CN116496230A - Preparation method of 2, 3-dihydro-4H-1, 3-benzothiazine-4-ketone - Google Patents
Preparation method of 2, 3-dihydro-4H-1, 3-benzothiazine-4-ketone Download PDFInfo
- Publication number
- CN116496230A CN116496230A CN202310479244.1A CN202310479244A CN116496230A CN 116496230 A CN116496230 A CN 116496230A CN 202310479244 A CN202310479244 A CN 202310479244A CN 116496230 A CN116496230 A CN 116496230A
- Authority
- CN
- China
- Prior art keywords
- dihydro
- reaction
- benzisothiazolin
- benzothiazin
- producing
- 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
- 238000002360 preparation method Methods 0.000 title claims abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims abstract description 34
- DMSMPAJRVJJAGA-UHFFFAOYSA-N benzo[d]isothiazol-3-one Chemical compound C1=CC=C2C(=O)NSC2=C1 DMSMPAJRVJJAGA-UHFFFAOYSA-N 0.000 claims abstract description 25
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims abstract description 23
- PLGGWNRXUVCKEK-UHFFFAOYSA-N 2,3-dihydro-1,3-benzothiazin-4-one Chemical compound C1=CC=C2C(=O)NCSC2=C1 PLGGWNRXUVCKEK-UHFFFAOYSA-N 0.000 claims abstract description 19
- 239000012363 selectfluor Substances 0.000 claims abstract description 16
- XZXYQEHISUMZAT-UHFFFAOYSA-N 2-[(2-hydroxy-5-methylphenyl)methyl]-4-methylphenol Chemical compound CC1=CC=C(O)C(CC=2C(=CC=C(C)C=2)O)=C1 XZXYQEHISUMZAT-UHFFFAOYSA-N 0.000 claims abstract description 9
- 229940107816 ammonium iodide Drugs 0.000 claims abstract description 9
- 239000007810 chemical reaction solvent Substances 0.000 claims abstract description 9
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims abstract description 9
- 229940071870 hydroiodic acid Drugs 0.000 claims abstract description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 7
- 238000004440 column chromatography Methods 0.000 claims description 6
- 230000035484 reaction time Effects 0.000 claims description 6
- 239000012295 chemical reaction liquid Substances 0.000 claims description 5
- 238000000746 purification Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 9
- 239000002994 raw material Substances 0.000 abstract description 5
- 239000000654 additive Substances 0.000 abstract description 3
- 238000003889 chemical engineering Methods 0.000 abstract description 2
- 239000012847 fine chemical Substances 0.000 abstract description 2
- 125000000623 heterocyclic group Chemical group 0.000 abstract description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 abstract description 2
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 9
- 239000002904 solvent Substances 0.000 description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 229930040373 Paraformaldehyde Natural products 0.000 description 3
- 229920002866 paraformaldehyde Polymers 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- GBEMNSRGSOIQIX-UHFFFAOYSA-N 1,3-benzothiazin-4-one Chemical class C1=CC=C2C(=O)N=CSC2=C1 GBEMNSRGSOIQIX-UHFFFAOYSA-N 0.000 description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 1
- PFRUBEOIWWEFOL-UHFFFAOYSA-N [N].[S] Chemical class [N].[S] PFRUBEOIWWEFOL-UHFFFAOYSA-N 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000013475 authorization Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000012025 fluorinating agent Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D279/04—1,3-Thiazines; Hydrogenated 1,3-thiazines
- C07D279/08—1,3-Thiazines; Hydrogenated 1,3-thiazines condensed with carbocyclic rings or ring systems
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the field of fine chemical engineering, and relates to a preparation method of 2, 3-dihydro-4H-1, 3-benzothiazine-4-ketone. Comprising the following steps: adding 1, 2-benzisothiazolin-3-one, selectfluor, ammonium iodide and hydroiodic acid into a sealed tube containing a reaction solvent acetonitrile or 1,4-Dioxane for reaction, and purifying after the reaction is finished to obtain 2, 3-dihydro-4H-1, 3-benzothiazine-4-one. The invention uses cheap and easily available 1, 2-benzisothiazolin-3-one and Selectfluor as raw materials, and ammonium iodide and hydroiodic acid as additives to construct the 2, 3-dihydro-4H-1, 3-benzothiazin-4-one. Wherein SelectFluor can provide a methylene source, and is inserted into a five-membered heterocycle of 1, 2-benzisothiazolin-3-one serving as a raw material to construct 2, 3-dihydro-4H-1, 3-benzothiazin-4-one in one step.
