CN115417875A - Synthesis method of 5,8-dimethoxy- [1,2,4] triazolo [1,5-C ] pyrimidine-2-amine - Google Patents
Synthesis method of 5,8-dimethoxy- [1,2,4] triazolo [1,5-C ] pyrimidine-2-amine Download PDFInfo
- Publication number
- CN115417875A CN115417875A CN202211136529.7A CN202211136529A CN115417875A CN 115417875 A CN115417875 A CN 115417875A CN 202211136529 A CN202211136529 A CN 202211136529A CN 115417875 A CN115417875 A CN 115417875A
- Authority
- CN
- China
- Prior art keywords
- dimethoxy
- carried out
- stirring
- triazolo
- amine
- 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
- DBJPBHJHAPAUQU-UHFFFAOYSA-N 5,8-dimethoxy-[1,2,4]triazolo[1,5-c]pyrimidin-2-amine Chemical compound COC1=CN=C(OC)N2N=C(N)N=C12 DBJPBHJHAPAUQU-UHFFFAOYSA-N 0.000 title claims abstract description 24
- 238000001308 synthesis method Methods 0.000 title abstract description 10
- 238000000034 method Methods 0.000 claims abstract description 17
- 239000002904 solvent Substances 0.000 claims abstract description 11
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 9
- 238000005576 amination reaction Methods 0.000 claims abstract description 5
- 238000007363 ring formation reaction Methods 0.000 claims abstract description 5
- 239000003513 alkali Substances 0.000 claims abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 36
- JIADELSANNMYFC-UHFFFAOYSA-N 5-methoxypyrimidine Chemical compound COC1=CN=CN=C1 JIADELSANNMYFC-UHFFFAOYSA-N 0.000 claims description 30
- 238000003756 stirring Methods 0.000 claims description 30
- 238000001914 filtration Methods 0.000 claims description 24
- 239000007787 solid Substances 0.000 claims description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 18
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 238000001816 cooling Methods 0.000 claims description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 238000010992 reflux Methods 0.000 claims description 12
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 7
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 7
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 7
- 239000004202 carbamide Substances 0.000 claims description 7
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 6
- 229940040526 anhydrous sodium acetate Drugs 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 238000000926 separation method Methods 0.000 claims description 5
- 230000002194 synthesizing effect Effects 0.000 claims description 5
- JEARLRMCZMBVFC-UHFFFAOYSA-N 2,5-dimethoxy-1h-pyrimidin-6-one Chemical compound COC1=CN=C(OC)N=C1O JEARLRMCZMBVFC-UHFFFAOYSA-N 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 4
- 230000006837 decompression Effects 0.000 claims description 3
- KEAYESYHFKHZAL-OUBTZVSYSA-N sodium-24 Chemical compound [24Na] KEAYESYHFKHZAL-OUBTZVSYSA-N 0.000 claims description 3
- 238000001704 evaporation Methods 0.000 claims 1
- 238000005406 washing Methods 0.000 claims 1
- 238000010189 synthetic method Methods 0.000 abstract description 6
- 230000002363 herbicidal effect Effects 0.000 abstract description 5
- 239000004009 herbicide Substances 0.000 abstract description 5
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- 230000003321 amplification Effects 0.000 abstract description 4
- 231100000481 chemical toxicant Toxicity 0.000 abstract description 4
- 238000003199 nucleic acid amplification method Methods 0.000 abstract description 4
- 239000003440 toxic substance Substances 0.000 abstract description 4
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- VOVYJRTWCHAHQC-UHFFFAOYSA-N 5-methoxypyrimidine Chemical compound COC1=CN=C=N[CH]1 VOVYJRTWCHAHQC-UHFFFAOYSA-N 0.000 abstract 4
- 238000002360 preparation method Methods 0.000 abstract 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 8
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 238000005660 chlorination reaction Methods 0.000 description 3
