CN113666860A - Preparation method of 7-ethyl tryptophol - Google Patents

Preparation method of 7-ethyl tryptophol Download PDF

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CN113666860A
CN113666860A CN202010411678.4A CN202010411678A CN113666860A CN 113666860 A CN113666860 A CN 113666860A CN 202010411678 A CN202010411678 A CN 202010411678A CN 113666860 A CN113666860 A CN 113666860A
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CN113666860B (en
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王亚青
鲍广龙
刘忠
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Lunan Pharmaceutical Group Corp
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/12—Radicals substituted by oxygen atoms
    • 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
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    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
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    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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Abstract

The invention belongs to the technical field of drug synthesis, and particularly relates to a preparation method of 7-ethyl tryptophol, which takes 7-ethyl indole as a raw material to react with ethylene carbonate under the action of alkali to synthesize the 7-ethyl tryptophol; according to the method, the ethylene carbonate reagent product of hydroxyethyl is introduced as carbon dioxide, so that the method is clean, environment-friendly, convenient to post-treat, capable of avoiding using dangerous chemical reagents, mild in reaction, economic, environment-friendly, high in yield and suitable for industrial production.

Description

Preparation method of 7-ethyl tryptophol
Technical Field
The invention belongs to the technical field of drug synthesis, and particularly relates to a preparation method of 7-ethyl tryptophol.
Background
Etodolac (Etodolac) is a powerful non-steroidal anti-inflammatory analgesic, is used for treating rheumatic arthritis, rheumatoid arthritis, osteoarthritis and other symptoms, has the characteristics of good tolerance, light toxic and side effects, strong analgesic effect and the like, has few gastrointestinal adverse reactions, and is particularly suitable for old patients. The drug is developed by AHP Wyeth-Ayesrt company in the United states, is firstly marketed in the United kingdom in 1985, and has the following chemical structural formula:
Figure BDA0002490828010000011
the 7-ethyl tryptophol is used as a key intermediate for synthesizing the etodolac, directly influences the production, market supply and quality problems of the drug, and has the following chemical structural formula:
Figure BDA0002490828010000012
the preparation methods reported at present for 7-ethyl tryptophol mainly comprise the following methods:
U.S. Pat. No.3, 4062869A, 2006166947A1 and document 7-Ethyl-1H-indole Synthesis, Jiangsu chemical engineering, 1993,21(1),17-19 and 7-Ethyl indole Synthesis, Chinese journal of pharmaceutical chemistry 1997,7(1),57-59, Heterocycles,2018,96(1),67-73 report that o-nitroethylbenzene, a by-product of p-nitroethylbenzene, an industrially produced chloramphenicol intermediate, or its downstream intermediate, is used as a raw material, reduced with tin powder/hydrochloric acid to obtain o-ethylaniline, then forms oximidoacetamide derivatives with chloral hydrate and hydroxylamine hydrochloride under acidic conditions, cyclizes in concentrated sulfuric acid to obtain 7-Ethylindolinone, then reduces with lithium aluminum hydride to obtain 7-Ethyl indole, finally reacts with oxalyl chloride, and is prepared by esterification and sodium borohydride reduction:
Figure BDA0002490828010000013
however, the above process has the disadvantages of long synthetic route, inconvenient operation, low overall yield, high risk of the reducing agent, high price and unsuitability for industrial production.
