CN115677561B - 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone and synthesis method thereof - Google Patents
1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone and synthesis method thereof Download PDFInfo
- Publication number
- CN115677561B CN115677561B CN202211355015.0A CN202211355015A CN115677561B CN 115677561 B CN115677561 B CN 115677561B CN 202211355015 A CN202211355015 A CN 202211355015A CN 115677561 B CN115677561 B CN 115677561B
- Authority
- CN
- China
- Prior art keywords
- methyl
- tetrahydro
- carbazolone
- reaction
- methylaniline
- 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.)
- Active
Links
- 238000001308 synthesis method Methods 0.000 title claims abstract description 9
- 238000006243 chemical reaction Methods 0.000 claims abstract description 44
- FWFSEYBSWVRWGL-UHFFFAOYSA-N cyclohex-2-enone Chemical compound O=C1CCCC=C1 FWFSEYBSWVRWGL-UHFFFAOYSA-N 0.000 claims abstract description 18
- 238000003756 stirring Methods 0.000 claims abstract description 14
- 238000010438 heat treatment Methods 0.000 claims abstract description 13
- 239000003054 catalyst Substances 0.000 claims abstract description 11
- SFLXUZPXEWWQNH-UHFFFAOYSA-K tetrabutylazanium;tribromide Chemical compound [Br-].[Br-].[Br-].CCCC[N+](CCCC)(CCCC)CCCC.CCCC[N+](CCCC)(CCCC)CCCC.CCCC[N+](CCCC)(CCCC)CCCC SFLXUZPXEWWQNH-UHFFFAOYSA-K 0.000 claims abstract description 10
- 238000000034 method Methods 0.000 claims abstract description 9
- 238000001816 cooling Methods 0.000 claims abstract description 7
- 239000000706 filtrate Substances 0.000 claims abstract description 7
- 238000001914 filtration Methods 0.000 claims abstract description 7
- 239000007787 solid Substances 0.000 claims abstract description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000003513 alkali Substances 0.000 claims abstract description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- WGNNILPYHCKCFF-UHFFFAOYSA-N 2-chloro-n-methylaniline Chemical group CNC1=CC=CC=C1Cl WGNNILPYHCKCFF-UHFFFAOYSA-N 0.000 claims description 7
- 238000004809 thin layer chromatography Methods 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 6
- SMVIAQFTVWDWDS-UHFFFAOYSA-N 2-bromo-n-methylaniline Chemical compound CNC1=CC=CC=C1Br SMVIAQFTVWDWDS-UHFFFAOYSA-N 0.000 claims description 4
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 4
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 4
- 229940045803 cuprous chloride Drugs 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 4
- 230000002194 synthesizing effect Effects 0.000 claims description 4
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims description 3
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 3
- 239000007795 chemical reaction product Substances 0.000 claims description 3
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 claims description 3
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 3
- 238000010025 steaming Methods 0.000 claims description 2
- 238000011031 large-scale manufacturing process Methods 0.000 abstract description 2
- ZBFZXENHYIJZGA-UHFFFAOYSA-N 2,3,4,4a-tetrahydrocarbazol-1-one Chemical compound C1=CC=C2C3CCCC(=O)C3=NC2=C1 ZBFZXENHYIJZGA-UHFFFAOYSA-N 0.000 description 12
- 239000002994 raw material Substances 0.000 description 8
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- -1 1,2,3, 9-tetrahydromethyl { (2-methylimidazol-1-yl) methyl } -4-oxocarbazole hydrochloride Chemical compound 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- MKBLHFILKIKSQM-UHFFFAOYSA-N 9-methyl-3-[(2-methyl-1h-imidazol-3-ium-3-yl)methyl]-2,3-dihydro-1h-carbazol-4-one;chloride Chemical compound Cl.CC1=NC=CN1CC1C(=O)C(C=2C(=CC=CC=2)N2C)=C2CC1 MKBLHFILKIKSQM-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229960000770 ondansetron hydrochloride Drugs 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 230000001515 vagal effect Effects 0.000 description 2
- FCPMCNMAPNVXSZ-UHFFFAOYSA-N CNC1=CC=CC=C1.[Cl] Chemical compound CNC1=CC=CC=C1.[Cl] FCPMCNMAPNVXSZ-UHFFFAOYSA-N 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 230000000723 chemosensory effect Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- HJSLFCCWAKVHIW-UHFFFAOYSA-N cyclohexane-1,3-dione Chemical compound O=C1CCCC(=O)C1 HJSLFCCWAKVHIW-UHFFFAOYSA-N 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000001640 nerve ending Anatomy 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
Landscapes
- Indole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone and a synthesis method thereof, wherein 2-cyclohexene-1-one is added into a reaction bottle with a stirrer and a thermometer, tetrabutylammonium tribromide is added in batches, heating and stirring are carried out, then 2-halogeno-N-methylaniline, alkali and a catalyst are sequentially added into the reaction bottle, stirring is carried out at a high temperature, TLC tracking reaction is carried out, filtering is carried out after cooling is carried out, the filtrate is distilled under reduced pressure, redundant 2-halogeno-N-methylaniline is distilled, and the rest solid is washed for a plurality of times by water, thus obtaining 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone. Compared with the prior art, the 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone prepared by the method has high purity, high yield, more than 93 percent and more than 99 percent, and is suitable for large-scale production.
