CN102060862A - Synthesis method of 5,7-dichlorothiazole[4,5-d]pyrimidine - Google Patents
Synthesis method of 5,7-dichlorothiazole[4,5-d]pyrimidine Download PDFInfo
- Publication number
- CN102060862A CN102060862A CN2009102018009A CN200910201800A CN102060862A CN 102060862 A CN102060862 A CN 102060862A CN 2009102018009 A CN2009102018009 A CN 2009102018009A CN 200910201800 A CN200910201800 A CN 200910201800A CN 102060862 A CN102060862 A CN 102060862A
- Authority
- CN
- China
- Prior art keywords
- thiazole
- reaction
- pyrimidine
- ethyl formate
- amino
- 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.)
- Pending
Links
Landscapes
- Thiazole And Isothizaole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a synthesis method of 5,7-dichlorothiazole[4,5-d]pyrimidine. The synthesis method mainly solves the technical problems of complex posttreatment, difficult separation and purification, low yield, high synthesis cost, low applicability and the like in the conventional synthesis method. The synthesis method comprises the following steps of: reacting cyanamide with carbon disulfide and alkali metal hydroxide to obtain a cyanoimide dithioformic alkali metal salt; reacting the cyanoimide dithioformic alkali metal salt with a methylation reagent to selectively generate the corresponding monopotassium 2; performing a ring-closing reaction on the monopotassium 2 and bromoacetate under an alkaline condition to generate 2-methylmercapto-4-amino-5-ethyl formate thiazole 3; reducing the methylmercapto in the 2-methylmercapto-4-amino-5-ethyl formate thiazole 3 under an acidic condition by using a reducing reagent to obtain 4-amino-5-ethyl formate thiazole 4; converting the amino in the 4-amino-5-ethyl formate thiazole 4 into isocyanate and then reacting with an ammonia reagent to generate the corresponding 4-urea-5-ethyl formate thiazole 5; performing a ring-closing reaction on the 4-urea-5-ethyl formate thiazole 5 under an alkaline condition to obtain [4,5-d]thiazole5,7-dihydroxy pyrimidine 6; and reacting the [4,5-d]thiazole5,7-dihydroxy pyrimidine 6 with a chlorinated reagent to obtain the 5,7-dichlorothiazole[4,5-d]pyrimidine 7. The 5,7-dichlorothiazole[4,5-d]pyrimidine can be prepared quickly and conveniently through the synthesis route.
Description
Technical field:
The present invention relates to a kind of important medicine intermediate 5, the synthetic method of 7-dichloro thiazole [4,5-d] pyrimidine.
Background technology:
5,7-dichloro thiazole [4,5-d] pyrimidine is a kind of important medicine intermediate, and it can be used for synthesizing a lot of small-molecule drugs.With it is that template can synthesize a lot of drug molecules, and these drug molecules have good bio-pharmacology activity, especially have antitumour activity.This quasi-molecule is by suppressing the activity that the PI3 kinases comes control cancer cell, so this class drug molecule has broad application prospects.By retrieval, WO2009042607, US5606091A, WO2005049613 has reported 5,7-dichloro thiazole [4,5-d] pyrimidine synthetic route, but these synthetic route reaction conditionss are violent, yield is lower, are difficult to carry out scale operation.
Summary of the invention:
The object of the present invention is to provide a kind of 5, the new synthetic method of 7-dichloro thiazole [4,5-d] pyrimidine, mainly solve aftertreatment complexity, separation and purification difficulty that existing synthetic method lacks and exists, technical problems such as productive rate is low, synthesizes the cost height, and suitability is wideless.