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 2
- 241000209094 Oryza Species 0.000 description 2
- 235000007164 Oryza sativa Nutrition 0.000 description 2
- 239000005592 Penoxsulam Substances 0.000 description 2
- SYJGKVOENHZYMQ-UHFFFAOYSA-N Penoxsulam Chemical compound N1=C2C(OC)=CN=C(OC)N2N=C1NS(=O)(=O)C1=C(OCC(F)F)C=CC=C1C(F)(F)F SYJGKVOENHZYMQ-UHFFFAOYSA-N 0.000 description 2
- 231100000086 high toxicity Toxicity 0.000 description 2
- 238000006698 hydrazinolysis reaction Methods 0.000 description 2
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 235000009566 rice Nutrition 0.000 description 2
- 238000006798 ring closing metathesis reaction Methods 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 230000017105 transposition Effects 0.000 description 2
- MUDVUWOLBJRUGF-UHFFFAOYSA-N (c-methoxycarbonimidoyl)azanium;chloride Chemical compound Cl.COC(N)=N MUDVUWOLBJRUGF-UHFFFAOYSA-N 0.000 description 1
- SADHVOSOZBAAGL-UHFFFAOYSA-N 3-(trifluoromethoxy)aniline Chemical compound NC1=CC=CC(OC(F)(F)F)=C1 SADHVOSOZBAAGL-UHFFFAOYSA-N 0.000 description 1
- KELXHQACBIUYSE-UHFFFAOYSA-N 5-methoxy-1h-pyrimidine-2,4-dione Chemical compound COC1=CNC(=O)NC1=O KELXHQACBIUYSE-UHFFFAOYSA-N 0.000 description 1
- VTKRSTQMGNRMHL-UHFFFAOYSA-N amino 4-nitrobenzoate Chemical compound NOC(=O)C1=CC=C([N+]([O-])=O)C=C1 VTKRSTQMGNRMHL-UHFFFAOYSA-N 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229960000789 guanidine hydrochloride Drugs 0.000 description 1
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 1
- IIXGBDGCPUYARL-UHFFFAOYSA-N hydroxysulfamic acid Chemical compound ONS(O)(=O)=O IIXGBDGCPUYARL-UHFFFAOYSA-N 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 description 1
- NORABPMBUQMZLT-UHFFFAOYSA-N n-hydroxy-4-nitrobenzamide Chemical compound ONC(=O)C1=CC=C([N+]([O-])=O)C=C1 NORABPMBUQMZLT-UHFFFAOYSA-N 0.000 description 1
- WRIZJEREXIDJCC-UHFFFAOYSA-N oosponol Chemical compound C1=CC=C2C(C(=O)CO)=COC(=O)C2=C1O WRIZJEREXIDJCC-UHFFFAOYSA-N 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000009333 weeding Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Abstract
The invention relates to the technical field of herbicide production, and particularly relates to a synthetic method of 5,8-dimethoxy- [1,2,4] triazolo [1,5-C ] pyrimidine-2-amine. The preparation method comprises the steps of adding a solvent, alkali and an amination reagent into 2.5-dimethoxy-4-hydroxypyrimidine to prepare 3-amino-2.5-methoxypyrimidine (3H) -4-ketone, and then adding a cyclization reagent into 3-amino-2.5-methoxypyrimidine (3H) -4-ketone to prepare 5,8-dimethoxy- [1,2,4] triazolo [1,5-C ] pyrimidin-2-amine. The invention adopts a brand new two-step synthesis method, has short steps, avoids using highly toxic chemicals in the synthesis process, and is a safe and controllable synthesis method suitable for amplification.
Description
Technical Field
The invention relates to the technical field of herbicide production, and particularly relates to a synthetic method of 5,8-dimethoxy- [1,2,4] triazolo [1,5-C ] pyrimidine-2-amine.
Background
5,8-dimethoxy- [1,2,4] triazolo [1,5-C ] pyrimidin-2-amine is an important raw material for the herbicide penoxsulam. Penoxsulam has the characteristics of high efficiency, low toxicity, safety and low volatility, and is particularly suitable for application in rice. The herbicide is safe to use for rice crops and high in weeding efficiency, and is developed into an extremely important herbicide product nowadays. Currently, there are three major industrial processes for the production of 5,8-dimethoxy- [1,2,4] triazolo [1,5-C ] pyrimidin-2-amine.
The method comprises the following steps:
the 2, 5-dimethoxy-4-hydroxypyrimidine is used as a raw material, and a product is obtained through chlorination, hydrazinolysis, ring closure and transposition, and the main problems are high toxicity and high price of hydrogen bromide.
