CN113620977B - Synthesis method of thiazolopyrimidinone acetic acid - Google Patents
Synthesis method of thiazolopyrimidinone acetic acid Download PDFInfo
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- CN113620977B CN113620977B CN202110975358.6A CN202110975358A CN113620977B CN 113620977 B CN113620977 B CN 113620977B CN 202110975358 A CN202110975358 A CN 202110975358A CN 113620977 B CN113620977 B CN 113620977B
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 title claims abstract description 58
- AKDQOJPOLRMVMF-UHFFFAOYSA-N [1,3]thiazolo[5,4-d]pyrimidine 3-oxide Chemical compound N1=CN=C2S(=O)C=NC2=C1 AKDQOJPOLRMVMF-UHFFFAOYSA-N 0.000 title claims description 10
- 238000001308 synthesis method Methods 0.000 title claims description 5
- 229960000583 acetic acid Drugs 0.000 claims abstract description 21
- 150000001875 compounds Chemical class 0.000 claims abstract description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 17
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims abstract description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims abstract description 16
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims abstract description 16
- 238000000034 method Methods 0.000 claims abstract description 12
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims abstract description 10
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims abstract description 10
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229910000104 sodium hydride Inorganic materials 0.000 claims abstract description 10
- 239000012312 sodium hydride Substances 0.000 claims abstract description 10
- 239000012362 glacial acetic acid Substances 0.000 claims abstract description 8
- 229940098779 methanesulfonic acid Drugs 0.000 claims abstract description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000002904 solvent Substances 0.000 claims abstract description 7
- 239000002994 raw material Substances 0.000 claims abstract description 3
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 claims abstract 6
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims abstract 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 33
- 238000006243 chemical reaction Methods 0.000 claims description 27
- DKMROQRQHGEIOW-UHFFFAOYSA-N Diethyl succinate Chemical compound CCOC(=O)CCC(=O)OCC DKMROQRQHGEIOW-UHFFFAOYSA-N 0.000 claims description 9
- LHHLYOVYBZWIGM-UHFFFAOYSA-N diethyl 2-formylbutanedioate Chemical compound CCOC(=O)CC(C=O)C(=O)OCC LHHLYOVYBZWIGM-UHFFFAOYSA-N 0.000 claims description 8
- REGFWZVTTFGQOJ-UHFFFAOYSA-N 4,5-dihydro-1,3-thiazol-2-amine Chemical compound NC1=NCCS1 REGFWZVTTFGQOJ-UHFFFAOYSA-N 0.000 claims description 7
- 238000010189 synthetic method Methods 0.000 claims description 6
- 230000002194 synthesizing effect Effects 0.000 abstract description 7
- -1 thiazolidine pyrimidone acetic acid Chemical compound 0.000 abstract description 7
- 238000009776 industrial production Methods 0.000 abstract description 2
- OBTZDIRUQWFRFZ-UHFFFAOYSA-N 2-(5-methylfuran-2-yl)-n-(4-methylphenyl)quinoline-4-carboxamide Chemical compound O1C(C)=CC=C1C1=CC(C(=O)NC=2C=CC(C)=CC=2)=C(C=CC=C2)C2=N1 OBTZDIRUQWFRFZ-UHFFFAOYSA-N 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 150000002391 heterocyclic compounds Chemical class 0.000 description 4
- 125000000623 heterocyclic group Chemical group 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 238000010791 quenching Methods 0.000 description 3
- 230000000171 quenching effect Effects 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-ZSJDYOACSA-N Heavy water Chemical group [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000006783 Fischer indole synthesis reaction Methods 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 238000005614 Skraup synthesis reaction Methods 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a method for synthesizing thiazolidine pyrimidone acetic acid, which comprises the following specific steps: (1) The compound II is used as a raw material, tetrahydrofuran is used as a solvent, and reacts with ethyl formate under the action of sodium hydride to generate a compound III; (2) Reacting the compound III with the compound V in absolute ethyl alcohol to generate a compound IV; (3) The compound IV reacts with methanesulfonic acid in glacial acetic acid to generate thiazolidinopyrimidinone acetic acid, namely the compound I. The method is simple to operate, has higher yield, is suitable for industrial production, and fills the obtaining way of the condensed-ring compound.
Description
Technical Field
The invention relates to the field of organic synthesis, in particular to a method for synthesizing thiazolidinopyrimidinone acetic acid ((7-oxo-2, 3-dihydro-7H-thiazolo [3,2-a ] pyrimidin-6-yl) -acetic acid).
