CN102924359A - 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 the method for the synthetic substituent indole compound of a kind of one kettle way.
Background technology
Benzazole compounds is widespread in nature, and contains substituent indoles on many phenyl ring and all has biological activity, and indoles and derivative thereof or a kind of important industrial chemicals are widely used in the various fields such as medicine, agricultural chemicals, dyestuff, food and spices.Melatonin has another name called brain platinum, is mainly produced by the 5-methoxy-Indole, and it directly acts on hypothalamus, has the sleep of promotion, endocrine regulation, the multiple physiological action such as strengthening immunity.Indomethacin can be in the situation of the fibrous synovial cell of the one-tenth that does not affect the rheumatoid arthritis people (FLS) growth, by mRNA, the protein expression two performance anti-inflammatory actions that suppress the cytokines such as IL-6 among the FLS.Isolated indoles alkaloid 5 from marine natural product, 6-two bromo-N, N-Dimethyltryptamine then shows significantly antidepressant effect.
Benzazole compounds is widely used, and is closely related with people's life.But because production cost is high, the market value height is not lower, therefore the research of synthesis of indole is very important, in recent years, it is gentle that people are seeking reaction conditions always, effectively, method Fischer method (the Nagasaka T. of easy synthetic this compounds, 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
3Be catalyzer, make the phenylhydrazone of aldehyde that the 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 of aniline (Tsutomu S., et al.J.Org.Chem.1979,44 (4): 578-582) take aniline as raw material, at AlCl
3Catalysis under, with BCl
3And ClCH
2The CN reaction, one of middle experience contains B
+The ring-type transition state, acidifying gets 2-amino-α-chloracetyl benzene, then uses NaBH in dioxane
4Reduce to get benzazolyl compounds, although the method step is simple, yield is on the low side; Organotin reagent is widely used in being connected thiazolinyl to aromatic ring with the palladium catalytic crosslinking reaction of various electrophilic reagents, is the synthetic comparatively desirable method of substituted indole, and the method uses organo-metallic as catalyzer, such 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 not high problem of ubiquity yield, and raw material and catalyzer that the method that has adopts are expensive, are difficult for realizing industrialization.
Summary of the invention
The object of the invention is to provide the method for the synthetic substituent indole compound of a kind of one kettle way.
The technical solution used in the present invention is for achieving the above object:
The method of the synthetic substituent indole compound of a kind of one kettle way, with Ortho Nitro Toluene derivative and N, dinethylformamide dimethylacetal or triethyl orthoformate are raw material, under alkaline oxygen free condition, in organic solvent, react, add then that reductive agent reduces, cyclization, namely obtain indole derivatives
Wherein, R is positioned at 4,5,6,7 singly replacement or polysubstituted; The R substituting group 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, in organic solvent, react 4-22h with 50-150 ℃, add then that reductive agent reduces at 25-60 ℃, 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 adding reductive agent reduces at 40-50 ℃, cyclization 1-2h obtains indole derivatives.
Described reduction, cyclization products therefrom are by extraction, and the method for recrystallization is separated, purifying.The solvent that uses in the described recrystallization purifying method is the mixed solvent of polar solvent and non-polar solvent.
Described alkali is a kind of in tetramethyleneimine, hexahydropyridine, piperazine, morpholine, quadrol or the triethylamine.
Described organic solvent is DMF, toluene, benzene, a trimethylbenzene, tetrahydrofuran (THF), Isosorbide-5-Nitrae-dioxane, a kind of in condensed ethandiol dme or the morpholine.
Described former dose is Raney's nickel and hydrazine, palladium carbon hydrogenation, tin protochloride, V-Brite B, iron-acetic acid or titanous chloride.The molar ratio of described reductive agent and Ortho Nitro Toluene derivative is 1-5:1.