The second method comprises the following steps:
2, 4-dihydroxy-5-methoxyl pyrimidine is used as a raw material, and the product is obtained through chlorination, hydrazinolysis, ring closure and substitution transposition. Similar to the method, the method is also limited by the high toxicity and high price of hydrogen bromide.
The third method comprises the following steps:
the 2.4-dihydroxy-5-methoxypyrimidine is used as a raw material, and a product is obtained through the steps of chlorination, ammoniation, substitution, ring closing and the like, so that hydrogen bromide is avoided being used, but hydrogen sulfide with strong toxicity and stink can be generated in the ring closing step.
The three methods described above each have advantages and also each have disadvantages. In the first method and the second method, virulent hydrogen bromide is needed, virulent and malodorous hydrogen sulfide is generated in the third method, and great potential safety hazards are generated in the production process.
Disclosure of Invention
Aiming at the problems in the background art, provides 5,8-dimethoxy- [1,2,4] triazolo
A synthetic method of [1,5-C ] pyrimidine-2-amine. The invention adopts a brand new synthesis method, has short steps, avoids using highly toxic chemicals, and is a safe and controllable synthesis method suitable for amplification.
The invention provides a synthetic method of 5,8-dimethoxy- [1,2,4] triazolo [1,5-C ] pyrimidine-2-amine, which comprises the following steps:
adding a solvent, an alkali and an amination reagent into 2.5-dimethoxy-4-hydroxypyrimidine to prepare 3-amino-2.5-methoxypyrimidine (3H) -4-ketone, and adding a cyclization reagent into 3-amino-2.5-methoxypyrimidine (3H) -4-ketone to prepare 5,8-dimethoxy- [1,2,4] triazolo [1,5-C ] pyrimidin-2-amine.
S1, 90-110 g of 2.5-dimethoxy-4-hydroxypyrimidine is added into 1.5-2.5L of anhydrous DMF, 270-290 g of anhydrous cesium carbonate is added, nitrogen protection is carried out, stirring is carried out for 1 hour at room temperature, then 170-190 g of O-2,4,6-trimethylbenzenesulfonylhydroxylamine is added, stirring is carried out for 6 hours at room temperature, then heating is carried out to 50 ℃, stirring is carried out for 5 hours, cooling is carried out to 10 ℃, filtering is carried out, 4-6L of water and 0.5-1.5L of ethyl acetate are added, stirring is carried out for 30 minutes, liquid separation is carried out, the ethyl acetate layer is washed once by 190-210 ml of water, and decompression is carried out to remove the solvent to obtain a light yellow solid, namely 3-amino-2.5-methoxypyrimidine (3H) -4-one;
s2, taking the product 3-amino-2, 5-methoxypyrimidine (3H) -4-ketone in the first step, adding the product into 560 to 650 milliliters of acetonitrile, adding 20 to 30 grams of urea, 27 to 29 grams of anhydrous sodium acetate and 24 to 26 grams of acetic acid, refluxing for 8 hours, cooling to 10 ℃, filtering, adding the solid into 290 to 310 grams of water, stirring for 30 minutes, filtering, adding 290 to 310 milliliters of methanol into the obtained light yellow solid, refluxing for 1 hour, cooling to 10 ℃, filtering, and drying the obtained white-like solid to obtain 5,8-dimethoxy- [1,2,4] triazolo [1,5-C ] pyrimidin-2-amine.
Preferably, the synthesis method of 5,8-dimethoxy- [1,2,4] triazolo [1,5-C ] pyrimidin-2-amine comprises the following steps:
s1, 100 g of 2, 5-dimethoxy-4-hydroxypyrimidine is added into 2L of anhydrous DMF, 280 g of anhydrous cesium carbonate is added, nitrogen protection is carried out, stirring is carried out for 1 hour at room temperature, 180 g of O-2,4,6-trimethylbenzenesulfonylhydroxylamine is added, stirring is carried out for 6 hours at room temperature, then the temperature is increased to 50 ℃, stirring is carried out for 5 hours, the temperature is reduced to 10 ℃, filtering is carried out, 5L of water and 1L of ethyl acetate are added, stirring is carried out for 30 minutes, liquid separation is carried out, the ethyl acetate layer is washed once by 200 ml of water, and the solvent is evaporated under reduced pressure to obtain a light yellow solid;
s2, taking 60 g of the product 3-amino-2, 5-methoxypyrimidine (3H) -4-ketone in the first step, adding the product into 600 ml of acetonitrile, adding 25 g of urea, 28 g of anhydrous sodium acetate and 25 g of acetic acid, refluxing for 8 hours, cooling to 10 ℃, filtering, adding the solid into 300 g of water, stirring for 30 minutes, filtering, adding 300 ml of methanol into the obtained light yellow solid, refluxing for 1 hour, cooling to 10 ℃, filtering, and drying the obtained white-like solid to obtain 5,8-dimethoxy- [1,2,4] triazolo [1,5-C ] pyrimidin-2-amine.