Technical scheme of the present invention: 5, the synthetic method of 7-dichloro thiazole [4,5-d] pyrimidine may further comprise the steps:
The first step reaction is a raw material with cyanamide 1, obtains cyano group imide dithio formic acid an alkali metal salt with dithiocarbonic anhydride and alkali metal hydroxide reaction; Can optionally generate corresponding monopotassium salt 2 with the methylating reagent reaction;
The reaction of second step, monopotassium salt are closed ring with ethyl bromoacetate and are generated 2-methylthio group-4-amino-5-ethyl formate thiazole 3 under alkaline condition;
Methylthio group in three-step reaction 2-methylthio group-4-amino-5-ethyl formate thiazole 3 obtains 4-amino-5-ethyl formate thiazole 4 with going back the original reagent reduction under acidic conditions;
Amido in four-step reaction 4-amino-5-ethyl formate thiazole 4 changes into isocyanic ester earlier, generates corresponding 4-urea-5-ethyl formate thiazole 5 with ammonia reagent again;
The 5th step reaction 4-urea-5-ethyl formate thiazole 5 advances-goes on foot to close ring and obtains [4,5-d] thiazole 5,7-dihydroxy-pyrimidine 6 under alkaline condition;
Six-step process [4,5-d] thiazole 5,7-dihydroxy-pyrimidine 6 obtains the finished product 5,7-dichloro thiazole [4,5-d] pyrimidine 7 with the chlorinating agent reaction.
Chemical equation is as follows:
The first step is reflected in the organic solvent carries out, and organic solvent is a kind of in methyl alcohol, ethanol, the ethyl acetate; Alkali metal hydroxide is with sodium hydroxide or potassium hydroxide; Methylating reagent is with methyl iodide or methyl-sulfate; The concentration expressed in percentage by weight 10～80% of alkali; Temperature of reaction is 0～40 ℃; Reaction times is 10～20 hours.
Second step was reflected in the organic solvent and carries out, and organic solvent is a kind of in methyl alcohol, ethanol, ethyl acetate or the acetone; A kind of with in triethylamine, pyridine or the nitrogen methylmorpholine of alkali; Temperature of reaction is 0～100 ℃; Reaction times is 1～16 hour.
Acid in the three-step reaction is a kind of in hydrochloric acid, sulfuric acid or the phosphoric acid; The concentration expressed in percentage by weight 10～50% of acid; Also original reagent is a kind of in zinc powder and the iron powder.Temperature of reaction is 0～40 ℃; Reaction times is 1～16 hour.
The four-step reaction solvent is a kind of in methylene dichloride, tetrahydrofuran (THF) or the toluene; Generate a kind of with in phosgene, trichloromethylchloroformate, triphosgene or the carbonyl dimidazoles of isocyanate compound; Ammonia reagent is a kind of in ammoniacal liquor, liquefied ammonia or the ammonium chloride.Temperature of reaction is 0～40 ℃; Reaction times is 1～16 hour.
The 5th step reaction solvent is methyl alcohol or ethanol; Alkali is with sodium hydroxide or potassium hydroxide; The concentration expressed in percentage by weight 10～80% of alkali; Temperature of reaction is 0～100 ℃; Reaction times is 1～20 hour.
The six-step process chlorinating agent is a kind of in phosphorus oxychloride, sulfur oxychloride or the phosphorus pentachloride; Temperature of reaction is 0～120 ℃; Reaction times is 1～20 hour.
The invention has the beneficial effects as follows: the invention provides a kind of synthetic route of novelty, can prepare a kind of important medicine intermediate 5 quickly and easily, 7-dichloro thiazole [4,5-d] pyrimidine from raw material cyanamide cheap, that be easy to get.This process yield can reach 82%, and suitable scale operation.