U.S. Pat. No. 5, 4585877A and the literature, "research on Etodolac Synthesis Process", Tianjin chemical industry, 2004,18(5),22-23, Etodolac Synthesis Process ", Proc. 2005,56(8), 1536-Bu 1540 also uses o-nitroethylbenzene as raw material, and obtains o-ethylaniline by iron powder reduction, and then obtains o-ethylanilide hydrochloride by diazotization reaction, reduction with sodium sulfite (sodium bisulfite or stannous chloride), and then reflux reaction with 2, 3-dihydrofuran in 1, 4-dioxane:
Figure BDA0002490828010000021
the Fischer Indole synthesis method is a mainstream process for producing 7-ethyl tryptophol at present, and is the simplest synthesis method with the lowest production cost in the current process. The Fischer Indole synthesis seems to be a cleaner synthesis only from the reaction formula, but the method is not actually used for synthesizing 7-ethyl tryptophol, and on one hand, the technology needs a large amount of environmentally-friendly organic solvents such as acetonitrile, DMF, DMAc, isobutanol and the like or expensive solvents, and the solvent recovery rate is low; on the other hand, strong acid is required for catalyzing the Fischer rearrangement reaction to form the indole ring, but the strong acid can also catalyze the indole ring to generate chain reaction to generate purple-black sticky polymers, so that a plurality of impurities are generated, the purity of a crude product is low, the post-treatment is complex, and the product 7-ethyl tryptophol obtained through reaction separation is a dark-colored (usually brown-black) sticky jelly or oily substance. The separation and purification of such a low-purity dark gum has been reported to be a silica gel column separation method (see U.S. Pat. Nos. 4585877 and WO9959970) and an extraction separation method (see W02005002523), and the like. Although the silica gel column separation method can obtain the product 7-ethyl tryptophol with high purity, the use of a large amount of solvent is not economical and is not practical in industrial production. Although the extraction separation method is an effective method for improving the purity of the industrial 7-ethyl tryptophol at present, the purity of the 7-ethyl tryptophol crude product (the content is usually 60-85%) is still only 95-97% after separation and purification, and the color of the product is dark brown (see W02005002523), which is still unsatisfactory.
In addition, after indole cyclization, the system contains unreacted aldehyde (obtained by hydrolyzing 2, 3-dihydrofuran) and 2, 3-dihydrofuran, and the following three byproducts are easily generated, so that the crude product has low purity and complex post-treatment:
Figure BDA0002490828010000022
in addition, the 2, 3-dihydrofuran with higher price is used in the process, so that the production cost is correspondingly increased.
The chinese patent applications CN1740153A, CN1740154A and the document "new synthesis process of 7-ethyl tryptophol", the college of chemical engineering, the report of 2010,24(1), 127-:
Figure BDA0002490828010000031
however, the above process still has difficulty in avoiding the disadvantages of the Fischer Indole synthesis and the use of the more expensive 2, 3-dihydrofuran.
Similarly, Chinese patent application CN107522649A and the literature Chemical Engineering & Processing, Process Intensification,121(2017)144-148 adopt a tubular continuous flow reaction technology adopting microwave heating to react phenylhydrazine hydrochloride with 4-hydroxybutyraldehyde, thereby realizing the continuous synthesis reaction of 7-ethyl tryptophol. Although the use of strong acid in the Fischer Indole synthesis method is avoided theoretically, the process has limited batch quantity and is not suitable for industrial scale-up production.
The document Heterocycles,2003,60(5)1095-1110 uses 3-ethoxytetrahydrofuran, which is an active precursor of 2, 3-dihydrofuran, as a donor of 4-hydroxybutyraldehyde, and also cannot avoid the problem of high production cost:
Figure BDA0002490828010000032
the Journal of laboratory Compounds and Radiopharmaceuticals, Vol.XIV, No.3,1978,411-425, modified the strategy to prepare the compound by hydrolytic reduction after introduction of a cyano group into a 3-substituted-7-ethylindole:
Figure BDA0002490828010000033
however, the process applies the highly toxic KCN, so that the operation risk is high, the obtained cyano-substituted intermediate has 2-bit isomer impurities, the purity of the obtained product is low, and in addition, the carboxylic acid reduction uses lithium aluminum hydride with high price and high risk, so that the operation safety is low, and the industrial scale-up production is difficult.
Furthermore, the Journal of Medicinal Chemistry,1976,19(3),391-395 of the literature has been designed and synthesized for the related indolinone derivatives by the Reformatsky reaction, but this process also requires the use of relatively expensive and dangerous lithium aluminum hydride:
Figure BDA0002490828010000034
in addition, the documents Organic Syntheses, col. Vol.9, p.417 (1998); vol.74, p.248(1997) firstly uses tert-butyldimethylsilyl chloride (TMDMSCl) to protect 1-position indole hydrogen under the condition of n-butyllithium, introduces bromine at 3-position through NBS, and then performs nucleophilic substitution with propylene oxide after Li substitution under the condition of n-butyllithium, and performs deprotection to obtain related derivatives:
Figure BDA0002490828010000041
however, the process has the advantages of more synthesis steps, more complicated operation and lower overall yield; meanwhile, the method needs to be applied to the hazardous reagent n-butyllithium which is in contact with water and carbon dioxide, is spontaneously combusted, is heated, is flammable in open fire and needs to be operated at ultralow temperature for many times, so that the operation safety is low, and the industrial scale-up production is difficult.
