CN115403534B - Preparation method of 3- (chloromethyl) -1-methyl-1H-1, 2,4 triazole hydrochloride - Google Patents
Preparation method of 3- (chloromethyl) -1-methyl-1H-1, 2,4 triazole hydrochloride Download PDFInfo
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- CN115403534B CN115403534B CN202210958419.2A CN202210958419A CN115403534B CN 115403534 B CN115403534 B CN 115403534B CN 202210958419 A CN202210958419 A CN 202210958419A CN 115403534 B CN115403534 B CN 115403534B
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- KISIDCUHOLGEPR-UHFFFAOYSA-N 3-(chloromethyl)-1-methyl-1,2,4-triazole;hydrochloride Chemical compound Cl.CN1C=NC(CCl)=N1 KISIDCUHOLGEPR-UHFFFAOYSA-N 0.000 title claims abstract description 18
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- 238000007363 ring formation reaction Methods 0.000 claims abstract description 18
- 238000006243 chemical reaction Methods 0.000 claims abstract description 17
- 238000007254 oxidation reaction Methods 0.000 claims abstract description 15
- TXNSZCSYBXHETP-UHFFFAOYSA-N 2-chloro-n-(hydroxymethyl)acetamide Chemical compound OCNC(=O)CCl TXNSZCSYBXHETP-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000002994 raw material Substances 0.000 claims abstract description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 22
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 8
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical group O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 claims description 8
- 239000003054 catalyst Substances 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 239000007800 oxidant agent Substances 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 5
- SOBVGTVPRQSQHU-UHFFFAOYSA-N 2-chloro-n-formylacetamide Chemical compound ClCC(=O)NC=O SOBVGTVPRQSQHU-UHFFFAOYSA-N 0.000 claims description 4
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 230000001590 oxidative effect Effects 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 3
- KJDJPXUIZYHXEZ-UHFFFAOYSA-N hydrogen sulfate;methylaminoazanium Chemical compound CN[NH3+].OS([O-])(=O)=O KJDJPXUIZYHXEZ-UHFFFAOYSA-N 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 239000000706 filtrate Substances 0.000 claims description 2
- 239000012074 organic phase Substances 0.000 claims description 2
- 239000002244 precipitate Substances 0.000 claims description 2
- 230000001105 regulatory effect Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- FADDLIDROGVHOT-UHFFFAOYSA-N 3-chloro-2-oxopropanamide Chemical compound NC(=O)C(=O)CCl FADDLIDROGVHOT-UHFFFAOYSA-N 0.000 claims 1
- 238000006555 catalytic reaction Methods 0.000 claims 1
- 150000003222 pyridines Chemical class 0.000 claims 1
- 239000012429 reaction media Substances 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1
- 238000011031 large-scale manufacturing process Methods 0.000 abstract description 2
- 238000001308 synthesis method Methods 0.000 description 8
- 239000000047 product Substances 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 2
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
- CYTYCFOTNPOANT-UHFFFAOYSA-N Perchloroethylene Chemical group ClC(Cl)=C(Cl)Cl CYTYCFOTNPOANT-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000010907 mechanical stirring Methods 0.000 description 2
- 239000012450 pharmaceutical intermediate Substances 0.000 description 2
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 2
- 238000006798 ring closing metathesis reaction Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 229950011008 tetrachloroethylene Drugs 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 description 1
- 239000005751 Copper oxide Substances 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000005708 Sodium hypochlorite Substances 0.000 description 1
- OFLXLNCGODUUOT-UHFFFAOYSA-N acetohydrazide Chemical compound C\C(O)=N\N OFLXLNCGODUUOT-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229910000431 copper oxide Inorganic materials 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- DZGCGKFAPXFTNM-UHFFFAOYSA-N ethanol;hydron;chloride Chemical compound Cl.CCO DZGCGKFAPXFTNM-UHFFFAOYSA-N 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 150000005826 halohydrocarbons Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
Abstract
The invention discloses a preparation method of 3- (chloromethyl) -1-methyl-1H-1, 2,4 triazole hydrochloride, which takes 2-chloro-N- (hydroxymethyl) acetamide as a reaction raw material, and prepares the 3- (chloromethyl) -1-methyl-1H-1, 2,4 triazole hydrochloride through oxidation reaction and ring closure reaction in sequence, wherein the reaction route is as follows:
Description
Technical Field
The invention belongs to the technical field of synthesis of pharmaceutical intermediates, and particularly relates to a preparation method of an anti-neocrown drug intermediate 3- (chloromethyl) -1-methyl-1H-1, 2,4 triazole hydrochloride.