Description
Technical Field
The invention relates to the field of chemical synthesis, in particular to 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone and a synthesis method thereof.
Background
Ondansetron hydrochloride, having the chemical name 1,2,3, 9-tetrahydromethyl { (2-methylimidazol-1-yl) methyl } -4-oxocarbazole hydrochloride, is a selective 5-hydroxytryptamine 3 (5-HT) 3 ) Receptor antagonists which can be used to antagonize 5-HT in peripheral vagal nerve endings and central chemosensory regions 3 The receptor can block the vomiting reflex caused by the factors such as chemotherapy, surgery and the like, which promote the release of 5-hydroxytryptamine by the small intestine chromatophiles and excite the vagal afferent nerves.
At present, tetrahydrocarbazolone (1) or 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone (2) is a key raw material for preparing ondansetron hydrochloride in industrial production, and the quality of the product directly determines the quality of a final product, but at present, the synthetic process of the tetrahydrocarbazolone or 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone is extensive, the yield is low, the quality of the synthetic product is poor, and the subsequent application range of the product is limited.
Chinese patent application number CN201710375453.6 discloses a method for synthesizing tetrahydrocarbazolone, and the synthetic route involved is shown in the following formula:
the synthesis route takes 1, 3-cyclohexanedione and aniline as raw materials, tetrahydrocarbazolone is obtained through two steps of reactions, and 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone is obtained through methylation reaction of the tetrahydrocarbazolone, raw materials and auxiliary materials used in the reaction comprise more than ten kinds of aluminum oxide, toluene, palladium acetate and the like, the raw materials and auxiliary materials are various, the catalyst is high in price, and the obtained tetrahydrocarbazolone also needs to pass through a silica gel column, so that the synthesis cost is increased, and the industrialization process is influenced.
Disclosure of Invention
The invention aims to solve the problems that 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone in the prior art has various raw materials and auxiliary materials, the catalyst is expensive, and a target product needs to pass through a silica gel column, and provides 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone and a synthesis method thereof.
In order to achieve the above purpose, the invention is implemented according to the following technical scheme:
the first object of the invention is to provide a synthesis method of 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone, which comprises the following steps:
s1, taking 2-cyclohexene-1-one and tetrabutylammonium tribromide in a weight ratio of 1:1.6-2, adding the 2-cyclohexene-1-one into a reaction bottle with a stirrer and a thermometer, adding the tetrabutylammonium tribromide into the reaction bottle for 3-5 times, heating to 75-85 ℃, and stirring for reaction for 2-5 hours;
s2, sequentially adding 3-5 times of 2-halogeno-N-methylaniline, 1.1-1.7 times of alkali and 0.002-0.012 times of catalyst of 2-cyclohexene-1-ketone into a reaction bottle of the reaction product of the step S1, heating to 110-120 ℃, stirring for 3-4H, tracking reaction by TLC, cooling, filtering, decompressing and distilling the filtrate, steaming out redundant 2-halogeno-N-methylaniline, and washing the rest solid at least 3 times by water to obtain 1,2,3, 4-tetrahydro-9-methyl-4H-carbazole ketone.
As a preferable technical scheme of the invention, the alkali is potassium carbonate or sodium carbonate.
As a preferable technical scheme of the invention, the 2-halogenated-N-methylaniline is 2-chloro-N-methylaniline or 2-bromo-N-methylaniline.
As a preferable technical scheme of the invention, the catalyst is one of cuprous chloride, cuprous bromide and cuprous iodide.
A second object of the present invention is to provide a 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone synthesized by the above synthesis method.
