CN102924359B - Method for synthesizing substituted indole compounds through one-pot method - Google Patents
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Abstract
The invention relates to a synthesis method of substituted indole compounds, and particularly relates to a method for synthesizing substituted indole compounds through a one-pot method. The method comprises the following steps: under alkaline and anaerobic conditions, reacting ortho-nitrotoluene derivatives and N,N-dimethylformamide dimethyl acetal or triethyl orthoformate used as raw materials in an organic solvent; and then, adding a reducer, and performing reduction and cyclization reaction to obtain indole derivatives, wherein R is a monosubstitution or polysubstitution located on site 4, 5, 6 or 7; and the R substituent is hydrogen, alkyl, substituted alkyl, alkoxy, amino or halogen atom. According to the invention, a one-pot method is adopted; the conventional and readily accessible ortho-nitrotoluene compounds are directly used as raw materials for reaction; separation and purification of intermediate compounds are not required; and the indole derivatives can be synthesized through the one-pot method by effectively controlling the reaction conditions, the charging sequence and the charging ratio. According to the invention, the technological operation procedure is simplified, the reaction time is shortened, the cost is saved, the total yield is improved, and better production and practical values can be achieved.
Description
Technical field
The present invention relates to the synthetic method of substituent indole compound, specifically a kind of method of one pot process substituent indole compound.
Background technology
Benzazole compounds is widespread in nature, and many phenyl ring all have biological activity containing substituent indoles, and indoles and derivative thereof or a kind of important industrial chemicals, be widely used in the various fields such as medicine, agricultural chemicals, dyestuff, food and spices.Melatonin has another name called brain platinum, and produce primarily of 5-methoxy-Indole, it directly acts on hypothalamus, has and promotes sleep, endocrine regulation, the multiple physiological action such as strengthening immunity.Indomethacin can grow at the fibroblast like synoviocyte (FLS) not affecting rheumatoid arthritis people, play anti-inflammatory action by suppressing mRNA, the protein expression two of the cytokines such as the IL-6 in FLS.The bromo-N of isolated indoles alkaloid 5,6-bis-from marine natural product, N-Dimethyltryptamine then shows antidepressant effect significantly.
Benzazole compounds is widely used, closely related with the life of people.But because production cost is high, market value height not under, therefore the research of synthesis of indole is very important, in recent years, it is gentle that people are finding reaction conditions always, effectively, method Fischer method (the Nagasaka T. of easy this compounds of synthesis, et al.Heterocycles1977,8:371-376) be one of the most general method of synthesis of indole and derivative thereof, it is with Al
2o
3for catalyzer, make the phenylhydrazone of aldehyde that deamination condensation reaction occur in benzole soln, form indole ring.The temperature of reaction of the method is relatively high, and by product is more, and productive rate is not high; The chloroacetylation method (Tsutomu S., et al.J.Org.Chem.1979,44 (4): 578-582) of aniline is raw material with aniline, at AlCl
3catalysis under, with BCl
3and ClCH
2cN reacts, and middle experience one is containing B
+cyclic transition state, acidifying obtains 2-amino-α-chloracetyl benzene, then in dioxane, uses NaBH
4reduce to obtain benzazolyl compounds, although the method step is simple, yield is on the low side; Organotin reagent and the palladium chtalyst crosslinking reaction of various electrophilic reagent are widely used in being connected thiazolinyl on aromatic ring, are the ideal methods of synthesis substituted indole, the method organo-metallic as catalyzer, as Pd (Ph
3p)
4, PdCl
2, RuCl
2(PPh
3)
3deng, organo-metallic is being widely used in producing indole derivatives in recent ten years, but the problem that ubiquity yield is not high, and the raw material that adopts of the method had and catalyzer expensive, not easily realize industrialization.
Summary of the invention
The object of the invention is a kind of method providing one pot process substituent indole compound.