Beneficial effect of the present invention:
1. the present invention is that usefulness " one kettle way " reaction is raw material by Ortho Nitro Toluene compounds conventional, that be easy to get directly, need not to separate, be purified into intermediate, by effective control reaction conditions, order of addition(of ingredients) and ratio, in same reaction vessel, directly add reductive agent, reduction, cyclisation obtain the derivative of indoles, one pot reaction synthesis of indole derivative.
2. the present invention adopts " one kettle way ", need not separation of intermediates, thereby has simplified the technological operation flow process; Shortened the reaction times; Save cost, improved the whole 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 synthetic of multiple substituent indole derivatives.
Embodiment
The following examples will better illustrate the present invention, but what need emphasize is to the invention is not restricted to the represented content of embodiment.
The method of synthetic substituent indole compound is to replace Ortho Nitro Toluene and N, dinethylformamide dimethylacetal or triethyl orthoformate are raw material, under alkaline oxygen free condition, in organic solvent, react, the intermediate that generates is without separation, and direct reducer reduces, cyclization obtains indole derivatives.Wherein reaction formula is:
R can be positioned at 4,5,6,7 in the formula, and R can be a kind of in hydrogen, alkyl or substituted hydrocarbon radical, alkoxyl group, amino, the halogen atom, can be a substituting group or a plurality of substituting group.Also original reagent all adopts the mode sample introduction that drips slowly;
Embodiment 1
Compd A: in the 100ml there-necked flask, add trimethylbenzene between 50ml; raw material 1(4-Chloro-2-Nitrobenzene, lower same) (0.69g, 4mmol); N; dinethylformamide dimethylacetal (0.95g, 8mmol), tetramethyleneimine (1.14g; 16mmol); nitrogen protection is fully stirred, and substrate is dissolved fully.Be warming up to 145 ℃, condensing reflux, reaction process TLC follows the tracks of, and disappears cool to room temperature until thin-layer chromatography shows raw material point.The palladium carbon that adds subsequently catalytic amount (20mg), and pass into hydrogen (10ml/min), the control temperature of reaction is at 45-50 ℃, react and be cooled to room temperature after 2 hours, suction filtration, filter residue extract with dichloromethane rinse several times, recrystallization (hexanaphthene: methylene dichloride: methyl alcohol=2:1:8(v/v)) obtains off-white color solid, yield 92.3%.
The preparation method of compd B-H is with compound A, its feed ratio is identical with compound 1, can obtain respectively compd B (productive rate 80.1%), 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: in the 100ml there-necked flask, add 50ml DMF (DMF), raw material 1(0.69g, 4mmol); DMF dimethylacetal (0.95g, 8mmol), tetramethyleneimine (1.14g; 16mmol), nitrogen protection is fully stirred, and substrate is dissolved fully.Be warming up to 130 ℃, condensing reflux, reaction process TLC follows the tracks of, and disappears cool to room temperature until thin-layer chromatography shows raw material point.The Raney's nickel that adds subsequently catalytic amount (100mg), slowly splash into 85% hydrazine hydrate (0.35g with dropping funnel, 6mmol), be warming up to 30 ℃, added the hydrazine hydrate of same amount every 30 minutes, the control temperature of reaction is at 45-50 ℃, TLC follows the tracks of, disappear until thin-layer chromatography shows the component point of intermediate product, be cooled to room temperature, catalyzer is removed (can not drain in case the catalyzer spontaneous combustion) with diatomite filtration.Filter residue with dichloromethane rinse several times, extraction, (hexanaphthene: methylene dichloride: methyl alcohol=2:1:8) obtains off-white color solid, yield 88.1% to recrystallization.