Background
3- (chloromethyl) -1-methyl-1H-1, 2, 4-triazole hydrochloride is a pharmaceutical intermediate, whose accession number CAS is: 135206-76-7, are currently used in new crown drugs in salt field. In the prior art, the preparation of 3- (chloromethyl) -1-methyl-1H-1, 2, 4-triazole hydrochloride is generally carried out in the following manner:
mode one:
the mode is synthesized by adopting a four-step one-pot method such as hydrogen drawing, ring closing, salification and the like by using N-methylformylhydrazine, and is the currently mainstream synthesis method. The synthesis method has the problems that the starting materials are difficult to obtain and the ring closure yield is low.
Mode two:
the route is reported in the literature, and obviously, the method has very low atom utilization rate, chlorination, serious environmental pollution, long steps and low yield.
Disclosure of Invention
Aiming at the problems in the prior art, the invention aims to provide a preparation method of 3- (chloromethyl) -1-methyl-1H-1, 2,4 triazole hydrochloride, which solves the technical problems of difficult raw material acquisition and high cost in the existing preparation process of the compound.
The invention takes commercially produced N-methylol chloroacetamide as a reaction raw material, and the preparation of the compound is completed through oxidation, ring closure and salification reactions, and the synthetic route is as follows:
1) Oxidation reaction: taking N-methylol chloroacetamide with the formula amount, and performing oxidation reaction in a reaction solvent to convert the N-methylol chloroacetamide into a compound shown in a formula (I);
2) Ring closure reaction: the compound shown in the formula (I) is subjected to ring closure reaction in the presence of methyl hydrazine, and then hydrochloric acid is used for salifying to prepare 3- (chloromethyl) -1-methyl-1H-1, 2, 4-triazole hydrochloride shown in the formula (II);
wherein, the structural formula of the compound I is as follows: chloroacetyl formamide
The structural formula of the compound II is as follows:
further, in step 1), the reaction is performed in MnO 2 For example, the amount of oxidizing agent for the oxidation reaction is 1 to 6 molar equivalents of the starting material, preferably 4 molar equivalents.
Further, in the step 1), the organic solvent for the oxidation reaction is any one of halogenated hydrocarbon, tetrachloroethylene, toluene, NMP, DMSO, and diethylene glycol dimethyl ether, and the subsequent examples are exemplified by chloroform.
Further, in the step 1), the temperature of the oxidation reaction is 10-60 ℃ and the reaction time is 2-48h.
Further, in the step 1), the oxidizing agent is one of manganese dioxide, sodium hypochlorite and peracetic acid.
In the step 2), the organic solvent for the ring closure reaction is any one of halohydrocarbon, tetrahydrofuran, tetrachloroethylene, dioxane, cyclohexane, toluene, NMP, DMSO and diethylene glycol dimethyl ether.
Further, in the step 2), the catalyst for the ring closure reaction is any one or more of p-toluenesulfonic acid, trifluoroacetic acid, benzenesulfonic acid, sulfuric acid, phosphoric acid and their pyridinium salts.
Further, in the step 2), the temperature of the ring closure reaction is 50-80 ℃ and the reaction time is 5-8h.
Further, in step 2), the pH of the ring closure reaction is 6-7.
The preparation method is simple, mild in reaction condition, easy to operate and realize, easy to obtain the needed raw materials, low in cost and suitable for large-scale production.
Detailed Description
The following description of the technical solution of the present invention will be made clearly and completely in connection with specific embodiments, so as to better understand the technical solution.