Background
The condensed heterocyclic compounds are important organic compounds, refer to compounds in which benzene rings are condensed with heterocycles or the heterocycles are condensed together, and are important components in pharmaceutical chemistry research. The condensed heterocyclic compounds are various in species, complex in structure, and most commonly include quinoline, indole, purine and the like. Due to the structural complexity of fused heterocyclic compounds, the synthetic methods are also different. Relatively speaking, common condensed heterocyclic compounds, such as quinoline and indole, have been studied in a large number, and various classical synthetic methods, such as Skraup quinoline synthesis, fischer indole synthesis and the like, have also been developed. However, there are few reports of synthetic methods for the specific structure of thiazolopyrimidinones.
Disclosure of Invention
Aiming at the problems existing in the prior art, the invention aims to provide a method for synthesizing thiazolidinopyrimidinone acetic acid. The method is simple to operate, has higher yield, is suitable for industrial production, and fills the obtaining way of the condensed-ring compound.
The technical scheme adopted by the invention is as follows:
a method for synthesizing thiazolopyrimidinone acetic acid, which is carried out according to the following flow:
the method comprises the following specific steps:
(1) Diethyl succinate (compound II) is used as a raw material, tetrahydrofuran is used as a solvent, and reacts with ethyl formate under the action of sodium hydride to generate diethyl 2-formyl succinate, namely a compound III;
(2) Reacting the compound III with 2-aminothiazoline (compound V) in absolute ethyl alcohol to generate thiazolidinopyrimidinone ethyl acetate, namely a compound IV;
(3) The compound IV reacts with methanesulfonic acid in glacial acetic acid to generate thiazolidinopyrimidinone acetic acid, namely the compound I.
In the step (1), the molar ratio of diethyl succinate, sodium hydride and ethyl formate is 1:1.1-1.5:1.2-1.8, preferably 1:1.2:1.5.
In the step (1), the sodium hydride content is 60%; the volume amount of tetrahydrofuran is 8 to 12 times, preferably 10 times, that of diethyl succinate.
In the step (1), ethyl formate is dripped at the temperature of-2 ℃ to 2 ℃, preferably 0 ℃, and reacts for 8 to 12 hours at room temperature after dripping; preferably at 25℃for 10h.
In step (2), the molar ratio of 2-aminothiazoline to compound III is 1:1.2-1.6, preferably 1:1.5.
In step (2), the volume amount of absolute ethanol is 8 to 12 times, preferably 10 times that of the compound III.
In the step (2), the reaction conditions are as follows: the reaction is carried out at 78℃for 15-18h, preferably 16h.
In step (3), the molar ratio of compound IV to methanesulfonic acid is 1:1.2-1.5, preferably 1:1.3.
In step (3), the volume amount of glacial acetic acid is 4 to 5 times, preferably 4 times that of the compound IV.
In the step (3), the reaction conditions are as follows: the reaction is carried out at 115-125℃for 15-18h, preferably 16h.
The beneficial technical effects of the invention are as follows:
the invention provides a feasible synthesis method, wherein carboxyl functional groups carried in the molecular structure of a target compound are convenient to connect the fused heterocyclic fragment with active molecular mother nucleus on one hand, more potential compounds with pharmacological activity are created, and on the other hand, functional groups can be converted through other chemical reactions to obtain a series of small molecule synthesis building blocks with the fused heterocyclic fragment, which are used in pharmaceutical chemistry research.
Drawings
FIG. 1 is a nuclear magnetic resonance hydrogen spectrum of the compound I prepared in example 1 of the present invention.
Detailed Description
The present invention will be described in detail below with reference to the drawings and examples.
Example 1:
a method for synthesizing thiazolopyrimidinone acetic acid comprises the following specific steps:
step (1): under the protection of nitrogen, 697g (4.0 mol) of diethyl succinate (compound II) and 7.0L of tetrahydrofuran are added into a reaction bottle, stirring is started, the temperature is reduced to 0 ℃, 192g (60 percent, 4.8 mol) of sodium hydride is added in batches, after the addition, the reaction is carried out for 1 hour at room temperature, the temperature is reduced to 0 ℃, 444g (6.0 mol) of ethyl formate is slowly dripped into the reaction bottle, the reaction is stirred for 10 hours at room temperature after the dripping, 200mL of water quenching reaction is added, diluted hydrochloric acid is added to adjust the pH to 5-6, the extraction is carried out for 3 times by 5L of ethyl acetate, the organic phases are combined, the mixture is washed by saturated saline, and 600g of diethyl 2-formylsuccinate (compound III) is obtained after drying and concentration.