Compared with the prior art, the invention has the following beneficial technical effects: the invention adopts a brand new two-step synthesis method, has short steps, avoids using highly toxic chemicals in the synthesis process, and is a safe and controllable synthesis method suitable for amplification.
Detailed Description
Example one
The invention provides a method for synthesizing 5,8-dimethoxy- [1,2,4] triazolo [1,5-C ] pyrimidine-2-amine, which comprises the following steps:
adding a solvent, an alkali and an amination reagent into 2.5-dimethoxy-4-hydroxypyrimidine to prepare 3-amino-2.5-methoxypyrimidine (3H) -4-ketone, and adding a cyclization reagent into 3-amino-2.5-methoxypyrimidine (3H) -4-ketone to prepare 5,8-dimethoxy- [1,2,4] triazolo [1,5-C ] pyrimidin-2-amine.
Further, the amination reagent may be O-2,4,6-trimethylbenzenesulfonylhydroxylamine, hydroxylamine sulfonic acid, phenylphosphonylhydroxylamine, O-p-nitrobenzoylhydroxylamine, O-2, 4-nitrobenzoylhydroxylamine, or the like. The base can be anhydrous cesium carbonate, potassium carbonate, sodium tert-butoxide, potassium tert-butoxide, sodium hydrogen, potassium hydroxide, etc. The solvent used may be DMF, DMSO, THF, etc. The cyclization agent can be urea, O-methylisourea hydrochloride, O-methylisourea sulfate, guanidine hydrochloride, etc.
Example two
The invention provides a method for synthesizing 5,8-dimethoxy- [1,2,4] triazolo [1,5-C ] pyrimidine-2-amine, which comprises the following steps
S1, 90-110 g of 2.5-dimethoxy-4-hydroxypyrimidine is added into 1.5-2.5L of anhydrous DMF, 270-290 g of anhydrous cesium carbonate is added, nitrogen protection is carried out, stirring is carried out for 1 hour at room temperature, then 170-190 g of O-2,4,6-trimethylbenzenesulfonylhydroxylamine is added, stirring is carried out for 6 hours at room temperature, then heating is carried out to 50 ℃, stirring is carried out for 5 hours, cooling is carried out to 10 ℃, filtering is carried out, 4-6L of water and 0.5-1.5L of ethyl acetate are added, stirring is carried out for 30 minutes, liquid separation is carried out, the ethyl acetate layer is washed once by 190-210 ml of water, and decompression is carried out to remove the solvent to obtain a light yellow solid, namely 3-amino-2.5-methoxypyrimidine (3H) -4-one;
s2, taking 60 g of the product 3-amino-2, 5-methoxypyrimidine (3H) -4-ketone in the first step, adding the product into 560 to 650 ml of acetonitrile, adding 20 to 30 g of urea, 27 to 29 g of anhydrous sodium acetate and 24 to 26 g of acetic acid, refluxing for 8 hours, cooling to 10 ℃, filtering, adding the solid into 290 to 310 g of water, stirring for 30 minutes, filtering, adding 290 to 310 ml of methanol into the obtained light yellow solid, refluxing for 1 hour, cooling to 10 ℃, filtering, and drying the obtained white-like solid to obtain 5,8-dimethoxy- [1,2,4] triazolo [1,5-C ] pyrimidin-2-amine.