Example 1
The preparation of 3- (chloromethyl) -1-methyl-1H-1, 2, 4-triazole hydrochloride comprises two steps of reaction: the first step is oxidation reaction, and the second step is ring closing reaction.
1) Oxidation reaction: 124g (1.00 mol) of 2-chloro-N- (hydroxymethyl) acetamide, 350g (4 mol) of manganese dioxide, 200mL of chloroform were placed in a 1L three-necked flask equipped with a thermometer, a condenser and mechanical stirring, and the temperature was slowly raised to 60℃for reaction under the protection of nitrogen. TLC monitors the reaction progress, after 12 hours, the reaction is finished, the temperature is reduced to room temperature, the filtration is carried out (a layer of diatomite is added in a suction filtration funnel), the filter cake is leached by chloroform, the filtrate is taken and distilled in a rotary way, 22.95g of beige solid which is the crude product of the compound of the formula I is obtained, the yield is 70%, 1 HNMR (500 MHz, CDCl 3 ) δ 9.15 (d, J = 9.4 Hz, 1H), 9.07 (s, 1H), 4.18 (s, 2H)；
2) Ring closure reaction: 200mL of chloroform, 36g (0.3 mol,1.0 eq) of chloroacetyl formamide and 57g (0.4 mol,1.5 eq) of methylhydrazine sulfate are added into a 500mL three-necked flask equipped with a thermometer and a condenser and mechanically stirred, after stirring uniformly, 0.070g (0.41 eq) of p-toluenesulfonic acid is added, then the temperature is slowly heated to 50 ℃, the reaction end point is about 4 hours, 50mL of 2mol/L hydrochloric acid is added dropwise after cooling to room temperature, stirring is carried out at room temperature for 2 hours, then the pH value is regulated to 6-7 by saturated sodium carbonate solution, the aqueous layer is extracted by chloroform (100 mL multiplied by 2), the organic phases are combined, anhydrous sodium sulfate and active carbon are added, stirring is carried out for 6 hours, a hydrochloric acid ethanol solution is added dropwise under the ice water bath condition, white precipitate is obtained, and the finished product is obtained after filtration and drying is obtained. The yield thereof was found to be 65%.1HNMR (500 MHz, CDCl 3) delta 3.97 (s, 3H), 8.08 (s, 2H), 7.83 (s, 1H)
Example 2
The synthesis method was the same as that of example 1, except that 250g of 2-chloro-N- (hydroxymethyl) acetamide, 700g of manganese dioxide and 1L of chloroform were added to a 1L three-necked flask equipped with a thermometer, a condenser and mechanical stirring under nitrogen protection, and stirred at room temperature for 48 hours, and the obtained product was worked up according to the method of example 1, whereby the yield was 83%.
Example 3
The synthesis method is the same as the first oxidation reaction in example 1, except that the solvent is changed into dichloromethane, the reaction is carried out at room temperature, and the product yield after post-treatment is 86%.
Example 4
The synthesis method is the same as that of example 1 except that the solvent of the second ring closure reaction is modified by chloroform to prepare diethylene glycol dimethyl ether, and the product yield is 60.2%.
Example 5
The synthesis was the same as in example 1 except that a small amount of copper oxide was added to the oxidant of the first oxidation reaction, and the yield of the oxidation reaction product was 74.2%.
Example 6
The synthesis was the same as in example 1 except that the catalyst for the ring closure reaction, p-toluenesulfonic acid, was increased from 0.05e to 0.1e, and the yield of the ring closure reaction was 58.7%.
Example 7
The synthesis method was the same as in example 1 except that the catalyst for the ring closure reaction was changed from p-toluenesulfonic acid to trifluoroacetic acid, and the product yield was 62.4%.
Example 8
The synthesis method is the same as in example 1, except that the catalyst of the ring closure reaction is changed from p-toluenesulfonic acid to pyridine hydrochloride, and the product yield is 66.2%.
Example 9
The synthesis method was the same as in example 1 except that the temperature of the ring closure reaction was changed from 50℃to 62℃under reflux, and the product yield was 56.2%.