Embodiment: following example helps to understand content of the present invention, the present invention includes but is not limited to following related content:
Synthesizing of cyano group imide dithio formic acid sylvite 2
Embodiment 1
(453g 5.95mmol) is dissolved in methyl alcohol (1.3L) to dithiocarbonic anhydride, and (500g 5.95mmol), is cooled to 0 ℃ with this solution to the cyanamide aqueous solution of adding 50% then.(666g, 11.9mmol) water-soluble (800mL) slowly adds this solution in the above-mentioned methanol solution to get potassium hydroxide.After dropwising, reaction solution is raised to room temperature, stirs 12 hours.Then reaction solution is cooled to zero degree, drips methyl iodide (844g, methanol solution 5.95mmol) (350mL).After dropwising, reaction solution stirring at room 12 hours.After reaction system is spin-dried for, add acetone (2.0L), stir and after 5 minutes solid insoluble is removed by filter, mother liquor is spin-dried for and obtains crude product.Add ethyl acetate (2.0L) in the crude product, stir after 5 minutes again insolubles to be filtered and remove, be spin-dried for mother liquor and obtain 900 and digest compound cyano group imide dithio formic acid sylvite 2.(yield: 80%)
Embodiment 2
(453g 5.95mmol) is dissolved in ethanol (1.3L) to dithiocarbonic anhydride, and (500g 5.95mmol), is cooled to 0 ℃ with this solution to the cyanamide aqueous solution of adding 50% then.(476g, 11.9mmol) water-soluble (800mL) slowly adds this solution in the above-mentioned methanol solution to get sodium hydroxide.After dropwising, reaction solution is raised to room temperature, stirs 10 hours.Then reaction solution is cooled to zero degree, drips methyl-sulfate (559g, ethanolic soln 5.95mmol) (350mL).After dropwising, reaction solution stirring at room 10 hours.After reaction system is spin-dried for, add acetone (2.0L), stir and after 5 minutes solid insoluble is removed by filter, mother liquor is spin-dried for and obtains crude product.Add ethyl acetate (2.0L) in the crude product, stir after 5 minutes again insolubles to be filtered and remove, be spin-dried for mother liquor and obtain 600 and digest compound cyano group imide dithio formic acid sylvite 2.(yield: 53%)
Embodiment 3
(453g 5.95mmol) is dissolved in ethyl acetate (1.3L) to dithiocarbonic anhydride, and (500g 5.95mmol), is cooled to 0 ℃ with this solution to the cyanamide aqueous solution of adding 50% then.(400g, 7.1mmol) water-soluble (800mL) slowly adds this solution in the above-mentioned methanol solution to get potassium hydroxide.After dropwising, reaction solution is raised to 40 degree, stirs 12 hours.Then reaction solution is cooled to zero degree, drips methyl iodide (844g, methanol solution 5.95mmol) (350mL).After dropwising, reaction solution 40 degree stirred 12 hours.After reaction system is spin-dried for, add acetone (2.0L), stir and after 5 minutes solid insoluble is removed by filter, mother liquor is spin-dried for and obtains crude product.Add ethyl acetate (2.0L) in the crude product, stir after 5 minutes again insolubles to be filtered and remove, be spin-dried for mother liquor and obtain 710 and digest compound cyano group imide dithio formic acid sylvite 2.(yield: 63%)
2.2-methylthio group-4-amino-5-ethyl formate thiazole 3 is synthetic
Embodiment 4
(1020g 5.99mmol) is dissolved in ethanol (6.0L), and (994g, 5.99mmol), white depositions appears in reaction system slowly to add bromoethyl acetate then with cyano group imide dithio formic acid sylvite 2.This white suspension is heated to 80～100 ℃, reacted 1 hour.Behind the cool to room temperature, (121g 1.20mol), finishes, again with 80～100 ℃ of reaction solution heating 3 hours carefully to add triethylamine.After the cooling solvent in the reaction system is spin-dried for, the solid mixture that obtains is added in the frozen water, stirred 5 minutes, after filtration, washing, drying obtain 1180 gram product 2-methylthio group-4-amino-5-ethyl formate thiazoles 3.(yield: 90%)
Proton nmr spectra (DMSO, 400MHz), δ ppm:6.98 (br, 2H), 4.14 (q, J=7.1Hz, 2H), 2.63 (s, 3H), 1.20 (t, J=7.2Hz, 3H).