The technical solution used in the present invention is for achieving the above object:
A kind of method of one pot process substituent indole compound, with Ortho Nitro Toluene derivative and N, dinethylformamide dimethylacetal or triethyl orthoformate are raw material, under alkaline oxygen free condition, react in organic solvent, then add that reductive agent carries out reducing, cyclization, namely obtain indole derivatives
wherein, R is positioned at 4,5,6,7 monosubstituted or polysubstituted; R substituent is hydrogen, alkyl, substituted hydrocarbon radical, alkoxyl group, amino or halogen atom.
The reaction formula of described synthetic method is:
Described with Ortho Nitro Toluene derivative and N, dinethylformamide dimethylacetal or triethyl orthoformate are raw material, under alkaline oxygen free condition, reaction 4-22h is carried out in organic solvent with 50-150 DEG C, then add reductive agent 25-60 DEG C carry out reducing, cyclization 0.5-2.5h, namely obtain indole derivatives; The mol ratio of described Ortho Nitro Toluene derivative, DMF dimethylacetal and alkali is 1:1-5:3-10; The mol ratio of Ortho Nitro Toluene derivative, triethyl orthoformate and alkali is 1:1-1.5:3-10.
Described add reductive agent 40-50 DEG C carry out reducing, cyclization 1-2h obtains indole derivatives.
Described reduction, cyclization products therefrom are by extraction, and the method for recrystallization is separated, purifying.The solvent used in described recrystallization purifying method is the mixed solvent of polar solvent and non-polar solvent.
Described alkali is the one in tetramethyleneimine, hexahydropyridine, piperazine, morpholine, quadrol or triethylamine.
Described organic solvent is DMF, toluene, benzene, a trimethylbenzene, tetrahydrofuran (THF), Isosorbide-5-Nitrae-dioxane, the one in condensed ethandiol dme or morpholine.
Described former dose is Raney's nickel and hydrazine, palladium carbon hydrogenation, tin protochloride, V-Brite B, iron-acetic acid or titanous chloride.Described reductive agent is 1-5:1 with the amount of substance ratio of Ortho Nitro Toluene derivative.
Beneficial effect of the present invention:
1. the present invention is directly raw material by Ortho Nitro Toluene compounds that is conventional, that be easy to get with " one kettle way " reaction, without the need to being separated, being purified into intermediate, by effectively controlling reaction conditions, order of addition(of ingredients) and ratio, directly reductive agent is added in same reaction vessel, reduction, cyclisation obtain the derivative of indoles, one pot reaction synthesis of indole derivative.
2. the present invention adopts " one kettle way ", without the need to separation of intermediates, thus simplifies technical operation flow; Shorten the reaction times; Save cost, improve the overall yield of reaction.
3. the present invention is easy and simple to handle, and reaction conditions is gentle, and suitability is wide, can be used for the synthesis of multiple substituent indole derivatives.
Embodiment
The following examples better will illustrate the present invention, but it is emphasized that the invention is not restricted to content represented by embodiment.
The method of synthesis substituent indole compound is to replace Ortho Nitro Toluene and N, dinethylformamide dimethylacetal or triethyl orthoformate are raw material, under alkaline oxygen free condition, react in organic solvent, the intermediate generated is without separation, and direct reducer carries out reducing, cyclization obtains indole derivatives.Wherein reaction formula is:
In formula, R can be positioned at 4,5,6,7, and R can be the one in hydrogen, alkyl or substituted hydrocarbon radical, alkoxyl group, amino, halogen atom, can be a substituting group or multiple substituting group.Also original reagent all adopts the slow mode sample introduction dripped;
Embodiment 1
Compd A: add trimethylbenzene between 50ml in 100ml there-necked flask; raw material 1(4-Chloro-2-Nitrobenzene, lower same) (0.69g, 4mmol); N; dinethylformamide dimethylacetal (0.95g, 8mmol), tetramethyleneimine (1.14g; 16mmol); nitrogen protection, fully stirs, and substrate is dissolved completely.Be warming up to 145 DEG C, condensing reflux, reaction process TLC follows the tracks of, until thin-layer chromatography display raw material point disappears, and cool to room temperature.Add the palladium carbon of catalytic amount (20mg) subsequently, and pass into hydrogen (10ml/min), control temperature of reaction at 45-50 DEG C, react and be cooled to room temperature after 2 hours, suction filtration, filter residue with dichloromethane rinse several times, extraction, recrystallization (hexanaphthene: methylene dichloride: methyl alcohol=2:1:8(v/v)) obtain off-white color solid, yield 92.3%.