Replace raw material 1 with raw material 2-14, its feed ratio is identical with compound 1, can obtain respectively compd B (productive rate 90.1%), 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: in the 100ml there-necked flask, add 50ml tetrahydrofuran (THF) (THF), raw material 1(0.69g, 4mmol), N; dinethylformamide dimethylacetal (0.95g, 8mmol), tetramethyleneimine (1.14g, 16mmol); nitrogen protection is fully stirred, and substrate is dissolved fully.Be warming up to 80 ℃, condensing reflux, reaction process is followed the tracks of with TLC, disappears cool to room temperature until thin-layer chromatography shows raw material point.Add subsequently ferrous acetate (1.4g, 8mmol), the control temperature of reaction is at 45-50 ℃, and TLC follows the tracks of, and disappears until thin-layer chromatography shows the component point of intermediate product, be cooled to room temperature, suction filtration, filter residue extract with dichloromethane rinse several times, (hexanaphthene: methylene dichloride: methyl alcohol=2:1:8) obtains off-white color solid, yield 78.5% to recrystallization.
Replace raw material 1 with raw material 2-14, its feed ratio is identical with compound 1, can obtain respectively compd B (productive rate 77.5%), 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: in the 100ml there-necked flask, add 50ml condensed ethandiol dme, raw material 1(0.69g, 4mmol), N; dinethylformamide dimethylacetal (0.95g, 8mmol), piperazine (1.03g, 12mmol); nitrogen protection is fully stirred, and substrate is dissolved fully.Be warming up to 135 ℃, condensing reflux, reaction process is followed the tracks of with TLC, disappears cool to room temperature until thin-layer chromatography shows raw material point.Add subsequently tin protochloride (1.8g, 8mmol), the control temperature of reaction is at 45-50 ℃, and TLC follows the tracks of, and disappears until thin-layer chromatography shows the component point of intermediate product, be cooled to room temperature, suction filtration, filter residue extract with dichloromethane rinse several times, (hexanaphthene: methylene dichloride: methyl alcohol=2:1:8) obtains off-white color solid, yield 90.3% to recrystallization.
Replace raw material 1 with raw material 2-14, its feed ratio is identical with compound 1, can obtain respectively compd B (productive rate 92.1%), 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 of adding 50ml in the 100ml there-necked flask (toluene: dioxane=3:1); raw material 1(0.69g; 4mmol), DMF dimethylacetal (0.95g; 8mmol); piperazine (1.03g, 12mmol), nitrogen protection; fully stir, substrate is dissolved fully.Be warming up to 101 ℃, logical condensate return is used the TLC tracking reaction process, disappears cool to room temperature until thin-layer chromatography shows raw material point.Add subsequently V-Brite B (1.4g, 8mmol), the control temperature of reaction is at 45-50 ℃, and TLC follows the tracks of, and disappears until thin-layer chromatography shows intermediate product component point, be cooled to room temperature, suction filtration, filter residue extract with dichloromethane rinse several times, (hexanaphthene: methylene dichloride: methyl alcohol=2:1:8) obtains off-white color solid, yield 85.4% to recrystallization.
Replace raw material 1 with raw material 2-14, its feed ratio is identical with compound 1, can obtain respectively compd B (productive rate 87.1%), 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: in the 100ml there-necked flask, add 50ml morpholine, raw material 1(0.69g, 4mmol), DMF dimethylacetal (0.95g, 8mmol), nitrogen protection is fully stirred, and substrate is dissolved fully.Be warming up to 120 ℃, logical condensate return, reaction process is followed the tracks of with TLC, disappears cool to room temperature until thin-layer chromatography shows raw material point.Add subsequently titanous chloride (1.2g, 8mmol), the control temperature of reaction is at 45-50 ℃, and TLC follows the tracks of, and disappears until thin-layer chromatography shows intermediate product component point, be cooled to room temperature, suction filtration, filter residue extract with dichloromethane rinse several times, (hexanaphthene: methylene dichloride: methyl alcohol=2:1:8) obtains off-white color solid, yield 92.1% to recrystallization.