Embodiment 5
(1020g 5.99mmol) is dissolved in methyl alcohol or ethyl acetate (6.0L), and (994g, 5.99mmol), white depositions appears in reaction system slowly to add bromoethyl acetate then with cyano group imide dithio formic acid sylvite 2.This white suspension is heated to 80 ℃, reacted 1 hour.After being cooled to zero degree, (121g 1.20mol), finishes, again with 100 ℃ of reaction solution heating 16 hours carefully to add pyridine or nitrogen methylmorpholine.After the cooling solvent in the reaction system is spin-dried for, the solid mixture that obtains is added in the frozen water, stirred 5 minutes, after filtration, washing, drying obtain 900 gram product 2-methylthio group-4-amino-5-ethyl formate thiazoles 3.(yield: 69%)
3.4-amino-5-ethyl formate thiazole 4 is synthetic
Embodiment 6
With 2-methylthio group-4-amino-5-ethyl formate thiazole 3 (10.0g, 45.9mmol) be dissolved in methyl alcohol (100mL) (can suitably heat with dissolving) fully, at room temperature, add zinc powder (8.80g, 137.7mmol), (30.6mL, 91.8mmol) (compound method: get the 7.7mL concentrated hydrochloric acid and be dissolved in 22.9mL methyl alcohol) have gas to produce in the reaction process slowly to drip the 3N hydrochloric acid soln again.Behind the room temperature reaction 2 hours, the thin-layer chromatography monitoring shows that raw material consumption finishes.Reaction solution is poured in the saturated sodium carbonate solution (500mL), add diatomite filtration, filtrate is used dichloromethane extraction (300mL * 2), merge organic phase and use the saturated common salt water washing again, anhydrous sodium sulfate drying, after removing by filter siccative, concentrated filtrate obtains 6.32 gram product 4-amino-5-ethyl formate thiazoles 4.(yield: 80%)
1Proton nmr spectra (DMSO, 400MHz), δ ppm:8.95 (s, 1H), 6.97 (s, 1H), 4.20 (q, J=7.2Hz, 2H), 1.24 (t, J=7.2Hz, 3H);
Carbon-13 nmr spectra (DMSO, 100MHz) δ ppm:164.28,163.88,158.80,91.05,60.34,14.81.
Embodiment 7
With 2-methylthio group-4-amino-5-ethyl formate thiazole 3 (10.0g, 45.9mmol) be dissolved in methyl alcohol (100mL) (can suitably heat with dissolving) fully, at room temperature, add iron powder (7.67g, 137.7mmol), (50mL 50mmol), has gas to produce in the reaction process slowly to drip 3N sulfuric acid or phosphoric acid solution again.Behind the room temperature reaction 16 hours, the thin-layer chromatography monitoring shows that raw material consumption finishes.Reaction solution is poured in the saturated sodium carbonate solution (500mL), add diatomite filtration, filtrate is used dichloromethane extraction (300mL * 2), merge organic phase and use the saturated common salt water washing again, anhydrous sodium sulfate drying, after removing by filter siccative, concentrated filtrate obtains 4 gram product 4-amino-5-ethyl formate thiazoles 4.(yield: 50%)
4.4-urea-5-ethyl formate thiazole 5 is synthetic
Embodiment 8
(1.50g 8.7mmol) is dissolved in tetrahydrofuran (THF) (50mL), and this solution is cooled to 0 ℃, and (1.88g 9.6mmol), stirred 1 hour down at 0 ℃ slowly to add trichloromethylchloroformate with 4-amino-5-ethyl formate thiazole 4.The saturated tetrahydrofuran solution (20mL) that adds ammonia then continues to stir 1 hour.Remove by filter the white solid of separating out, the crude product that mother liquor obtains after concentrating dissolves with ethyl acetate (200mL), water and saturated common salt water washing respectively, organic phase anhydrous sodium sulfate drying, remove by filter siccative, filtrate being spin-dried for obtains 1.59 gram product 4-urea-5-ethyl formate thiazoles 5.(yield: 85%)
Proton nmr spectra (DMS0,400MHz), δ ppm:9.26 (s, 1H), 8.68 (s, 1H), 7.50 (br, 2H), 4.30 (q, J=7.0Hz, 2H), 1.28 (t, J=7.0Hz, 3H);
Carbon-13 nmr spectra (DMS0,100MHz) δ ppm:162.67,158.80,155.28,153.12,99.82,61.32,14.07.