The same compd A of preparation method of compd B-H, its feed ratio is identical with compound 1, compd B (productive rate 80.1%) can be obtained respectively, Compound C (productive rate 81.7%), Compound D (productive rate 79.4%), compd E (productive rate 69.6%), compound F 17-hydroxy-corticosterone (productive rate 92.6%), compound G(productive rate 87.4%), compound H (productive rate 84.0%), Compound I (productive rate 85.2%), compound J(productive rate 90.2%), compound K (productive rate 65.4%), compound L (productive rate 79.3%), compound M(productive rate 90.2%), compound N (productive rate 87.6%).
Embodiment 2:
Compd A: add 50ml DMF (DMF) in 100ml there-necked flask, raw material 1(0.69g, 4mmol); DMF dimethylacetal (0.95g, 8mmol), tetramethyleneimine (1.14g; 16mmol), nitrogen protection, fully stirs, and substrate is dissolved completely.Be warming up to 130 DEG C, condensing reflux, reaction process TLC follows the tracks of, until thin-layer chromatography display raw material point disappears, and cool to room temperature.Add the Raney's nickel of catalytic amount (100mg) subsequently, hydrazine hydrate (the 0.35g of 85% is slowly instilled with dropping funnel, 6mmol), be warming up to 30 DEG C, added the hydrazine hydrate of identical amount every 30 minutes, control temperature of reaction at 45-50 DEG C, TLC follows the tracks of, until the component point of thin-layer chromatography display intermediate product disappears, be cooled to room temperature, catalyzer diatomite filtration removing (can not drain in case catalyzer spontaneous combustion).Filter residue with dichloromethane rinse several times, extraction, recrystallization (hexanaphthene: methylene dichloride: methyl alcohol=2:1:8) obtains off-white color solid, yield 88.1%.
Raw material 1 is replaced with raw material 2-14, its feed ratio is identical with compound 1, compd B (productive rate 90.1%) can be obtained respectively, Compound C (productive rate 88.7%), Compound D (productive rate 90.2%), compd E (productive rate 89.6%), compound F 17-hydroxy-corticosterone (productive rate 82.6%), compound G(productive rate 77.4%), compound H (productive rate 82.0%), Compound I (productive rate 83.2%), compound J(productive rate 90.1%), compound K (productive rate 64.3%), compound L (productive rate 86.3%), compound M(productive rate 91.1%), compound N (productive rate 78.6%).
Embodiment 3:
Compd A: add 50ml tetrahydrofuran (THF) (THF) in 100ml there-necked flask, raw material 1(0.69g, 4mmol), N; dinethylformamide dimethylacetal (0.95g, 8mmol), tetramethyleneimine (1.14g, 16mmol); nitrogen protection, fully stirs, and substrate is dissolved completely.Be warming up to 80 DEG C, condensing reflux, reaction process TLC follows the tracks of, until thin-layer chromatography display raw material point disappears, and cool to room temperature.Add ferrous acetate (1.4g subsequently, 8mmol), control temperature of reaction to follow the tracks of at 45-50 DEG C, TLC, until the component point of thin-layer chromatography display intermediate product disappears, be cooled to room temperature, suction filtration, filter residue with dichloromethane rinse several times, extraction, recrystallization (hexanaphthene: methylene dichloride: methyl alcohol=2:1:8) obtains off-white color solid, yield 78.5%.
Raw material 1 is replaced with raw material 2-14, its feed ratio is identical with compound 1, compd B (productive rate 77.5%) can be obtained respectively, Compound C (productive rate 78.3%), Compound D (productive rate 80.4%), compd E (productive rate 79.2%), compound F 17-hydroxy-corticosterone (productive rate 76.6%), compound G(productive rate 72.4%), compound H (productive rate 80.3%), Compound I (productive rate 76.7%), compound J(productive rate 82.3%), compound K (productive rate 57.9%), compound L (productive rate 74.3%), compound M(productive rate 80.4%), compound N (productive rate 63.5%).