Compared with the prior art, the invention has the following beneficial effects:
1. according to the invention, tetrabutylammonium tribromide is used as a brominating reagent, and can be directly dissolved in raw materials to participate in reaction after being heated, no additional solvent is needed in the reaction, the method is environment-friendly and efficient, the reacted ammonium salt can be directly used as an acid binding agent in the next step without treatment, the cost is greatly saved, and the emission of three wastes is reduced;
2. the addition amount of the 2-bromo (chloro) -N-methylaniline is excessive, and the excessive addition amount can ensure that the 3-bromo-cyclohexane-1-ketone compound can completely react; secondly, 2-bromine (chlorine) -N-methylaniline is alkaline, can be used as an acid binding agent to neutralize HBr (HCl) generated by the reaction, and is favorable for fully carrying out the reaction; thirdly, excessive 2-bromo (chloro) -N-methylaniline can be used as a solvent, so that the problem of increased cost and secondary pollution caused by the use of other solvents in a reaction system is avoided;
3. the synthesis method has the advantages of easily obtained raw materials, convenient operation and mild reaction conditions, and the prepared 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone has high purity, high yield, more than 93 percent and more than 99 percent, and is suitable for large-scale production.
Drawings
FIG. 1 is a nuclear magnetic resonance hydrogen spectrum of 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone.
FIG. 2 is a nuclear magnetic carbon spectrum of 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone.
Detailed Description
The present invention will be described in further detail with reference to the following examples in order to make the objects, technical solutions and advantages of the present invention more apparent. The specific embodiments described herein are for purposes of illustration only and are not intended to limit the invention.
The reagents and raw materials used in the following examples were commercially available, and specific sources thereof were not described in detail unless otherwise specified.
The synthetic route of the 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone is as follows:
the synthetic procedure of the present invention is described in detail below by way of specific examples.
Example 1
Adding 1kg of 2-cyclohexene-1-one into a reaction bottle with a stirrer and a thermometer, adding 1.6kg of tetrabutylammonium tribromide in three batches, heating to 75 ℃ and stirring for reaction for 2 hours, then sequentially adding 3kg of 2-chloro-N-methylaniline, 1.1kg of potassium carbonate and 0.002kg of catalyst cuprous chloride into the reaction bottle, heating to 110 ℃, stirring for reaction for 3 hours, carrying out TLC tracking reaction, cooling after the reaction, filtering, distilling the filtrate under reduced pressure, distilling off redundant 2-chloro-N-methylaniline, and washing the rest solid with water for 3 times to obtain 1.83kg of 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone. In order to determine the molecular structure of the prepared 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone, nuclear magnetic resonance detection is carried out on the prepared 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone, and a nuclear magnetic hydrogen spectrogram and a nuclear magnetic carbon spectrogram are respectively shown in the figure 1 and the figure 2, and can be seen from the figure 1 and the figure 2: m.p.192.7-194.1 ℃; 1 H NMR(300MHz,DMSO-d 6 )δ:8.06~7.99(m,1H,-Ar-H),7.61~7.46(m, 1H,-Ar-H),7.38~7.09(m,2H,-Ar-H),3.70(s,3H,-CH 3 ),2.96(t,J=6.0 Hz,2H,-CH 2 -),2.39(t,J=5.8Hz,2H,-CH 2 -),2.17~2.01(m,2H,-CH 2 -); 13 C NMR(75MHz,DMSO-d 6 )δ:196.08,168.48,143.20,123.37,121.91,121.73, 119.78,119.56,110.97,39.12,30.57,22.29;HR(ESI)MS(m/z):[M+H] + :200.0993。
calculated, the weight ratio of the 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone actually obtained in the example to the compound theoretically obtained, namely, the yield, was 88.3%, and the HPLC purity was 97.5% as determined by high performance liquid chromatography analysis.
Example 2
Adding 1kg of 2-cyclohexene-1-one into a reaction bottle with a stirrer and a thermometer, adding 1.8kg of tetrabutylammonium tribromide in three batches, heating to 80 ℃ and stirring for reaction for 3 hours, then sequentially adding 4kg of 2-bromo-N-methylaniline, 1.5kg of potassium carbonate and 0.009kg of catalyst cuprous bromide into the reaction bottle, heating to 115 ℃ and stirring for reaction for 4 hours, carrying out TLC tracking reaction, cooling after the reaction, filtering, distilling the filtrate under reduced pressure, distilling off excessive 2-bromo-N-methylaniline, washing the rest solid with water for 4 times, obtaining 1.93kg of 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone, calculating the weight ratio of the 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone actually obtained in the embodiment to obtain the compound with the weight ratio of 93.2%, and obtaining the compound with the purity of 99.1% through high performance liquid chromatography analysis.