Embodiment 9
(1.50g 8.7mmol) is dissolved in methylene dichloride or toluene (50mL), and this solution is cooled to 0 ℃, and (2.8g 9.6mmol), stirred 1 hour down at 0 ℃ slowly to add triphosgene with 4-amino-5-ethyl formate thiazole 4.Add ammoniacal liquor or aqueous ammonium chloride solution (20mL) then, continue to stir 1 hour.Remove by filter the white solid of separating out, the crude product that mother liquor obtains after concentrating dissolves with ethyl acetate (200mL), water and saturated common salt water washing respectively, organic phase anhydrous sodium sulfate drying, remove by filter siccative, filtrate being spin-dried for obtains 0.6 gram product 4-urea-5-ethyl formate thiazole 5.(yield: 32%)
5.[4,5-d] and thiazole 5,7-dihydroxy-pyrimidine 6 synthetic
Embodiment 10
(1.00g 4.65mmol) is suspended in ethanol (30mL), adds 1N aqueous sodium hydroxide solution (4.7mL) with 4-urea-5-ethyl formate thiazole 5.This reaction solution is heated to 80 ℃, reacting after 2 hours, be cooled to 0 ℃, is that 5% salt acid for adjusting pH value is 6-7 with concentration expressed in percentage by weight, concentrate to remove and desolvate, the crude product that obtains dissolves with ethyl acetate (50mL), water and saturated common salt water washing respectively, organic phase anhydrous sodium sulfate drying, remove by filter siccative, filtrate concentrating obtains 0.59 gram product [4,5-d] thiazole 5,7-dihydroxy-pyrimidine 6.(yield: 75%)
Proton nmr spectra (DMSO, 400MHz), δ ppm:12.40 (s, 1H), 11.42 (s, 1H), 9.43 (s, 1H);
Carbon-13 nmr spectra (DMSO, 100MHz) δ ppm:162.40,158.74,157.38,151.26,104.67.
Embodiment 11
(1.00g 4.65mmol) is suspended in methyl alcohol (30mL), adds 2N potassium hydroxide aqueous solution (2.5mL) with 4-urea-5-ethyl formate thiazole 5.This reaction solution is heated to 100 ℃, reacting after 2 hours, be cooled to 0 ℃, is that 5% salt acid for adjusting pH value is 6-7 with concentration expressed in percentage by weight, concentrate to remove and desolvate, the crude product that obtains dissolves with ethyl acetate (50mL), water and saturated common salt water washing respectively, organic phase anhydrous sodium sulfate drying, remove by filter siccative, filtrate concentrating obtains 0.36 gram product [4,5-d] thiazole 5,7-dihydroxy-pyrimidine 6.(yield: 45%)
6.5,7-dichloro thiazole [4,5-d] pyrimidine 7 synthetic
Embodiment 12
With [4,5-d] thiazole 5, (0.50g 2.96mmol) joins in the phosphorus oxychloride (20mL) reflux 10 hours to 7-dihydroxy-pyrimidine 6.Phosphorus oxychloride is removed in careful then underpressure distillation, and the thick product that obtains is with ethyl acetate (50mL) dissolving, respectively with saturated sodium bicarbonate aqueous solution and salt solution washing.The organic phase anhydrous sodium sulfate drying filters out and is spin-dried for filtrate behind the siccative and obtains 0.50 gram product 5,7-dichloro thiazole [4,5-d] pyrimidine 7.(yield: 82%)
Proton nmr spectra (DMSO, 400MHz), δ ppm:10.08 (s, 1H);
1Carbon-13 nmr spectra (DMSO, 100MHz) δ ppm:171.03,169.16,156.36,156.02,126.25.
Embodiment 13
With [4,5-d] thiazole 5, (0.50g 2.96mmol) joins in sulfur oxychloride or the phosphorus pentachloride (20mL) reflux 10 hours to 7-dihydroxy-pyrimidine 6.Phosphorus oxychloride is removed in careful then underpressure distillation, and the thick product that obtains is with ethyl acetate (50mL) dissolving, respectively with saturated sodium bicarbonate aqueous solution and salt solution washing.The organic phase anhydrous sodium sulfate drying filters out and is spin-dried for filtrate behind the siccative and obtains 0.30 gram product 5,7-dichloro thiazole [4,5-d] pyrimidine 7.(yield: 49%).