Claims (5)
1. The preparation method of the 3- (chloromethyl) -1-methyl-1H-1, 2,4 triazole hydrochloride is characterized in that the preparation method takes 2-chloro-N- (hydroxymethyl) acetamide as a reaction raw material, and the 3- (chloromethyl) -1-methyl-1H-1, 2,4 triazole hydrochloride is prepared by oxidation reaction and ring closure reaction in sequence, and the specific steps are as follows:
1) Oxidation reaction: under the protection of nitrogen, taking 2-chloro-N- (hydroxymethyl) acetamide and oxidant with formula amount, taking chloroform as reaction medium, and adding MnO 2 The compound chloracetyl formamide shown in the formula (I) is prepared by the reaction under the catalysis of the catalyst, wherein the structural formula of the formula (I) is as follows:
（Ⅰ）；
the oxidant is manganese dioxide, and the amount of the oxidant is 4-6 molar equivalents of the raw material;
2) Ring closure reaction: the method comprises the steps of taking compound chloroacetyl formamide shown in a formula (I) and methyl hydrazine sulfuric acid as raw materials, stirring and reacting under the action of a catalyst in an organic solvent as a medium, adding hydrochloric acid when the reaction is finished, continuously stirring at room temperature, regulating the pH value of saturated sodium carbonate solution after the reaction is finished, adding chloroform for layering, extracting a water layer by using chloroform, combining organic phases, drying by using anhydrous sodium sulfate, filtering, concentrating filtrate under reduced pressure to obtain white precipitate, namely 3- (chloromethyl) -1-methyl-1H-1, 2,4 triazole hydrochloride shown in a formula (II), wherein the structural formula of the formula (II) is as follows:
（Ⅱ）；
the catalyst is any one or more of p-toluenesulfonic acid, trifluoroacetic acid and pyridine salts thereof; the organic solvent is any one of chloroform and diethylene glycol dimethyl ether.
2. The process for preparing 3- (chloromethyl) -1-methyl-1H-1, 2, 4-triazole hydrochloride according to claim 1, wherein the temperature of the oxidation reaction in step 1) is 10 to 60℃and the reaction time is 2 to 48 hours.
3. The process for the preparation of 3- (chloromethyl) -1-methyl-1H-1, 2,4 triazole hydrochloride according to claim 1, wherein in step 2) the molar equivalent ratio of chloroacetylcarboxamide to methylhydrazine sulfuric acid is 1:1-4.
4. The process for preparing 3- (chloromethyl) -1-methyl-1H-1, 2, 4-triazole hydrochloride according to claim 1, wherein in step 2), the temperature of the ring-closure reaction is 50 to 90℃and the reaction time is 2 to 8 hours.
5. The process for the preparation of 3- (chloromethyl) -1-methyl-1H-1, 2, 4-triazole hydrochloride according to claim 1, wherein in step 2), the pH is from 6 to 7.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6413997B1 (en) * | 1998-10-23 | 2002-07-02 | Dow Agrosciences Llc | 3-(substituted phenyl)-5-(substituted heterocyclyl)-1,2,4-triazole compounds |
| CN107879992A (en) * | 2017-12-23 | 2018-04-06 | 上海晋鲁医药科技有限公司 | A kind of preparation method of (base of 1 methyl 1H [1,2,4] triazole 3) methanol |
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- 2022-08-11 CN CN202210958419.2A patent/CN115403534B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6413997B1 (en) * | 1998-10-23 | 2002-07-02 | Dow Agrosciences Llc | 3-(substituted phenyl)-5-(substituted heterocyclyl)-1,2,4-triazole compounds |
| CN107879992A (en) * | 2017-12-23 | 2018-04-06 | 上海晋鲁医药科技有限公司 | A kind of preparation method of (base of 1 methyl 1H [1,2,4] triazole 3) methanol |
Non-Patent Citations (1)
| Title |
|---|
| Jongbok Lee 等.Synthesis of 1,3,5-trisubstituted-1,2,4-triazoles by microwave-assisted N-acylation of amide derivatives and the consecutive reaction with hydrazine hydrochlorides.《Tetrahedron》.2012,第68卷第2045-2051页. * |
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