Example 3
Adding 1kg of 2-cyclohexene-1-one into a reaction bottle with a stirrer and a thermometer, adding 2.0kg of tetrabutylammonium tribromide into five batches, heating to 85 ℃ and stirring for reaction for 5 hours, then sequentially adding 5kg of 2-chloro-N-methylaniline, 1.7kg of sodium carbonate and 0.012kg of catalyst cuprous iodide into the reaction bottle, heating to 120 ℃ and stirring for reaction for 3.5 hours, carrying out TLC tracking reaction, cooling and filtering the reaction product, decompressing and distilling the filtrate, distilling the excessive 2-halogeno-N-methylaniline, washing the residual solid with water for 5 times, and obtaining 1.88kg of 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone, wherein the weight ratio of the compound actually obtained in the embodiment to the theoretical weight ratio is 90.7%, and the purity is 98.4% by HPLC (high performance liquid chromatography).
Example 4
Adding 1kg of 2-cyclohexene-1-one into a reaction bottle with a stirrer and a thermometer, adding 1.8kg of tetrabutylammonium tribromide in four batches, heating to 80 ℃ and stirring for reaction for 4 hours, then sequentially adding 4kg of 2-chloro-N-methylaniline, 1.5kg of sodium carbonate and 0.009kg of catalyst cuprous chloride into the reaction bottle, heating to 110 ℃, stirring for reaction for 3 hours, carrying out TLC tracking reaction, cooling after the reaction is finished, filtering, distilling filtrate under reduced pressure, distilling off excessive 2-chloro-N-methylaniline, washing the residual solid with water for 6 times, obtaining 1.85kg of 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone, calculating the weight ratio of the 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone actually obtained in the embodiment to obtain the compound with the weight ratio of 89.2%, and obtaining the compound with the purity of 98.1% through high performance liquid chromatography analysis.
The technical scheme of the invention is not limited to the specific embodiment, and all technical modifications made according to the technical scheme of the invention fall within the protection scope of the invention.
Claims (4)
1. The synthesis method of the 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone is characterized by comprising the following steps of:
s1, taking 2-cyclohexene-1-one and tetrabutylammonium tribromide in a weight ratio of 1:1.6-2, adding the 2-cyclohexene-1-one into a reaction bottle with a stirrer and a thermometer, adding the tetrabutylammonium tribromide into the reaction bottle for multiple times, heating to 75-85 ℃, and stirring for reaction for 2-5 hours;
s2, sequentially adding 3-5 times of 2-halogeno-N-methylaniline, 1.1-1.7 times of alkali and 0.002-0.012 times of catalyst of 2-cyclohexene-1-ketone into a reaction bottle of the reaction product of the step S1, heating to 110-120 ℃, stirring for 3-4H, tracking reaction by TLC, cooling, filtering, decompressing and distilling the filtrate, steaming out redundant 2-halogeno-N-methylaniline, and washing the rest solid with water at least three times to obtain 1,2,3, 4-tetrahydro-9-methyl-4H-carbazole ketone.
2. The method for synthesizing 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone according to claim 1, wherein: the alkali is potassium carbonate or sodium carbonate.
3. The method for synthesizing 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone according to claim 1, wherein: the 2-halogeno-N-methylaniline is 2-chloro-N-methylaniline or 2-bromo-N-methylaniline.
4. The method for synthesizing 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone according to claim 1, wherein: the catalyst is one of cuprous chloride, cuprous bromide and cuprous iodide.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202211355015.0A CN115677561B (en) | 2022-11-01 | 2022-11-01 | 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone and synthesis method thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202211355015.0A CN115677561B (en) | 2022-11-01 | 2022-11-01 | 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone and synthesis method thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
CN115677561A CN115677561A (en) | 2023-02-03 |
CN115677561B true CN115677561B (en) | 2024-04-05 |
Family
ID=85047960
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202211355015.0A Active CN115677561B (en) | 2022-11-01 | 2022-11-01 | 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone and synthesis method thereof |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN115677561B (en) |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1089941A (en) * | 1992-10-14 | 1994-07-27 | 格德昂·理查德化学工厂股份公司 | Carbazolone derivative and preparation method thereof |