Embodiment 4:
Compd A: add 50ml condensed ethandiol dme in 100ml there-necked flask, raw material 1(0.69g, 4mmol), N; dinethylformamide dimethylacetal (0.95g, 8mmol), piperazine (1.03g, 12mmol); nitrogen protection, fully stirs, and substrate is dissolved completely.Be warming up to 135 DEG C, condensing reflux, reaction process TLC follows the tracks of, until thin-layer chromatography display raw material point disappears, and cool to room temperature.Add tin protochloride (1.8g subsequently, 8mmol), control temperature of reaction to follow the tracks of at 45-50 DEG C, TLC, until the component point of thin-layer chromatography display intermediate product disappears, be cooled to room temperature, suction filtration, filter residue with dichloromethane rinse several times, extraction, recrystallization (hexanaphthene: methylene dichloride: methyl alcohol=2:1:8) obtains off-white color solid, yield 90.3%.
Raw material 1 is replaced with raw material 2-14, its feed ratio is identical with compound 1, compd B (productive rate 92.1%) can be obtained respectively, Compound C (productive rate 90.7%), Compound D (productive rate 87.2%), compd E (productive rate 85.6%), compound F 17-hydroxy-corticosterone (productive rate 81.7%), compound G(productive rate 72.3%), compound H (productive rate 85.4%), Compound I (productive rate 90.1%), compound J(productive rate 83.9%), compound K (productive rate 72.5%), compound L (productive rate 90.4%), compound M(productive rate 89.5%), compound N (productive rate 84.8%).
Embodiment 5:
Compd A: the mixed solvent (toluene: dioxane=3:1) adding 50ml in 100ml there-necked flask; raw material 1(0.69g; 4mmol), DMF dimethylacetal (0.95g; 8mmol); piperazine (1.03g, 12mmol), nitrogen protection; abundant stirring, makes substrate dissolve completely.Be warming up to 101 DEG C, logical condensate return, uses TLC tracking reaction process, until thin-layer chromatography display raw material point disappears, and cool to room temperature.Add V-Brite B (1.4g subsequently, 8mmol), control temperature of reaction to follow the tracks of at 45-50 DEG C, TLC, until thin-layer chromatography display intermediate product component point disappears, be cooled to room temperature, suction filtration, filter residue with dichloromethane rinse several times, extraction, recrystallization (hexanaphthene: methylene dichloride: methyl alcohol=2:1:8) obtains off-white color solid, yield 85.4%.
Raw material 1 is replaced with raw material 2-14, its feed ratio is identical with compound 1, compd B (productive rate 87.1%) can be obtained respectively, Compound C (productive rate 78.7%), Compound D (productive rate 88.9%), compd E (productive rate 82.4%), compound F 17-hydroxy-corticosterone (productive rate 79.8%), compound G(productive rate 75.2%), compound H (productive rate 86.3%), Compound I (productive rate 78.2%), compound J(productive rate 86.3%), compound K (productive rate 60.2%), compound L (productive rate 80.9%), compound M(productive rate 87.1%), compound N (productive rate 83.2%).
Embodiment 6:
Compd A: add 50ml morpholine in 100ml there-necked flask, raw material 1(0.69g, 4mmol), DMF dimethylacetal (0.95g, 8mmol), nitrogen protection, fully stirs, and substrate is dissolved completely.Be warming up to 120 DEG C, logical condensate return, reaction process TLC follows the tracks of, until thin-layer chromatography display raw material point disappears, and cool to room temperature.Add titanous chloride (1.2g subsequently, 8mmol), control temperature of reaction to follow the tracks of at 45-50 DEG C, TLC, until thin-layer chromatography display intermediate product component point disappears, be cooled to room temperature, suction filtration, filter residue with dichloromethane rinse several times, extraction, recrystallization (hexanaphthene: methylene dichloride: methyl alcohol=2:1:8) obtains off-white color solid, yield 92.1%.