Claims (7)
1.5 the synthetic method of 7-dichloro thiazole [4,5-d] pyrimidine may further comprise the steps:
The first step reaction is a raw material with the cyanamide, obtains cyano group imide dithio formic acid an alkali metal salt with dithiocarbonic anhydride and alkali metal hydroxide reaction; Generate corresponding monopotassium salt with methylating reagent reaction preference ground;
The reaction of second step, monopotassium salt are closed ring with ethyl bromoacetate and are generated 2-methylthio group-4-amino-5-ethyl formate thiazole under alkaline condition;
Three-step reaction, the methylthio group in 2-methylthio group-4-amino-5-ethyl formate thiazole obtain 4-amino-5-ethyl formate thiazole with going back the original reagent reduction under acidic conditions;
Four-step reaction, the amido in 4-amino-5-ethyl formate thiazole change into isocyanic ester earlier, generate corresponding 4-urea-5-ethyl formate thiazole with ammonia reagent again;
The reaction of the 5th step, 4-urea-5-ethyl formate thiazole are advanced-are gone on foot to close ring and obtain [4,5-d] thiazole 5,7-dihydroxy-pyrimidine under alkaline condition;
Six-step process, [4,5-d] thiazole 5,7-dihydroxy-pyrimidine and chlorinating agent reaction obtain the finished product 5,7-dichloro thiazole [4,5-d] pyrimidine.
2. according to claim 15, the synthetic method of 7-dichloro thiazole [4,5-d] pyrimidine is characterized in that the first step is reflected in the organic solvent carries out, and organic solvent is a kind of in methyl alcohol, ethanol or the ethyl acetate; Alkali metal hydroxide is with sodium hydroxide or potassium hydroxide; Methylating reagent is with methyl iodide or methyl-sulfate; The concentration expressed in percentage by weight 10～80% of alkali; Temperature of reaction is 0～40 ℃; Reaction times is 10～20 hours.
3. according to claim 15, the synthetic method of 7-dichloro thiazole [4,5-d] pyrimidine is characterized in that, second step was reflected in the organic solvent carries out, and organic solvent is a kind of in methyl alcohol, ethanol, ethyl acetate or the acetone; A kind of with in triethylamine, pyridine or the nitrogen methylmorpholine of alkali; Temperature of reaction is 0～80 ℃; Reaction times is 1～16 hour.
4. according to claim 15, the synthetic method of 7-dichloro thiazole [4,5-d] pyrimidine is characterized in that, the acid in the three-step reaction is a kind of in hydrochloric acid, sulfuric acid or the phosphoric acid; The concentration expressed in percentage by weight 10～50% of acid; Also original reagent is a kind of in zinc powder and the iron powder; Temperature of reaction is 0～40 ℃; Reaction times is 1～16 hour.
5. according to claim 15, the synthetic method of 7-dichloro thiazole [4,5-d] pyrimidine is characterized in that four-step reaction carries out in organic solvent, and organic solvent is a kind of in methylene dichloride, tetrahydrofuran (THF) or the toluene; Generate a kind of with in phosgene, trichloromethylchloroformate, triphosgene or the carbonyl dimidazoles of isocyanate compound; Ammonia reagent is a kind of in ammoniacal liquor, liquefied ammonia or the ammonium chloride; Temperature of reaction is 0～40 ℃; Reaction times is 1～16 hour.
6. according to claim 15, the synthetic method of 7-dichloro thiazole [4,5-d] pyrimidine is characterized in that, the 5th step was reflected in the organic solvent carries out, and organic solvent is methyl alcohol or ethanol; Alkali is with sodium hydroxide or potassium hydroxide; The concentration 10～80% of alkali concentration expressed in percentage by weight; Temperature of reaction is 0～100 ℃; Reaction times is 1～20 hour.