Step (2): to the reaction flask was added 303g (1.50 mol) of diethyl 2-formyl succinate (compound III), 102g (1.00 mol) of 2-aminothiazoline (compound V), 3.0L of absolute ethyl alcohol, heating to 78 ℃ for 16 hours, cooling to room temperature, filtering, concentrating the filtrate to dryness, adding 500mL of ethyl acetate and recrystallizing to obtain 285g of thiazolopyrimidinone ethyl acetate (compound IV).
Step (3): 240g (1.0 mol) of ethyl azolidinopyrimidinone acetate (compound IV), 125g (1.3 mol) of methanesulfonic acid, 960mL of glacial acetic acid, heating to 118 ℃ for 16 hours, concentrating the solvent under reduced pressure, adding 300mL of ethanol, and recrystallizing to obtain 145g of thiazolidinopyrimidinone acetic acid (compound I).
As shown in FIG. 1, it can be seen from FIG. 1 that Shan Qingfeng, which is a chemical shift of 7.76ppm, corresponds to aromatic hydrogen on pyrimidine ring, that the dihydride triplet, which is a chemical shift of 4.46ppm, corresponds to methylene linked to sulfur atom, that the dihydride triplet, which is a chemical shift of 3.56ppm, corresponds to methylene linked to nitrogen atom, that the dihydride singlet, which is a chemical shift of 3.45ppm, corresponds to methylene linked to carboxyl group, and that in addition, carboxyl hydrogen does not appear because the nuclear magnetic solvent is heavy water.
Example 2:
a method for synthesizing thiazolopyrimidinone acetic acid comprises the following specific steps:
step (1): under the protection of nitrogen, 69.7g (0.40 mol) of diethyl succinate (compound II) and 836mL of tetrahydrofuran are added into a reaction bottle, stirring is started, the temperature is reduced to-2 ℃, 24g (60 percent, 0.60 mol) of sodium hydride is added in batches, after the addition, the reaction is carried out for 1 hour at room temperature, the temperature is reduced to-2 ℃, 53.3g (0.72 mol) of ethyl formate is slowly dripped into the reaction bottle, the reaction is stirred for 8 hours at room temperature after the dripping, 25mL of water quenching reaction is added, diluted hydrochloric acid is added to adjust the pH to 5-6, the ethyl acetate is used for 500mL for extraction for 3 times, the organic phases are combined, the mixture is washed with saturated saline, and 58g of diethyl 2-formylsuccinate (compound III) is obtained after drying and concentration.
Step (2): to the reaction flask was added 32.3g (0.16 mol) of diethyl 2-formyl succinate (compound III), 10.2g (0.10 mol) of 2-aminothiazoline (compound V), 388mL of absolute ethyl alcohol, heated to 78℃for 15 hours, cooled to room temperature, filtered, the filtrate was concentrated to dryness, and 50mL of ethyl acetate was added to recrystallize to obtain 24.6g of thiazolopyrimidinone ethyl acetate (compound IV).
Step (3): into the reaction flask was added 24g (0.10 mol) of ethyl azolidinopyrimidinone acetate (compound IV), 14.4g (0.15 mol) of methanesulfonic acid, 120mL of glacial acetic acid, heating to 118℃for 15 hours, concentrating the solvent under reduced pressure, adding 30mL of ethanol, and recrystallizing to obtain 12.8g of thiazolidinopyrimidinone acetic acid (compound I).
Example 3:
a method for synthesizing thiazolopyrimidinone acetic acid comprises the following specific steps:
step (1): under the protection of nitrogen, 69.7g (0.40 mol) of diethyl succinate (compound II) and 552mL of tetrahydrofuran are added into a reaction bottle, stirring is started, the temperature is reduced to 2 ℃, 17.6g (60 percent, 0.44 mol) of sodium hydride is added in batches, after the addition, the reaction is carried out for 1 hour at room temperature, the temperature is reduced to 2 ℃, 35.5g (0.48 mol) of ethyl formate is slowly dripped into the reaction bottle, the reaction is stirred for 12 hours at room temperature after the dripping, 20mL of water quenching reaction is added, diluted hydrochloric acid is added to adjust the pH to 5-6, the ethyl acetate is used for 500mL extraction for 3 times, the organic phases are combined, the mixture is washed with saturated saline, and the mixture is dried and concentrated to obtain 54.4g of diethyl 2-formylsuccinate (compound III).