Raw material 1 is replaced with raw material 2-14, its feed ratio is identical with compound 1, compd B (productive rate 91.3%) can be obtained respectively, Compound C (productive rate 90.7%), Compound D (productive rate 89.2%), compd E (productive rate 90.4%), compound F 17-hydroxy-corticosterone (productive rate 87.5%), compound G(productive rate 76.8%), compound H (productive rate 87.6%), Compound I (productive rate 79.4%), compound J(productive rate 88.5%), compound K (productive rate 70.5%), compound L (productive rate 91.1%), compound M(productive rate 86.9%), compound N (productive rate 88.4%).
Embodiment 7:
Compd A: add trimethylbenzene between 50ml in 100ml there-necked flask, raw material 1(0.69g, 4mmol), triethyl orthoformate (0.60g, 4mmol), tetramethyleneimine (1.14g, 16mmol), nitrogen protection, fully stirs, and substrate is dissolved completely.Be warming up to 145 DEG C, logical condensate return, reaction process TLC follows the tracks of, until thin-layer chromatography display raw material point disappears, and cool to room temperature.Add the palladium carbon of catalytic amount (50mg) subsequently, and pass into hydrogen (10ml/min), control temperature of reaction at 45-50 DEG C, react and be cooled to room temperature after 2 hours, suction filtration, filter residue with dichloromethane rinse several times, extraction, recrystallization (hexanaphthene: methylene dichloride: methyl alcohol=2:1:8) obtains off-white color solid, yield 87.3%.
Raw material 1 is replaced with raw material 2-14, its feed ratio is identical with compound 1, compd B (productive rate 82.3%) can be obtained respectively, Compound C (productive rate 90.2%), Compound D (productive rate 84.5%), compd E (productive rate 74.3%), compound F 17-hydroxy-corticosterone (productive rate 88.5%), compound G(productive rate 90.2%), compound H (productive rate 79.8%), Compound I (productive rate 84.9%), compound J(productive rate 89.5%), compound K (productive rate 72.0%), compound L (productive rate 84.2%), compound M(productive rate 87.5%), compound N (productive rate 75.9%).
Embodiment 8:
Compd A: add 50ml DMF (DMF) in 100ml there-necked flask, raw material 1(0.69g, 4mmol); triethyl orthoformate (0.60g, 4mmol), pyridine (1.27g, 16mmol); nitrogen protection, fully stirs, and substrate is dissolved completely.Be warming up to 130 DEG C, logical condensate return, reaction process TLC follows the tracks of, until thin-layer chromatography display raw material point disappears, and cool to room temperature.Add the Raney's nickel of catalytic amount (100mg) subsequently, hydrazine hydrate (the 0.35g of 85% is slowly instilled with dropping funnel, 6mmol), be warming up to 30 DEG C, added the hydrazine hydrate of identical amount every 30 minutes, control temperature of reaction at 45-50 DEG C, TLC follows the tracks of, until thin-layer chromatography display intermediate product component point disappears, be cooled to room temperature, catalyzer diatomite filtration removing (can not drain in case catalyzer spontaneous combustion).Filter residue with dichloromethane rinse several times, extraction, recrystallization (hexanaphthene: methylene dichloride: methyl alcohol=2:1:8) obtains off-white color solid, yield 90.2%.
Raw material 1 is replaced with raw material 2-14, its feed ratio is identical with compound 1, compd B (productive rate 80.1%) can be obtained respectively, Compound C (productive rate 84.7%), Compound D (productive rate 86.2%), compd E (productive rate 74.4%), compound F 17-hydroxy-corticosterone (productive rate 86.9%), compound G(productive rate 84.7%), compound H (productive rate 75.2%), Compound I (productive rate 90.2%), compound J(productive rate 87.7%), compound K (productive rate 71.1%), compound L (productive rate 80.6%), compound M(productive rate 87.6%), compound N (productive rate 71.4%).