EXAMPLE III
The invention provides a synthetic method of 5,8-dimethoxy- [1,2,4] triazolo [1,5-C ] pyrimidine-2-amine, which comprises the following steps:
s1, 100 g of 2, 5-dimethoxy-4-hydroxypyrimidine is added into 2L of anhydrous DMF, 280 g of anhydrous cesium carbonate is added, nitrogen protection is carried out, stirring is carried out for 1 hour at room temperature, 180 g of O-2,4,6-trimethylbenzenesulfonylhydroxylamine is added, stirring is carried out for 6 hours at room temperature, then the temperature is increased to 50 ℃, stirring is carried out for 5 hours, the temperature is reduced to 10 ℃, filtering is carried out, 5L of water and 1L of ethyl acetate are added, stirring is carried out for 30 minutes, liquid separation is carried out, the ethyl acetate layer is washed once by 200 ml of water, and the solvent is evaporated under reduced pressure to obtain 81 g of light yellow solid;
s2, taking 60 g of the product 3-amino-2, 5-methoxypyrimidine (3H) -4-ketone in the first step, adding the product into 600 ml of acetonitrile, adding 25 g of urea, 28 g of anhydrous sodium acetate and 25 g of acetic acid, refluxing for 8 hours, cooling to 10 ℃, filtering, adding the solid into 300 g of water, stirring for 30 minutes, filtering, adding 300 ml of methanol into the obtained light yellow solid, refluxing for 1 hour, cooling to 10 ℃, filtering, and drying the obtained white-like solid to obtain 5,8-dimethoxy- [1,2,4] triazolo [1,5-C ] pyrimidine-2-amine 55 g.
The invention adopts a brand new two-step synthesis method, has short steps, avoids using highly toxic chemicals in the synthesis process, and is a safe and controllable synthesis method suitable for amplification.
While the embodiments of the present invention have been described in detail, the present invention is not limited thereto, and various changes can be made without departing from the gist of the present invention within the knowledge of those skilled in the art.
Claims (3)
1. A method for synthesizing 5,8-dimethoxy- [1,2,4] triazolo [1,5-C ] pyrimidin-2-amine is characterized by comprising the following steps:
adding a solvent, alkali and an amination reagent into 2.5-dimethoxy-4-hydroxypyrimidine to prepare 3-amino-2.5-methoxypyrimidine (3H) -4-ketone, and adding a cyclization reagent into 3-amino-2.5-methoxypyrimidine (3H) -4-ketone to prepare 5,8-dimethoxy- [1,2,4] triazolo [1,5-C ] pyrimidin-2-amine.
2. The method for synthesizing 5,8-dimethoxy- [1,2,4] triazolo [1,5-C ] pyrimidin-2-amine according to claim 1, comprising the following steps:
s1, 90-110 g of 2.5-dimethoxy-4-hydroxypyrimidine is added into 1.5-2.5L of anhydrous DMF, 270-290 g of anhydrous cesium carbonate is added, nitrogen protection is carried out, stirring is carried out for 1 hour at room temperature, then 170-190 g of O-2,4,6-trimethylbenzenesulfonylhydroxylamine is added, stirring is carried out for 6 hours at room temperature, then heating is carried out to 50 ℃, stirring is carried out for 5 hours, cooling is carried out to 10 ℃, filtering is carried out, 4-6L of water and 0.5-1.5L of ethyl acetate are added, stirring is carried out for 30 minutes, liquid separation is carried out, the ethyl acetate layer is washed once by 190-210 ml of water, and decompression is carried out to remove the solvent to obtain a light yellow solid, namely 3-amino-2.5-methoxypyrimidine (3H) -4-one;
s2, taking the product 3-amino-2, 5-methoxypyrimidine (3H) -4-ketone in the first step, adding the product into 560 to 650 ml of acetonitrile, adding 20 to 30 g of urea, 27 to 29 g of anhydrous sodium acetate and 24 to 26 g of acetic acid, refluxing for 8 hours, cooling to 10 ℃, filtering, adding the solid into 290 to 310 g of water, stirring for 30 minutes, filtering, adding 290 to 310 ml of methanol into the obtained light yellow solid, refluxing for 1 hour, cooling to 10 ℃, filtering, and drying the obtained white-like solid to obtain 5,8-dimethoxy- [1,2,4] triazolo [1,5-C ] pyrimidin-2-amine.