In summary, the reported preparation methods of 7-ethyl tryptophol mainly have the following problems:
1. the process route is longer, the final product relates to the vacuum fractionation operation, the operation is complicated, and the overall yield is lower.
2. The Fischer Indole synthesis method under strong acid condition is adopted to prepare the target product, and the obtained product has the problems of more impurities, difficult purification and lower yield.
3. The process needs a large amount of environmentally-friendly organic solvents such as acetonitrile, DMF, DMAc, isobutanol and the like or expensive solvents, and has the problem of low solvent recovery rate.
4. The process adopts lithium aluminum hydride with higher risk and KCN which is a highly toxic product, so that the operation safety is lower.
5. The problem of high production cost is caused by adopting slightly expensive 2, 3-dihydrofuran or an active precursor 3-ethoxy tetrahydrofuran thereof as a donor of 4-hydroxybutyraldehyde.
In summary, the existing preparation method of 7-ethyl tryptophol has many defects in the aspects of safe process, complex operation, low yield, high production cost and the like, so that the research and search of a reaction route which has mild reaction conditions, simple and convenient operation process, high product yield, high purity and low production cost and is suitable for industrial production of 7-ethyl tryptophol still needs to be solved at present.
Disclosure of Invention
Aiming at the problems of the existing 7-ethyl tryptophol preparation technology, the invention provides a novel preparation method of 7-ethyl tryptophol. The method has mild reaction conditions and simple and convenient operation process, and the prepared target product has higher purity and yield.
The specific technical scheme of the invention is as follows:
Figure BDA0002490828010000051
a preparation method of 7-ethyl tryptophol specifically comprises the following steps:
adding 7-ethyl indole and alkali into a reaction solvent at room temperature, adding ethylene carbonate at controlled temperature, controlling the temperature until the reaction is finished, and carrying out post-treatment to obtain the target product.
Preferably, the base is one or a combination of potassium carbonate, sodium bicarbonate, triethylamine, N, N-diisopropylethylamine and pyridine; among them, potassium carbonate is particularly preferable.
Preferably, the reaction solvent is one or a combination of benzene, toluene, xylene, N-dimethylformamide, 1, 4-dioxane, dimethyl sulfoxide and N-methylpyrrolidone, wherein N, N-dimethylformamide is particularly preferred.
Preferably, the feeding molar ratio of the 7-ethylindole to the alkali to the ethylene carbonate is 1: 1.0-2.0: 1.5 to 3.0, preferably 1: 1.2: 2.2.
in a preferable scheme, the temperature for adding the ethylene carbonate at the controlled temperature is 0-30 ℃; the reaction temperature is 90-120 ℃.
Preferably, the post-treatment step is as follows: cooling the reaction liquid to room temperature, filtering, adding dichloromethane into the filtrate to extract and separate an organic phase, washing the organic phase with saturated saline solution, drying with anhydrous sodium sulfate, filtering, and concentrating the filtrate under reduced pressure until the filtrate is dried to obtain the target product.
The invention has the beneficial effects that:
1. the invention provides a novel preparation method of 7-ethyl tryptophol, which is prepared by taking 7-ethyl Indole as a starting material and reacting with ethylene carbonate under an alkaline condition, thereby not only avoiding the problem of higher production cost caused by adopting 2, 3-dihydrofuran or an active precursor thereof, namely 3-ethoxy tetrahydrofuran, as a donor of 4-hydroxybutyraldehyde, but also avoiding the problems of more impurities, difficult purification and lower yield of a Fischer Indole synthesis method for preparing a target product;
2. meanwhile, the use of lithium aluminum hydride with higher risk and a highly toxic KCN is effectively avoided, the operation safety is improved, and the target product is not required to be purified by reduced pressure fractionation operation, so that the production operation is simplified;
3. the ethylene carbonate reagent product introduced with hydroxyethyl is carbon dioxide, so that the method is clean and environment-friendly and is convenient for post-treatment;
4. compared with the prior art, the preparation process of the 7-ethyl tryptophol has the advantages of shortened process route, simple and safe operation and suitability for industrial production.