Embodiment 9:
Compd A: add 50ml tetrahydrofuran (THF) (THF) in 100ml there-necked flask, raw material 1(0.69g, 4mmol), triethyl orthoformate (0.60g, 4mmol), triethylamine (1.62g, 16mmol), nitrogen protection, fully stirs, and substrate is dissolved completely.Be warming up to 80 DEG C, logical condensate return, reaction process TLC follows the tracks of, until thin-layer chromatography display raw material point disappears, and cool to room temperature.Add ferrous acetate (1.4g subsequently, 8mmol), control temperature of reaction to follow the tracks of at 45-50 DEG C, TLC, until thin-layer chromatography display intermediate product component point disappears, be cooled to room temperature, suction filtration, filter residue with dichloromethane rinse several times, extraction, recrystallization (hexanaphthene: methylene dichloride: methyl alcohol=2:1:8) obtains off-white color solid, yield 82.4%.
Raw material 1 is replaced with raw material 2-14, its feed ratio is identical with compound 1, compd B (productive rate 79.1%) can be obtained respectively, Compound C (productive rate 77.7%), Compound D (productive rate 69.4%), compd E (productive rate 71.6%), compound F 17-hydroxy-corticosterone (productive rate 83.3%), compound G(productive rate 69.4%), compound H (productive rate 73.2%), Compound I (productive rate 66.8%), compound J(productive rate 67.5%), compound K (productive rate 55.8%), compound L (productive rate 71.1%), compound M(productive rate 80.4%), compound N (productive rate 70.3%).
Embodiment 10:
Compd A: add 50ml morpholine in 100ml there-necked flask, raw material 1(0.69g, 4mmol), triethyl orthoformate (0.60g, 4mmol), nitrogen protection, fully stirs, and substrate is dissolved completely.Be warming up to 120 DEG C, logical condensate return, reaction process TLC follows the tracks of, until thin-layer chromatography display raw material point disappears, and cool to room temperature.Add the Raney's nickel of catalytic amount (100mg) subsequently, hydrazine hydrate (the 0.35g of 85% is slowly instilled with dropping funnel, 6mmol), be warming up to 30 DEG C, added the hydrazine hydrate of identical amount every 30 minutes, control temperature of reaction at 45-50 DEG C, TLC follows the tracks of, until thin-layer chromatography display intermediate product component point disappears, be cooled to room temperature, catalyzer diatomite filtration removing (can not drain in case catalyzer spontaneous combustion).Filter residue with dichloromethane rinse several times, extraction, recrystallization (hexanaphthene: methylene dichloride: methyl alcohol=2:1:8) obtains off-white color solid, yield 86.1%.
Raw material 1 is replaced with raw material 2-14, its feed ratio is identical with compound 1, compd B (productive rate 87.2%) can be obtained respectively, Compound C (productive rate 78.9%), Compound D (productive rate 81.3%), compd E (productive rate 74.4%), compound F 17-hydroxy-corticosterone (productive rate 87.8%), compound G(productive rate 91.5%), compound H (productive rate 78.0%), Compound I (productive rate 88.4%), compound J(productive rate 82.5%), compound K (productive rate 66.1%), compound L (productive rate 87.2%), compound M(productive rate 79.3%), compound N (productive rate 74.2%).
Claims (6)
1. a method for one pot process substituent indole compound, is characterized in that:
With Ortho Nitro Toluene derivative and N, dinethylformamide dimethylacetal or triethyl orthoformate are raw material, under alkaline oxygen free condition, reaction 4-22h is carried out in organic solvent with 50-150 DEG C, then add reductive agent 25-60 DEG C carry out reducing, cyclization 0.5-2.5h, namely obtain indole derivatives
the mol ratio of described Ortho Nitro Toluene derivative and DMF dimethylacetal and alkali is 1:1-5:3-10; The mol ratio of Ortho Nitro Toluene derivative and triethyl orthoformate and alkali is 1:1-1.5:3-10;
Wherein, R is positioned at 4,5,6,7 monosubstituted or polysubstituted; R substituent is hydrogen, alkyl, substituted hydrocarbon radical, alkoxyl group, amino or halogen atom;
Described organic solvent is DMF, toluene, benzene, a trimethylbenzene, tetrahydrofuran (THF), Isosorbide-5-Nitrae-dioxane, the one in condensed ethandiol dme or morpholine;
Described reductive agent is Raney's nickel and hydrazine, palladium carbon hydrogenation, tin protochloride, V-Brite B, iron-acetic acid or titanous chloride.