3. The method of claim 2 for synthesizing 5,8-dimethoxy- [1,2,4] triazolo [1,5-C ] pyrimidin-2-amine, comprising the steps of:
s1, adding 100 g of 2, 5-dimethoxy-4-hydroxypyrimidine into 2L of anhydrous DMF, adding 280 g of anhydrous cesium carbonate, stirring at room temperature for 1 hour under the protection of nitrogen, adding 180 g of O-2,4,6-trimethylbenzenesulfonylhydroxylamine, stirring at room temperature for 6 hours, heating to 50 ℃, stirring for 5 hours, cooling to 10 ℃, filtering, adding 5L of water and 1L of ethyl acetate, stirring for 30 minutes, separating liquid, washing an ethyl acetate layer once by using 200 ml of water, and evaporating the solvent under reduced pressure to obtain a light yellow solid;
s2, taking 60 g of the product 3-amino-2, 5-methoxypyrimidine (3H) -4-ketone in the first step, adding the product into 600 ml of acetonitrile, adding 25 g of urea, 28 g of anhydrous sodium acetate and 25 g of acetic acid, refluxing for 8 hours, cooling to 10 ℃, filtering, adding the solid into 300 g of water, stirring for 30 minutes, filtering, adding 300 ml of methanol into the obtained light yellow solid, refluxing for 1 hour, cooling to 10 ℃, filtering, and drying the obtained white-like solid to obtain 5,8-dimethoxy- [1,2,4] triazolo [1,5-C ] pyrimidin-2-amine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211136529.7A CN115417875A (en) | 2022-09-19 | 2022-09-19 | Synthesis method of 5,8-dimethoxy- [1,2,4] triazolo [1,5-C ] pyrimidine-2-amine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211136529.7A CN115417875A (en) | 2022-09-19 | 2022-09-19 | Synthesis method of 5,8-dimethoxy- [1,2,4] triazolo [1,5-C ] pyrimidine-2-amine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115417875A true CN115417875A (en) | 2022-12-02 |
Family
ID=84205221
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211136529.7A Pending CN115417875A (en) | 2022-09-19 | 2022-09-19 | Synthesis method of 5,8-dimethoxy- [1,2,4] triazolo [1,5-C ] pyrimidine-2-amine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115417875A (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002062301A2 (en) * | 2001-02-07 | 2002-08-15 | Farrington Pharmaceuticals, Llc | Method and composition for rejuvinating cells, tissues, organs, hair and nails |
| US20050009876A1 (en) * | 2000-07-31 | 2005-01-13 | Bhagwat Shripad S. | Indazole compounds, compositions thereof and methods of treatment therewith |
| US20110295003A1 (en) * | 2010-05-25 | 2011-12-01 | Dow Agrosciences Llc | PROCESS FOR THE PREPARATION OF 5-SUBSTITUTED-8-ALKOXY[1,2,4]TRIAZOLO[1,5-c]PYRIMIDIN-2-AMINES |
| CN103232453A (en) * | 2013-04-18 | 2013-08-07 | 黑龙江大学 | Synthesizing method of 2-amino-5,8-dimethoxy[1,2,4]-triazolo[1,5-c]-pyrimidine |
| US20140081023A1 (en) * | 2012-09-14 | 2014-03-20 | Dow Agrosciences Llc | PROCESS FOR THE PREPARATION OF 2-AMINO-5,8-DIMETHOXY[1,2,4]TRIAZOLO[1,5-c]PYRIMIDINE FROM 4-CHLORO-2,5-DIMETHOXYPYRIMIDINE |
| CN113564915A (en) * | 2021-07-29 | 2021-10-29 | 安徽唯诗杨信息科技有限公司 | Ionic antibacterial anti-mite heat storage fabric and processing technology thereof |
-
2022
- 2022-09-19 CN CN202211136529.7A patent/CN115417875A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050009876A1 (en) * | 2000-07-31 | 2005-01-13 | Bhagwat Shripad S. | Indazole compounds, compositions thereof and methods of treatment therewith |
| WO2002062301A2 (en) * | 2001-02-07 | 2002-08-15 | Farrington Pharmaceuticals, Llc | Method and composition for rejuvinating cells, tissues, organs, hair and nails |
| US20110295003A1 (en) * | 2010-05-25 | 2011-12-01 | Dow Agrosciences Llc | PROCESS FOR THE PREPARATION OF 5-SUBSTITUTED-8-ALKOXY[1,2,4]TRIAZOLO[1,5-c]PYRIMIDIN-2-AMINES |