Replace raw material 1 with raw material 2-14, its feed ratio is identical with compound 1, can obtain respectively compd B (productive rate 91.3%), 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: in the 100ml there-necked flask, add trimethylbenzene between 50ml, raw material 1(0.69g, 4mmol), triethyl orthoformate (0.60g, 4mmol), tetramethyleneimine (1.14g, 16mmol), nitrogen protection is fully stirred, and substrate is dissolved fully.Be warming up to 145 ℃, logical condensate return, reaction process is followed the tracks of with TLC, disappears cool to room temperature until thin-layer chromatography shows raw material point.The palladium carbon that adds subsequently catalytic amount (50mg), and pass into hydrogen (10ml/min), the control temperature of reaction is at 45-50 ℃, react and be cooled to room temperature after 2 hours, suction filtration, filter residue extract with dichloromethane rinse several times, (hexanaphthene: methylene dichloride: methyl alcohol=2:1:8) obtains off-white color solid, yield 87.3% to recrystallization.
Replace raw material 1 with raw material 2-14, its feed ratio is identical with compound 1, can obtain respectively compd B (productive rate 82.3%), 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: in the 100ml there-necked flask, add 50ml DMF (DMF), raw material 1(0.69g, 4mmol); triethyl orthoformate (0.60g, 4mmol), pyridine (1.27g, 16mmol); nitrogen protection is fully stirred, and substrate is dissolved fully.Be warming up to 130 ℃, logical condensate return, reaction process is followed the tracks of with TLC, disappears cool to room temperature until thin-layer chromatography shows raw material point.The Raney's nickel that adds subsequently catalytic amount (100mg), slowly splash into 85% hydrazine hydrate (0.35g with dropping funnel, 6mmol), be warming up to 30 ℃, added the hydrazine hydrate of same amount every 30 minutes, the control temperature of reaction is at 45-50 ℃, TLC follows the tracks of, disappear until thin-layer chromatography shows intermediate product component point, be cooled to room temperature, catalyzer is removed (can not drain in case the catalyzer spontaneous combustion) with diatomite filtration.Filter residue with dichloromethane rinse several times, extraction, (hexanaphthene: methylene dichloride: methyl alcohol=2:1:8) obtains off-white color solid, yield 90.2% to recrystallization.
Replace raw material 1 with raw material 2-14, its feed ratio is identical with compound 1, can obtain respectively compd B (productive rate 80.1%), 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: in the 100ml there-necked flask, add 50ml tetrahydrofuran (THF) (THF), raw material 1(0.69g, 4mmol), triethyl orthoformate (0.60g, 4mmol), triethylamine (1.62g, 16mmol), nitrogen protection is fully stirred, and substrate is dissolved fully.Be warming up to 80 ℃, logical condensate return, reaction process is followed the tracks of with TLC, disappears cool to room temperature until thin-layer chromatography shows raw material point.Add subsequently ferrous acetate (1.4g, 8mmol), the control temperature of reaction is at 45-50 ℃, and TLC follows the tracks of, and disappears until thin-layer chromatography shows intermediate product component point, be cooled to room temperature, suction filtration, filter residue extract with dichloromethane rinse several times, (hexanaphthene: methylene dichloride: methyl alcohol=2:1:8) obtains off-white color solid, yield 82.4% to recrystallization.
Replace raw material 1 with raw material 2-14, its feed ratio is identical with compound 1, can obtain respectively compd B (productive rate 79.1%), 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: in the 100ml there-necked flask, add 50ml morpholine, raw material 1(0.69g, 4mmol), triethyl orthoformate (0.60g, 4mmol), nitrogen protection is fully stirred, and substrate is dissolved fully.Be warming up to 120 ℃, logical condensate return, reaction process is followed the tracks of with TLC, disappears cool to room temperature until thin-layer chromatography shows raw material point.The Raney's nickel that adds subsequently catalytic amount (100mg), slowly splash into 85% hydrazine hydrate (0.35g with dropping funnel, 6mmol), be warming up to 30 ℃, added the hydrazine hydrate of same amount every 30 minutes, the control temperature of reaction is at 45-50 ℃, TLC follows the tracks of, disappear until thin-layer chromatography shows intermediate product component point, be cooled to room temperature, catalyzer is removed (can not drain in case the catalyzer spontaneous combustion) with diatomite filtration.Filter residue with dichloromethane rinse several times, extraction, (hexanaphthene: methylene dichloride: methyl alcohol=2:1:8) obtains off-white color solid, yield 86.1% to recrystallization.