Step (2): to the reaction flask was added 24.2g (0.12 mol) of diethyl 2-formyl succinate (compound III), 10.2g (0.10 mol) of 2-aminothiazoline (compound V), 194mL of absolute ethyl alcohol, heated to 78℃for 18 hours, cooled to room temperature, filtered, the filtrate was concentrated to dryness, and 50mL of ethyl acetate was added to recrystallize to obtain 18.6g of thiazolopyrimidinone ethyl acetate (compound IV).
Step (3): into the reaction flask was added 24g (0.10 mol) of ethyl azolidinopyrimidinone acetate (compound IV), 11.5g (0.12 mol) of methanesulfonic acid, 96mL of glacial acetic acid, heating to 118℃for 18 hours, concentrating the solvent under reduced pressure, adding 30mL of ethanol, and recrystallizing to obtain 12.5g of thiazolidinopyrimidinone acetic acid (compound I).
Claims (6)
1. The synthesis method of the thiazolopyrimidinone acetic acid is characterized by comprising the following steps of:
the method comprises the following specific steps:
(1) Diethyl succinate (compound II) is used as a raw material, tetrahydrofuran is used as a solvent, and reacts with ethyl formate under the action of sodium hydride to generate diethyl 2-formyl succinate, namely a compound III;
(2) Reacting the compound III with 2-aminothiazoline (compound V) in absolute ethyl alcohol to generate thiazolidinopyrimidinone ethyl acetate, namely a compound IV;
(3) Reacting the compound IV with methanesulfonic acid in glacial acetic acid to generate thiazolidinopyrimidinone acetic acid, namely a compound I;
in the step (2), the volume amount of the absolute ethyl alcohol is 8-12 times that of the compound III; the reaction conditions are as follows: reacting for 15-18h at 78 ℃;
in the step (3), the volume amount of glacial acetic acid is 4-5 times that of the compound IV; the reaction conditions are as follows: reacting for 15-18h at 115-125 ℃.
2. The method according to claim 1, wherein in the step (1), the molar ratio of diethyl succinate, sodium hydride and ethyl formate is 1:1.1-1.5:1.2-1.8.
3. The synthetic method of claim 1 wherein in step (1), the sodium hydride content is 60%; the volume amount of tetrahydrofuran is 8-12 times of that of diethyl succinate.
4. The synthesis method according to claim 1, wherein in the step (1), the ethyl formate is added dropwise at a temperature of-2 ℃ to 2 ℃ and reacted at room temperature for 8 to 12 hours after the completion of the dropping.
5. The synthetic method according to claim 1, wherein in step (2), the molar ratio of 2-aminothiazoline to compound III is 1:1.2-1.6.
6. The synthetic method according to claim 1, wherein in step (3), the molar ratio of compound IV to methanesulfonic acid is 1:1.2-1.5.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103534241A (en) * | 2011-02-17 | 2014-01-22 | 癌症疗法Crc私人有限公司 | Fak inhibitor |
| CN103709126A (en) * | 2013-11-14 | 2014-04-09 | 江苏中旗作物保护股份有限公司 | Synthetic method of pesticide dinotefuran intermediate 3-hydroxymethyl tetrahydrofuran |
| CN104507481A (en) * | 2012-05-23 | 2015-04-08 | 萨维拉制药有限公司 | 7-oxo-4,7 -dihydro- pyrazolo [1, 5 -a] pyrimidine derivatives which are useful in the treatment, amelioration or prevention of a viral disease |
-
2021
- 2021-08-24 CN CN202110975358.6A patent/CN113620977B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103534241A (en) * | 2011-02-17 | 2014-01-22 | 癌症疗法Crc私人有限公司 | Fak inhibitor |
| CN104507481A (en) * | 2012-05-23 | 2015-04-08 | 萨维拉制药有限公司 | 7-oxo-4,7 -dihydro- pyrazolo [1, 5 -a] pyrimidine derivatives which are useful in the treatment, amelioration or prevention of a viral disease |
| CN103709126A (en) * | 2013-11-14 | 2014-04-09 | 江苏中旗作物保护股份有限公司 | Synthetic method of pesticide dinotefuran intermediate 3-hydroxymethyl tetrahydrofuran |
Non-Patent Citations (1)
| Title |
|---|
| Synthesis of 2,3- Dihydrothiazolo[3,2-c]pyrimidines;Brown, George R.;Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry(第18期);2022-2024 * |
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