Detailed Description
The invention is further illustrated by the following examples, which should be properly understood: the examples of the present invention are merely illustrative and not restrictive, and therefore, the present invention may be modified in a simple manner without departing from the scope of the invention as claimed.
The structure of the 7-ethyl tryptophol compound obtained by the invention is confirmed as follows:
Figure BDA0002490828010000061
ESI-HRMS(m/z)：190.1234[M+H]+；1H NMR(400MHz,CDCl3)δ8.05(br s,1H),7.50(d,J＝8.0Hz,1H),7.15-7.07(m,3H),3.92(t,J＝6.5Hz,2H),3.05(t,J＝6.0Hz,2H),2.87(q,J1＝8.0Hz,J2＝15.5Hz,J3＝23.0Hz,2H)，1.38(t,J＝7.8Hz,3H)；13C NMR(100MHz,CDCl3)δ136.05,127.83,126.16,122.02,119.94,119.30,116.06,112.40,62.34,29.58,24.40,13.63.
in the following examples, various procedures and methods not described in detail are conventional methods well known in the art.
Example 1
Adding 7-ethyl indole (14.52g, 0.1mol) and potassium carbonate (16.58g, 0.12mol) into N, N-dimethylformamide (150ml) at room temperature, controlling the temperature to be 10-15 ℃, adding ethylene carbonate (19.37g, 0.22mol), controlling the temperature to be 110-115 ℃ after the reaction is finished, cooling the reaction liquid to room temperature, filtering, adding dichloromethane (100ml) into filtrate, separating liquid to obtain an organic phase, washing the organic phase by saturated saline (100ml multiplied by 2), drying by anhydrous sodium sulfate, filtering, concentrating the filtrate under reduced pressure until the organic phase is dry to obtain the target product, wherein the yield is 98.7%, and the HPLC purity is 99.92%.
Example 2
Adding 7-ethylindole (14.52g, 0.1mol) and potassium carbonate (13.82g, 0.1mol) into 1.4-dioxane (150ml) at room temperature, controlling the temperature to be 0-5 ℃, adding ethylene carbonate (19.37g, 0.22mol), controlling the temperature to be 90-100 ℃ after the addition is finished, cooling the reaction liquid to room temperature, filtering, adding dichloromethane (100ml) into filtrate, separating liquid to obtain an organic phase, washing the organic phase by saturated saline (100ml multiplied by 2), drying by anhydrous sodium sulfate, filtering, concentrating the filtrate under reduced pressure until the organic phase is dry to obtain the target product, wherein the yield is 94.6%, and the HPLC purity is 99.86%.
Example 3
Adding 7-ethyl indole (14.52g, 0.1mol) and potassium carbonate (27.64g, 0.2mol) into xylene (150ml) at room temperature, controlling the temperature to be 25-30 ℃, adding ethylene carbonate (19.37g, 0.22mol), controlling the temperature to be 115-120 ℃ after the addition is finished, cooling the reaction liquid to room temperature, filtering, adding dichloromethane (100ml) into the filtrate, separating liquid to obtain an organic phase, washing the organic phase by saturated saline (100ml multiplied by 2), drying by anhydrous sodium sulfate, filtering, concentrating the filtrate under reduced pressure until the filtrate is dry to obtain the target product, wherein the yield is 93.9%, and the HPLC purity is 99.76%.
Example 4
Adding 7-ethyl indole (14.52g, 0.1mol) and potassium carbonate (34.56g, 0.25mol) into toluene (150ml) at room temperature, controlling the temperature to be-5-0 ℃, adding ethylene carbonate (19.37g, 0.22mol), controlling the temperature to be 85-90 ℃ after the addition is finished, cooling the reaction liquid to room temperature, filtering, adding dichloromethane (100ml) into the filtrate, separating liquid to obtain an organic phase, washing the organic phase by saturated saline (100ml multiplied by 2), drying by anhydrous sodium sulfate, filtering, concentrating the filtrate under reduced pressure until the organic phase is dry to obtain the target product, wherein the yield is 86.9%, and the HPLC purity is 99.65%.