CN1733698A (en) * | 2005-08-29 | 2006-02-15 | 浙江工业大学 | 1,2,3,9-tetrahydro-9-methyl-4H-carbazole-4-one preparation method |
CN101914056A (en) * | 2010-08-12 | 2010-12-15 | 天津大学 | Preparation method of N-alkyl substituted tetrahydro-carbazolone derivative |
CN102464604A (en) * | 2010-11-09 | 2012-05-23 | 哈尔滨理工大学 | Production method of 1,2,3,4-tetrahydro-9-methylcarbazol-4-one |
CN102850259A (en) * | 2012-09-21 | 2013-01-02 | 天津狄克特科技有限公司 | Preparation method for 6-halogen substituted-1,2,3,4-terahydrocarbazole intermediate of anti-hepatitis c drugs |
CN103497144A (en) * | 2013-10-01 | 2014-01-08 | 迪沙药业集团山东迪沙药业有限公司 | Preparation method of carbazol ketone tetrahydride |
CN107235891A (en) * | 2017-05-24 | 2017-10-10 | 北京八亿时空液晶科技股份有限公司 | A kind of preparation method of 4 bromine carbazole |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2398071B (en) * | 2003-01-24 | 2006-06-07 | Synthon Bv | Process for making ondansetron and intermediate thereof |
-
2022
- 2022-11-01 CN CN202211355015.0A patent/CN115677561B/en active Active
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1089941A (en) * | 1992-10-14 | 1994-07-27 | 格德昂·理查德化学工厂股份公司 | Carbazolone derivative and preparation method thereof |
CN1733698A (en) * | 2005-08-29 | 2006-02-15 | 浙江工业大学 | 1,2,3,9-tetrahydro-9-methyl-4H-carbazole-4-one preparation method |
CN101914056A (en) * | 2010-08-12 | 2010-12-15 | 天津大学 | Preparation method of N-alkyl substituted tetrahydro-carbazolone derivative |
CN102464604A (en) * | 2010-11-09 | 2012-05-23 | 哈尔滨理工大学 | Production method of 1,2,3,4-tetrahydro-9-methylcarbazol-4-one |
CN102850259A (en) * | 2012-09-21 | 2013-01-02 | 天津狄克特科技有限公司 | Preparation method for 6-halogen substituted-1,2,3,4-terahydrocarbazole intermediate of anti-hepatitis c drugs |
CN103497144A (en) * | 2013-10-01 | 2014-01-08 | 迪沙药业集团山东迪沙药业有限公司 | Preparation method of carbazol ketone tetrahydride |
CN107235891A (en) * | 2017-05-24 | 2017-10-10 | 北京八亿时空液晶科技股份有限公司 | A kind of preparation method of 4 bromine carbazole |
Also Published As
Publication number | Publication date |
---|---|
CN115677561A (en) | 2023-02-03 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN112079742B (en) | Method for preparing lidocaine through continuous reaction | |
CN108892669A (en) | A method of preparing 2- amido-6-chloropurine | |
WO2021152435A1 (en) | Process for preparation of 5-bromo-1, 2, 3-trichlorobenzene | |
CN115677561B (en) | 1,2,3, 4-tetrahydro-9-methyl-4H-carbazolone and synthesis method thereof | |
CN107056590B (en) | Industrial method for preparing and purifying 4, 4' -dimethoxy triphenylchloromethane | |
CN115504870B (en) | Preparation method and application of 4-methoxy-2-naphthol | |
CN110698352A (en) | Synthetic method of 3-bromo-5-aminocatechol dimethyl ether | |
CN111217690B (en) | Preparation method of propafenone hydrochloride and intermediate 2' -hydroxy dihydrochalcone thereof | |
CN111100042B (en) | Preparation method of 2-methoxy-5-sulfonamide benzoic acid | |
CN111303045A (en) | Production process of 2-ethoxy-4, 6-difluoropyrimidine | |
JP2000109462A (en) | Production of 8-benzylaminoquioline | |
JPS62192389A (en) | 1,1-dichloro-1,2,2,-trimethyl-2-phenyldisilane and production thereof | |
CN114835589B (en) | Preparation method of 2,4-difluoro-3,5-dichloroaniline | |
CN115260092B (en) | Synthesis method of 2-chloronicotinamide and N-substituted derivative thereof | |
CN114773312B (en) | Preparation process of alolol hydrochloride intermediate | |
CN112079764B (en) | Synthesis method of sunitinib intermediate 5-fluoroindol-2-one | |
CN110963967B (en) | Preparation method of 2-methyl-4-aminoquinoline | |
CN113382982B (en) | Preparation method of siponimod | |
CN112745205B (en) | Preparation method of simod intermediate | |
JP3282357B2 (en) | Piperonal manufacturing method | |
CN116924975A (en) | Preparation method of 2-amino-5-fluoropyridine | |
CN116621710A (en) | Synthesis method of cyclopropylamine | |
CN117946013A (en) | Method for synthesizing 5, 6-dihalogen-3-aminopyrazine-2-methyl formate by one-pot method | |
CN115677559A (en) | One-step synthesis method of ondansetron intermediate tetrahydrocarbazolone | |
CN116803991A (en) | Method for preparing saflufenacil intermediate |
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 | ||
GR01 | Patent grant | ||
GR01 | Patent grant |