Description
Technical Field
The invention belongs to the field of fine chemical engineering, and relates to a preparation method of 2, 3-dihydro-4H-1, 3-benzothiazine-4-ketone.
Background
2, 3-dihydro-4H-1, 3-benzothiazin-4-one is an important class of sulfur-nitrogen-containing six-membered heterocyclic compounds, which are widely found in various types of natural products, drugs, foods and materials having pharmaceutical activity.
The literature reports that there are only one example of a method for synthesizing 2, 3-dihydro-4H-1, 3-benzothiazin-4-one: 2-methyl ester thiophenol and paraformaldehyde are used as raw materials, ammonium acetate is used as an additive, and the mixture is refluxed in toluene for 15 hours to obtain 2, 3-dihydro-4H-1, 3-benzothiazine-4-ketone with 50 percent yield, and the reaction has the following defects: (1) Using toxic reagent 2-methyl ester thiophenol and paraformaldehyde; (2) the yield is relatively low. Specific synthetic methods are described in (chem. Commun.,2011,47,2137) for support materials.
In previous work, we found that the synthesis of a variety of different 1, 3-benzothiazin-4-one derivatives could be achieved using the fluorinating agent Selectfluor, but this strategy has some limitations: the 1, 3-benzothiazin-4-one derivative with the substituent on N being alkyl can only be synthesized, and when the substituent on N is H or aryl, the reaction can not be carried out (Chinese patent authorization number: ZL201811245251.0; ZL202111461347.2; ZL 202111461346.8).
Disclosure of Invention
The invention aims to provide a novel preparation method of 2, 3-dihydro-4H-1, 3-benzothiazine-4-ketone, which avoids using toxic reagents of 2-methyl ester thiophenol and paraformaldehyde.
The invention relates to a preparation method of 2, 3-dihydro-4H-1, 3-benzothiazine-4-ketone, which comprises the following steps: adding 1, 2-benzisothiazolin-3-one, selectfluor, ammonium iodide and hydroiodic acid into a sealed tube containing a reaction solvent acetonitrile or 1,4-Dioxane for reaction, and purifying after the reaction is finished to obtain 2, 3-dihydro-4H-1, 3-benzothiazine-4-one.
Further, the purification method comprises concentrating the reaction solution and separating by column chromatography.
In order to ensure the efficiency of obtaining the target, the concentration of 1, 2-benzisothiazolin-3-one in the reaction system of the present invention is 0.075 to 0.3mol/L, preferably 0.1mol/L.
To increase the yield, further, NH 4 The molar ratio of the I to the 1, 2-benzisothiazolin-3-one is 1-5:1.
To increase the yield, the molar ratio of HI to 1, 2-benzisothiazolin-3-one is further 1-5:1.
In order to improve the construction efficiency and yield of 2, 3-dihydro-4H-1, 3-benzothiazin-4-one, it is preferable that the reaction solvent is MeCN, and the molar ratio of 1, 2-benzisothiazolin-3-one, selectFluor, ammonium iodide and hydroiodic acid is 1:1:3-5:3-5.
More preferably, the reaction solvent is MeCN,1, 2-benzisothiazolin-3-one, selectfluor, ammonium iodide and hydroiodic acid in a molar ratio of 1.0:1.0:4.0:4.0.
in order to ensure the efficiency of obtaining the target, the reaction temperature is 130-150 ℃, preferably 140 ℃.
In order to ensure the efficiency of the target, the reaction time described in the present invention is 8 to 16 hours, preferably 12 hours.