Replace raw material 1 with raw material 2-14, its feed ratio is identical with compound 1, can obtain respectively compd B (productive rate 87.2%), 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 (9)
1. the method for the synthetic substituent indole compound of an one kettle way, it is characterized in that: with Ortho Nitro Toluene derivative and N, dinethylformamide dimethylacetal or triethyl orthoformate are raw material, under alkaline oxygen free condition, in organic solvent, react, add then that reductive agent reduces, cyclization, namely obtain indole derivatives
Wherein, R is positioned at 4,5,6,7 singly replacement or polysubstituted; The R substituting group is hydrogen, alkyl, substituted hydrocarbon radical, alkoxyl group, amino or halogen atom.
2. by the method for the synthetic substituent indole compound of one kettle way claimed in claim 1, it is characterized in that: the reaction formula of described synthetic method is:
3. the method for synthesizing substituent indole compound by claim 1 or 2 described one kettle ways, it is characterized in that: described with Ortho Nitro Toluene derivative and N, dinethylformamide dimethylacetal or triethyl orthoformate are raw material, under alkaline oxygen free condition, in organic solvent, react 4-22h with 50-150 ℃, add then that reductive agent reduces at 25-60 ℃, 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.
4. by the method for the synthetic substituent indole compound of one kettle way claimed in claim 3, it is characterized in that: described adding reductive agent reduces at 40-50 ℃, cyclization 1-2h obtains indole derivatives.
5. by the method for the synthetic substituent indole compound of one kettle way claimed in claim 1, it is characterized in that: described reduction, cyclization products therefrom are by extraction, and the method for recrystallization is separated, purifying.
6. by the method for the synthetic substituent indole compound of one kettle way claimed in claim 1, it is characterized in that: described alkali is a kind of in tetramethyleneimine, hexahydropyridine, piperazine, morpholine, quadrol or the triethylamine.
7. the method for synthesizing substituent indole compound by one kettle way claimed in claim 1, it is characterized in that: described organic solvent is N, dinethylformamide, toluene, benzene, a trimethylbenzene, tetrahydrofuran (THF), Isosorbide-5-Nitrae-dioxane, a kind of in condensed ethandiol dme or the morpholine.
8. by the method for the synthetic substituent indole compound of one kettle way claimed in claim 1, it is characterized in that: described former dose is Raney's nickel and hydrazine, palladium carbon hydrogenation, tin protochloride, V-Brite B, iron-acetic acid or titanous chloride.
9. by the method for the synthetic substituent indole compound of one kettle way claimed in claim 1, it is characterized in that: the molar ratio of described reductive agent and Ortho Nitro Toluene derivative is 1-5:1.
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| CN110551055A (en) * | 2018-06-02 | 2019-12-10 | 新发药业有限公司 | Preparation method of 3- (4-chlorobutyl) -5-cyanoindole |
| CN112457235A (en) * | 2020-12-02 | 2021-03-09 | 烟台凯博医药科技有限公司 | Preparation method of 7-methylindole |
| CN113181850A (en) * | 2021-04-23 | 2021-07-30 | 上海应用技术大学 | Microchannel preparation method of indole compound |
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| CN112457235A (en) * | 2020-12-02 | 2021-03-09 | 烟台凯博医药科技有限公司 | Preparation method of 7-methylindole |
| CN112457235B (en) * | 2020-12-02 | 2023-04-25 | 烟台凯博医药科技有限公司 | Preparation method of 7-methylindole |
| CN113181850A (en) * | 2021-04-23 | 2021-07-30 | 上海应用技术大学 | Microchannel preparation method of indole compound |
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