7. according to claim 15, the synthetic method of 7-dichloro thiazole [4,5-d] pyrimidine is characterized in that, the six-step process chlorinating agent is a kind of in phosphorus oxychloride, sulfur oxychloride or the phosphorus pentachloride; Temperature of reaction is 0～120 ℃; Reaction times is 1～20 hour.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009102018009A CN102060862A (en) | 2009-11-16 | 2009-11-16 | Synthesis method of 5,7-dichlorothiazole[4,5-d]pyrimidine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009102018009A CN102060862A (en) | 2009-11-16 | 2009-11-16 | Synthesis method of 5,7-dichlorothiazole[4,5-d]pyrimidine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102060862A true CN102060862A (en) | 2011-05-18 |
Family
ID=43996382
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009102018009A Pending CN102060862A (en) | 2009-11-16 | 2009-11-16 | Synthesis method of 5,7-dichlorothiazole[4,5-d]pyrimidine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102060862A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110372629A (en) * | 2019-08-23 | 2019-10-25 | 苏州络森生物科技有限公司 | A kind of synthetic method of 4- aminothiazole -5- carboxylic acid, ethyl ester |
-
2009
- 2009-11-16 CN CN2009102018009A patent/CN102060862A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110372629A (en) * | 2019-08-23 | 2019-10-25 | 苏州络森生物科技有限公司 | A kind of synthetic method of 4- aminothiazole -5- carboxylic acid, ethyl ester |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101613361B (en) | Method for preparing cefoxitin sodium | |
| CN101657462A (en) | The Preparation Method And Their Intermediate of capecitabine | |
| CN103373989B (en) | The preparation method of the intermediate of pazopanib hydrochloride | |
| CN114605328A (en) | Preparation method of 6-chloro-2-methyl-2H-indazole-5-amine | |
| CN112778303A (en) | Preparation method of CDK4/6 kinase inhibitor SHR6390 | |
| CN102746211B (en) | Method for preparing substituted indole-3-methanal compound | |
| CN106397516B (en) | Cangrelor intermediate and its preparation method and application | |
| ES2543643T3 (en) | Asymmetric reduction process | |
| CN102060862A (en) | Synthesis method of 5,7-dichlorothiazole[4,5-d]pyrimidine | |
| CN103936759A (en) | Simple preparation method for (3aS,6aR)-1,3-dibenzyl-tetrahydro-4H-thieno[3,4-d]imidazole-2,4-(1H)-dione | |
| CN111620808A (en) | 2-aldehyde indole compound and preparation method thereof | |
| CN106478587A (en) | A kind of synthetic method of ticagrelor intermediate | |
| CN106008459A (en) | Trelagliptin preparation method | |
| CN110551144A (en) | Preparation method of amoxicillin | |
| CN101323602A (en) | 2-oxazoline derivates and method for preparing the same | |
| CN101735242B (en) | Method for preparing D-(+)-biotin intermediate | |
| CN104761557B (en) | Hexahydro-1H-pyrrolo[3,4-d]pyrimidine compound and preparation method thereof | |
| CN103319480B (en) | One prepares the method for 2,3,4,9-tetrahydro-beta-carboline-1-ketone | |
| CN106045995A (en) | Synthesizing method of 5-bromine-1H-pyrrolo[2,3-b]pyridine | |
| CN102432616B (en) | Method for preparing L-prolinamide and intermediate thereof | |
| CN101880285B (en) | Method for synthetizing allyl-substituted camptothecin compound | |
| CN100376546C (en) | Diethyl 4(4-oxobutyl) benzoyl-L-glutamate and its preparation and use | |
| CN101935317B (en) | Synthesizing method of 2-methyl-7-(substituted pyrimidine-4-amino)-4-(substituted piperazine-1-base) piperidine-1-base) isoindoline-1-ketone and intermediate thereof | |
| CN112979564A (en) | Preparation method of sitagliptin intermediate | |
| CN103130799A (en) | Preparing method of 2-hydroxy pyridino-6,7,8,9-tetrahydro-5H- pyridine[2,3-d] azepine derivative |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20110518 |