2., by the method for one pot process substituent indole compound according to claim 1, it is characterized in that: the reaction formula of described synthetic method is:
3., by the method for one pot process substituent indole compound according to claim 1, it is characterized in that: described in add reductive agent 40-50 DEG C carry out reducing, cyclization 1-2h obtains indole derivatives.
4. by the method for one pot process substituent indole compound according to claim 1, it is characterized in that: described reduction, cyclization products therefrom are by extraction, and the method for recrystallization is separated, purifying.
5., by the method for one pot process substituent indole compound according to claim 1, it is characterized in that: described alkali is the one in tetramethyleneimine, hexahydropyridine, piperazine, morpholine, quadrol or triethylamine.
6. by the method for one pot process substituent indole compound according to claim 1, it is characterized in that: described reductive agent is 1-5:1 with the amount of substance ratio of Ortho Nitro Toluene derivative.
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4590280A (en) * | 1985-03-15 | 1986-05-20 | The Upjohn Company | Preparing indoline derivatives |
| CN1527816A (en) * | 2001-06-07 | 2004-09-08 | - | New indole derivatives with 5-HT6 receptor affinity |
| CN1911912A (en) * | 2006-08-30 | 2007-02-14 | 天津大学 | Synthesis method of indole |
| CN101250154A (en) * | 2008-03-13 | 2008-08-27 | 台州市知青化工有限公司 | Industrial production method of 6-fluoroindo |
| CN101544589A (en) * | 2009-05-08 | 2009-09-30 | 上海泰坦化学有限公司 | Preparation for medicinal intermediate 6-chloro-5-fluroindole for synthesizing anti-cancer medicament |
| CN102746211A (en) * | 2012-06-27 | 2012-10-24 | 上海泰坦化学有限公司 | Method for preparing substituted indole-3-methanal compound |
-
2012
- 2012-10-30 CN CN201210423969.0A patent/CN102924359B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4590280A (en) * | 1985-03-15 | 1986-05-20 | The Upjohn Company | Preparing indoline derivatives |
| CN1527816A (en) * | 2001-06-07 | 2004-09-08 | - | New indole derivatives with 5-HT6 receptor affinity |
| CN1911912A (en) * | 2006-08-30 | 2007-02-14 | 天津大学 | Synthesis method of indole |
| CN101250154A (en) * | 2008-03-13 | 2008-08-27 | 台州市知青化工有限公司 | Industrial production method of 6-fluoroindo |
| CN101544589A (en) * | 2009-05-08 | 2009-09-30 | 上海泰坦化学有限公司 | Preparation for medicinal intermediate 6-chloro-5-fluroindole for synthesizing anti-cancer medicament |
| CN102746211A (en) * | 2012-06-27 | 2012-10-24 | 上海泰坦化学有限公司 | Method for preparing substituted indole-3-methanal compound |
Non-Patent Citations (6)
| Title |
|---|
| 4-溴吲哚-3-甲醛的合成;葛裕华，等;《合成化学》;20050317;第13卷(第1期);第94页第1.3、1.4节 * |
| 4-硝基吲哚的合成研究;何光洪;《科学技术与工程》;20090131;第9卷(第2期);全文 * |
| 6-氨基-3-取代吲哚的合成和生物活性研究;李清寒，等;《化学研究与应用》;20080331;第20卷(第3期);第348-351页，具体参见第349页第1.2节 * |
| Practical Methodologies for the Synthesis of Indoles;Guy R. Humphrey，等;《Chemical Reviews》;20060706;第106卷(第7期);第2875-2911页，具体参见第2897页scheme2、scheme3 * |
| Synthesis of 4-Azidoindole-3-acetic Acid, a Photoprobe Causing Sustained Auxin Activity;L. Lee Melhado，等;《J.Org.Chem》;19881231;第53卷(第16期);全文 * |
| 取代吲哚-3-甲醛类化合物的合成;葛裕华，等;《有机化学》;20061231;第26卷(第4期);第563-567页，具体参见第564页1.2节 * |
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