Compared with the prior art, the invention uses cheap and easily available 1, 2-benzisothiazolin-3-one and Selectfluor as raw materials, and ammonium iodide and hydroiodic acid as additives to construct the 2, 3-dihydro-4H-1, 3-benzothiazine-4-one. Wherein SelectFluor can provide a methylene source, and is inserted into a five-membered heterocycle of 1, 2-benzisothiazolin-3-one serving as a raw material to construct 2, 3-dihydro-4H-1, 3-benzothiazin-4-one in one step.
Detailed Description
The invention is further described in detail below in connection with the examples:
example 1
The synthesis method of the 2, 3-dihydro-4H-1, 3-benzothiazine-4-ketone comprises the following steps: acetonitrile (3 mL), 1, 2-benzisothiazolin-3-one (0.3 mmol), selectFluor (0.3 mmol), NH were added sequentially to a 25mL vial 4 I (1.2 mmol) and HI (1.2 mmol), the reaction temperature was controlled at 140℃and the reaction was vigorously stirred for 12 hours. And after the reaction is finished, concentrating the reaction liquid and separating by column chromatography to obtain the 2, 3-dihydro-4H-1, 3-benzothiazine-4-ketone with the separation yield of 80 percent.
Nuclear magnetic data and mass spectrum data of target products:
1 H NMR(300MHz,CDCl 3 )δ8.81(br,1H),7.98(d,J＝7.6Hz,1H),7.29–7.13(m,3H),4.46(d,J＝3.0Hz,2H). 13 C NMR(75MHz,CDCl 3 )δ165.42,136.80,131.06,128.96,127.58,126.38,125.00,41.45.MS(EI)＝165.0[M] + .
example 2 (NH) 4 Dosage screening of I
With reference to example 1, only NH was adjusted 4 The dosage of I is as follows: acetonitrile (3 mL), 1, 2-benzisothiazolin-3-one (0.3 mmol), selectFluor (0.3 mmol), NH were added sequentially to a 25mL vial 4 I and HI (1.2 mmol), the reaction temperature was controlled at 140℃and the reaction was stirred vigorously for 12 hours. After the reaction is finished, the reaction liquid is concentrated and separated by column chromatography in sequence, and the specific conditions are as follows:
(1)NH 4 the dosage of I is 0, and the yield of the target product is 29%;
(2)NH 4 the dosage of I is 0.3mmol, and the yield of the target product is 36%;
(3)NH 4 the dosage of I is 0.6mmol, and the yield of the target product is 50%;
(4)NH 4 the dosage of I is 0.9mmol, and the yield of the target product is 65%;
(5)NH 4 the dosage of I is 1.2mmol, and the yield of the target product is 80%;
(6)NH 4 the amount of I used was 1.5mmol, and the yield of the target product was 77%.
Example 3 (quantity screening of HI)
With reference to the method of example 1, only the amount of HI was adjusted, specifically: acetonitrile (2 mL), 1, 2-benzisothiazolin-3-one (0.3 mmol), selectFluor (0.3 mmol), NH were added sequentially to a 25mL vial 4 I (1.2 mmol) and HI, the reaction temperature was controlled at 140℃and the reaction was stirred vigorously for 12 hours. After the reaction is finished, the reaction liquid is concentrated and separated by column chromatography in sequence, and the specific conditions are as follows:
(1) The HI dosage is 0, and the yield of the target product is 0%;
(2) The HI dose is 0.3mmol, and the yield of the target product is 30%;
(3) HI was used in an amount of 0.6mmol and the yield of the target product was 43%;
(4) The HI dose was 0.9mmol and the yield of the target product was 60%;
(5) The HI dose is 1.2mmol, and the yield of the target product is 80%;
(6) HI was used in an amount of 1.5mmol and the yield of the desired product was 70%.