| US20140081023A1 (en) * | 2012-09-14 | 2014-03-20 | Dow Agrosciences Llc | PROCESS FOR THE PREPARATION OF 2-AMINO-5,8-DIMETHOXY[1,2,4]TRIAZOLO[1,5-c]PYRIMIDINE FROM 4-CHLORO-2,5-DIMETHOXYPYRIMIDINE |
| CN103232453A (en) * | 2013-04-18 | 2013-08-07 | 黑龙江大学 | Synthesizing method of 2-amino-5,8-dimethoxy[1,2,4]-triazolo[1,5-c]-pyrimidine |
| CN113564915A (en) * | 2021-07-29 | 2021-10-29 | 安徽唯诗杨信息科技有限公司 | Ionic antibacterial anti-mite heat storage fabric and processing technology thereof |
Non-Patent Citations (5)
| Title |
|---|
| AISHA Y. HASSAN等: "Synthesis of some novel pyrazolopyrimidotriazepine, pyrazolotriazolopyrimidine, and pyrazolopyrimidotetrazine derivatives", J. HETEROCYCLIC CHEM., vol. 57, pages 542 - 549 * |
| D.W. RANGNEKAR等: "Synthesis of 7H-Benzo [de] -s-triazolo [5,1-a] isoquinolin-7-one derivatives and study of their fluorescent properties", DYES AND PIGMENTS, vol. 8, no. 4, pages 291 - 299 * |
| MASAHIRO IMAIZUMI等: "Novel uracil derivatives; newly synthesized centrally acting agents", CHEMICAL & PHARMACEUTICAL BULLETIN, vol. 40, no. 7, pages 1808 - 1813 * |
| P.K. BRIDSON等: "The reaction of 5-aminoimidazole-4-carbohydrazides with orthoesters", J. HETEROCYCLIC CHEM., vol. 22, no. 3, pages 753 - 755 * |
| 张富青 等: "五氟磺草胺中间体2-氨基-5,8-二甲氧基[1,2,4]三唑[1,5-c]嘧啶的合成研究", 现代农药, vol. 12, no. 6, pages 17 - 19 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105152985A (en) | Cyclic process for the production of taurine from monoethanolamine | |
| CN111606827B (en) | Method for preparing chiral amine intermediate of edoxaban | |
| WO2023201802A1 (en) | Synthesis method for ensitrelvir | |
| JP2016531925A (en) | Intermediate production method for pemetrexed production and method for producing high purity pemetrexed using the same | |
| CN104961710A (en) | Synthesis method of dinotefuran | |
| CN115417875A (en) | Synthesis method of 5,8-dimethoxy- [1,2,4] triazolo [1,5-C ] pyrimidine-2-amine | |
| CN109293582B (en) | Preparation method for synthesizing 4-amino-2, 6-dimethoxypyrimidine | |
| CN113336761B (en) | Preparation method of JAK inhibitor key intermediate | |
| CN109438307A (en) | A kind of preparation method of L- selenomethionine | |
| CN105693581B (en) | Method for preparing methylthio diafenthiuron | |
| CN112679440B (en) | Preparation method of 5-n-butyl-2-ethylamino-4-hydroxy-6-methylpyrimidine | |
| CN105175294B (en) | Method for synthesizing sulfanilamide by using chlorobenzene as raw material | |
| CN111004184A (en) | Synthesis process of 4, 6-dichloropyrimidine | |
| CN106748884B (en) | Preparation method of bicalutamide intermediate | |
| EP0030475B1 (en) | Process for producing solutions of aziridine-2-carboxylic acid salts | |
| CN110938036A (en) | Preparation method of 4-iodine-1H-imidazole | |
| CN110776413A (en) | Preparation method and application of manganese abietate | |
| US2809966A (en) | Aminobenzene-sulphoiyyl-z-amino- | |
| US3251875A (en) | N-nitroso derivatives | |
| US4393000A (en) | Cyclization process for producing aziridine-2-carboxylic acid or its salts | |
| CN117247339B (en) | Preparation method of alkylamine derivative | |
| CN110668951B (en) | Synthesis process of selegiline hydrochloride | |
| CN112239395B (en) | Method for synthesizing 6-chloro-1-hexanol by using 1,6-hexanediol and cyanuric chloride as raw materials | |
| CN107739343A (en) | A kind of environment-friendly type technique for producing Quizalotop-ethyl | |
| CN115850107A (en) | Industrial synthesis method of tiramide hydrochloride |
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 |