula of the 2-aminothiazole pyrimidine is shown as the formula (I)
Formula (I).
2. The method for synthesizing 2-aminothiazole pyrimidine according to claim 1, characterized in that the organic solvent in step (1) is: ethanol, tetrahydrofuran, acetone or dichloromethane; the organic base is triethylamine; the molar ratio of aniline or aminocyclopentane, carbon disulfide and di-tert-butyl dicarbonate is 1:1: 0.9; the addition amount of triethylamine is 10% mmol of aniline or aminocyclopentane, and the use amount of 4-dimethylaminopyridine is 1% mmol equivalent.
3. The method for synthesizing 2-aminothiazole pyrimidine according to claim 1, characterized in that the organic solvent in step (2) is methanol or ethanol, and ammonia water is in excess.
4. The method for synthesizing 2-aminothiazole pyrimidine according to claim 1, characterized in that the molar ratio of the thiourea derivative, 3-chloro-2, 4-pentanedione and pyridine in the step (3) is 1:1:1, and the anhydrous solvent is acetonitrile or anhydrous methanol.
5. The method of claim 1, wherein the 2-aminothiazole pyrimidine of step (4) is synthesized with an aminothiazoleN,NThe molar ratio of the dimethylformamide to the dimethylamine is from 1:2 to 1: 5.
6. The method for synthesizing 2-aminothiazole pyrimidine according to claim 1, characterized in that the organic solvent of step (5) is anhydrous acetonitrile, tetrahydrofuran, anhydrous methanol or Dimethylacetamide (DMA).
7. The method for synthesizing 2-aminothiazole pyrimidine according to claim 1, characterized in that the inorganic base in the step (6) is sodium hydroxide or potassium hydroxide; the molar ratio of the fluorinated thiazole acrylamide to the guanidine hydrochloride to the inorganic base is 1:1: 2.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010690254.6A CN111777604B (en) | 2020-07-17 | 2020-07-17 | Synthesis method of 2-aminothiazole pyrimidine serving as CDK2 inhibitor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010690254.6A CN111777604B (en) | 2020-07-17 | 2020-07-17 | Synthesis method of 2-aminothiazole pyrimidine serving as CDK2 inhibitor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111777604A CN111777604A (en) | 2020-10-16 |
| CN111777604B true CN111777604B (en) | 2021-12-21 |
Family
ID=72764481
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010690254.6A Active CN111777604B (en) | 2020-07-17 | 2020-07-17 | Synthesis method of 2-aminothiazole pyrimidine serving as CDK2 inhibitor |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111777604B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113912548A (en) * | 2021-11-19 | 2022-01-11 | 浙江师范大学行知学院 | Abelide and preparation method of intermediate thereof |
| CN114478529A (en) * | 2022-03-01 | 2022-05-13 | 无锡捷化医药科技有限公司 | CDK inhibitor and preparation method thereof |
| CN115368282A (en) * | 2022-08-09 | 2022-11-22 | 吉安宏达秋科技有限公司 | Method for synthesizing 1, 3-disubstituted thiourea in aqueous phase |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0515743D0 (en) * | 2005-07-30 | 2005-09-07 | Astrazeneca Ab | Chemical compounds |
| CN108349964B (en) * | 2015-08-04 | 2021-06-01 | 常州千红生化制药股份有限公司 | N- (pyridin-2-yl) -4- (thiazol-5-yl) pyrimidin-2-amines as therapeutic compounds |
-
2020
- 2020-07-17 CN CN202010690254.6A patent/CN111777604B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN111777604A (en) | 2020-10-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111777604B (en) | Synthesis method of 2-aminothiazole pyrimidine serving as CDK2 inhibitor | |
| JP6921087B2 (en) | Ruxolitinib synthesis process | |
| CA3158166A1 (en) | Process for the preparation of 2-cyanoethyl (4s)-4-(4-cyano-2-methoxy-phenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylate by resolution of racemates by means of diastereomeric tartaric acid esters | |
| EP3658552B1 (en) | Process for preparing n-(5-((4-(4-((dimethylamino)methyl)-3-phenyl-1h-pyrazol-1-yl)pyrimidin-2-yl)amino)-4-methoxy-2-morpholinophenyl)acrylamide by reacting the corresponding amine with a 3-halo-propionyl chloride | |
| CN111704646B (en) | Steroid compound and preparation method and application thereof | |
| EA038078B1 (en) | Intermediates useful for the synthesis of a selective inhibitor against protein kinase and processes for preparing the same | |
| CN110790689B (en) | Synthetic method of 1, 1-difluoro-2-isonitrile-ethyl phenyl sulfone compound | |
| JPS6018653B2 (en) | Process for producing novel 2,6-disubstituted 2-phenylimino-imidazolidine and its acid addition salt | |
| CN102267983B (en) | Sym-triazine derivative compounds containing sym-tetrazine rings and preparation method thereof | |
| EP3658553B1 (en) | Intermediates useful for the synthesis of aminopyrimidine derivatives, process for preparing the same, and process for preparing aminopyrimidine derivatives using the same | |
| CN117105845A (en) | Electrophilic trifluoro methyl selenizing reagent and preparation method and application thereof | |
| EP1215206B1 (en) | Processes for the preparation of 4(5)-amino-5(4)-carboxamidoimidazoles and intermediates thereof | |
| KR20140042805A (en) | Intermediate for synthesizing caspofungin and preparation method therefor | |
| CN102127076A (en) | Method for synthesizing 2,3-dihydropyrido[2,3-d]pyrimidine-4-(3H)-one | |
| CN105272921A (en) | Method for preparing Ceritinib and intermediate compound of Ceritinib | |
| CN109265409B (en) | Synthesis method of 2-substituted benzoxazole, 2-substituted benzothiazole and derivatives thereof | |
| JPH0641135A (en) | Imidazopteridine derivative and its production | |
| KR100497105B1 (en) | 3,4-Dihydroquinazoline Derivatives and Process for the Preparation Thereof | |
| CN110857299B (en) | Synthesis method of 3-thiocyanoimidazo [1,5-a ] quinoline compound | |
| Kitamura et al. | Synthesis, structure, and reaction of chiral 2-azidoimidazolinium salts:(7aS)-3-azido-5, 6, 7, 7a-tetrahydro-2-[(1R)-1-phenylethyl]-1H-pyrrolo [1, 2-c] imidazolium hexafluorophosphate and 2-azido-1, 3-bis [(S)-1-phenylethyl] imidazolinium hexafluorophosphate | |
| CN110862385A (en) | Application of copper catalyst in preparation of thiazoloquinazolinone derivative through reaction of 1-thiazolylindole compound and tert-butyl nitrite | |
| CN109988172B (en) | Synthesis method of pyrazolo [1,5-A ] pyrimidine heterocyclic compound and derivative | |
| EP4375282A1 (en) | Preparation method for hepatitis b virus nucleocapsid inhibitor | |
| Zhou et al. | Synthesis and analysis of 1-methyl-4-phenyl-1H-imidazol-2-amine | |
| CN116283707A (en) | Synthesis method of indole compound promoted by visible light |
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 |