Example 4 (screening of different reaction solvents)
With reference to the method of example 1, only the kind of the solvent is adjusted, and the specific method is as follows: into a 25 mL-sealed tube, various reaction solvents (3 mL), 1, 2-benzisothiazolin-3-one (0.3 mmol), selectFluor (0.3 mmol) and NH were added in this order 4 I (1.2 mmol) and HI (1.2 mmol), the reaction temperature was controlled at 140℃and the reaction was vigorously stirred for 12 hours. After the reaction is finished, the reaction liquid is concentrated and separated by column chromatography in sequence, and the specific conditions are as follows:
(1) The yield of the target product was 80% using MeCN as solvent;
(2) The yield of the target product was 48% using THF as solvent;
(3) The yield of the target product was 19% using DCM as solvent;
(4) The yield of the solvent target product was 54% using 1, 4-Dioxane;
(5) The yield of the solvent target product was 21% using DCE.
(6) In addition, the target product cannot be isolated by using DMF, DMSO, toluene, methanol, and acetone as solvents.
Further, on the basis of the above-mentioned example 1, the concentration of 1, 2-benzisothiazolin-3-one in the reaction system was controlled to be 0.075 to 0.3mol/L; and/or the reaction temperature is 130-150 ℃; and/or when the reaction time is 8-16h, the yield is over 50 percent, and the reaction efficiency is higher. When the concentration of the 1, 2-benzisothiazolin-3-one in the reaction system is 0.075-0.15mol/L; and/or the reaction temperature is 130-150 ℃; and/or when the reaction time is 10-16h, the yield is more than 60%, and when the concentration of the 1, 2-benzisothiazolin-3-one in the reaction system is 0.075-0.1mol/L; and/or the reaction temperature is 140-150 ℃; and/or when the reaction time is 10-14h, the yield is over 70 percent.
The foregoing describes alternative embodiments of the present invention to teach those skilled in the art how to implement and reproduce the invention. Some conventional technical aspects have been simplified and omitted in order to teach the inventive solution. Those skilled in the art will appreciate variations from this aspect that fall within the scope of the invention.
Claims (10)
1. A preparation method of 2, 3-dihydro-4H-1, 3-benzothiazine-4-ketone is characterized in that: the method comprises the following steps: adding 1, 2-benzisothiazolin-3-one, selectfluor, ammonium iodide and hydroiodic acid into a sealed tube containing a reaction solvent acetonitrile or 1,4-Dioxane for reaction, and purifying after the reaction is finished to obtain 2, 3-dihydro-4H-1, 3-benzothiazine-4-one.
2. The method for producing 2, 3-dihydro-4H-1, 3-benzothiazin-4-one according to claim 1, wherein: the purification method comprises the steps of concentrating and separating the reaction liquid by column chromatography in sequence.
3. The method for producing 2, 3-dihydro-4H-1, 3-benzothiazin-4-one according to claim 1, wherein: the concentration of the 1, 2-benzisothiazolin-3-one in the reaction system is 0.075-0.3mol/L; and/or the reaction temperature is 130-150 ℃; and/or the reaction time is 8-16h.
4. The method for producing 2, 3-dihydro-4H-1, 3-benzothiazin-4-one according to claim 1, wherein: the concentration of 1, 2-benzisothiazolin-3-one in the reaction system was 0.1mol/L.
5. The method for producing 2, 3-dihydro-4H-1, 3-benzothiazin-4-one according to claim 1, wherein: NH (NH) 4 The molar ratio of the I to the 1, 2-benzisothiazolin-3-one is 1-5:1.
6. The method for producing 2, 3-dihydro-4H-1, 3-benzothiazin-4-one according to claim 1, wherein: the molar ratio of HI to 1, 2-benzisothiazolin-3-one is 1-5:1.
7. The method for producing 2, 3-dihydro-4H-1, 3-benzothiazin-4-one according to claim 1, wherein: the reaction solvent is MeCN, and the mole ratio of 1, 2-benzisothiazolin-3-one, selectfluor, ammonium iodide and hydroiodic acid is 1:1:3-5:3-5.
8. The method for producing 2, 3-dihydro-4H-1, 3-benzothiazin-4-one according to claim 1, wherein: the reaction solvent is MeCN, and the molar ratio of the 1, 2-benzisothiazolin-3-one, the Selectfluor, the ammonium iodide and the hydroiodic acid is 1.0:1.0:4.0:4.0.
9. the method for producing 2, 3-dihydro-4H-1, 3-benzothiazin-4-one according to claim 1, wherein: the reaction temperature was 140 degrees celsius.
10. The method for producing 2, 3-dihydro-4H-1, 3-benzothiazin-4-one according to claim 1, wherein: the reaction time was 12 hours.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310479244.1A CN116496230A (en) | 2023-04-28 | 2023-04-28 | Preparation method of 2, 3-dihydro-4H-1, 3-benzothiazine-4-ketone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310479244.1A CN116496230A (en) | 2023-04-28 | 2023-04-28 | Preparation method of 2, 3-dihydro-4H-1, 3-benzothiazine-4-ketone |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116496230A true CN116496230A (en) | 2023-07-28 |
Family
ID=87328083
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310479244.1A Pending CN116496230A (en) | 2023-04-28 | 2023-04-28 | Preparation method of 2, 3-dihydro-4H-1, 3-benzothiazine-4-ketone |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116496230A (en) |
-
2023
- 2023-04-28 CN CN202310479244.1A patent/CN116496230A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN113105468B (en) | Polycyclic spiroindolone compound containing benzopyrone and preparation method and application thereof | |
| CN111646964B (en) | Novel method for synthesizing 2H-pyran-2-one derivative by base catalysis | |
| CN112920173A (en) | Chiral chroman compound and synthesis method thereof | |
| CN112778303A (en) | Preparation method of CDK4/6 kinase inhibitor SHR6390 | |
| CN116496230A (en) | Preparation method of 2, 3-dihydro-4H-1, 3-benzothiazine-4-ketone | |
| CN111995554A (en) | Method for preparing asymmetric organic selenium ether compound by metal-free chemical oxidation method | |
| CN115260050B (en) | Method for preparing 3-bromo-N-aryl propionamide by using NBS | |
| CN114853648B (en) | Method for preparing asymmetric disulfide by NBS (N-bromosuccinimide) to promote breakage of thioether C-S bond | |
| CN110551144A (en) | Preparation method of amoxicillin | |
| CN115160220A (en) | Synthesis process of pyridine-N-oxide | |
| CN110804012B (en) | Method for reducing mercaptal or thioketone for desulfurization | |
| CN110172076B (en) | Quinoline derivative containing exocyclic double bond and preparation method thereof | |
| CN108947995B (en) | Preparation method of polysubstituted oxadiazine derivative | |
| CN108047179B (en) | Fullerene dihydrofuran compound and preparation method thereof | |
| CN116496231A (en) | Preparation method of N-phenyl-2, 3-dihydro-4H-1, 3-benzothiazine-4-ketone | |
| CN114478516B (en) | 3, 4-dihydro-2H-quinolizin-2-one compound and preparation method thereof | |
| CN115304557B (en) | Enamine derivative and preparation method thereof | |
| CN112824387B (en) | 2-methyl nicotinate and preparation method and application thereof | |
| CN114181168B (en) | Method for preparing N- (substituent) -2-substituent benzothiazine-4-ketone | |
| CN113999152B (en) | Synthesis method of cis-1-benzyl-2, 4-dialkoxycarbonyl azetidine | |
| CN114507180B (en) | Methyl-substituted azaheterocyclic compound C (sp 3 ) Method for self dehydroalkenylation of H bonds | |
| CN113135865B (en) | Method for preparing N-phenyl-3- (benzotriazole-1-yl) propionamide | |
| CN114181169B (en) | Method for preparing N- (substituent) benzothiazine-4-ketone without participation of metal | |
| CN111333651B (en) | SCF-containing3Or SeCF3Heterocyclic compounds of (5) and process for preparing the same | |
| CN108264531B (en) | Preparation method of anecortave acetate |
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 |