Example 5
Adding 7-ethyl indole (14.52g, 0.1mol) and sodium bicarbonate (10.08g, 0.12mol) into p-xylene (150ml) at room temperature, controlling the temperature to be 10-15 ℃, adding ethylene carbonate (13.21g, 0.15mol), controlling the temperature to be 110-115 ℃ after the addition is finished, cooling the reaction liquid to room temperature, filtering, adding dichloromethane (100ml) into the filtrate, separating liquid to obtain an organic phase, washing the organic phase by saturated saline (100ml multiplied by 2), drying by anhydrous sodium sulfate, filtering, concentrating the filtrate under reduced pressure until the organic phase is dry to obtain the target product, wherein the yield is 95.5%, and the HPLC purity is 99.88%.
Example 6
Adding 7-ethyl indole (14.52g, 0.1mol) and triethylamine (12.14g, 0.12mol) into dimethyl sulfoxide (150ml) at room temperature, controlling the temperature to be 10-15 ℃, adding ethylene carbonate (26.42g, 0.3mol), controlling the temperature to be 110-115 ℃ after the addition is finished, cooling the reaction liquid to room temperature, filtering, adding dichloromethane (100ml) into the filtrate, separating liquid to obtain an organic phase, washing the organic phase by saturated saline (100ml multiplied by 2), drying by anhydrous sodium sulfate, filtering, concentrating the filtrate under reduced pressure until the organic phase is dry to obtain the target product, wherein the yield is 93.7%, and the HPLC purity is 99.78%.
Example 7
Adding 7-ethylindole (14.52g, 0.1mol) and N, N-diisopropylethylamine (15.51g, 0.12mol) into N-methylpyrrolidone (150ml) at room temperature, controlling the temperature to be 10-15 ℃, adding ethylene carbonate (8.81g, 0.1mol), controlling the temperature to be 110-115 ℃ after the reaction is finished, cooling the reaction liquid to room temperature, filtering, adding dichloromethane (100ml) into the filtrate, separating the filtrate to obtain an organic phase, washing the organic phase by saturated saline (100ml multiplied by 2), drying by anhydrous sodium sulfate, filtering, concentrating the filtrate under reduced pressure to be dry to obtain the target product, wherein the yield is 86.6%, and the HPLC purity is 99.66%.
Example 8
Adding 7-ethyl indole (14.52g, 0.1mol) and pyridine (9.50g, 0.12mol) into N-methylpyrrolidone (150ml) at room temperature, adding ethylene carbonate (30.82g, 0.35mol) at the temperature of 10-15 ℃, controlling the temperature to be 120-125 ℃ after the addition is finished, cooling the reaction liquid to room temperature, filtering, adding dichloromethane (100ml) into the filtrate, separating liquid to obtain an organic phase, washing the organic phase by saturated saline (100ml multiplied by 2), drying by anhydrous sodium sulfate, filtering, concentrating the filtrate under reduced pressure until the organic phase is dry to obtain the target product, wherein the yield is 85.2%, and the HPLC purity is 99.64%.

Claims (7)

1. A preparation method of 7-ethyl tryptophol is characterized in that 7-ethyl indole reacts with ethylene carbonate under the action of alkali to obtain the 7-ethyl tryptophol, and the synthetic route is as follows:
Figure FDA0002490826000000011
2. the method of claim 1, comprising the steps of: adding 7-ethyl indole and alkali into a reaction solvent at room temperature, adding ethylene carbonate at controlled temperature, controlling the temperature until the reaction is finished, and carrying out post-treatment to obtain the target product.
3. The method according to claim 2, wherein the base is selected from potassium carbonate, sodium bicarbonate, triethylamine, N, N-diisopropylethylamine, pyridine, or a combination thereof.
4. The preparation method according to claim 2, wherein the feeding molar ratio of the 7-ethylindole to the base and the ethylene carbonate is 1: 1.0-2.0: 1.5 to 3.0.
5. The method according to claim 2, wherein the reaction solvent is one or a combination of benzene, toluene, xylene, N-dimethylformamide, 1, 4-dioxane, dimethyl sulfoxide and N-methylpyrrolidone.
6. The method according to claim 2, wherein the temperature of the ethylene carbonate is 0 to 30 ℃.
7. The preparation method according to claim 2, wherein the reaction temperature is 90-120 ℃.
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115650898A (en) * 2022-09-13 2023-01-31 华南理工大学 Synthesis method of 2-substituted 7-methoxy-tryptophol derivative

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1740153A (en) * 2005-08-23 2006-03-01 杭州科本化工有限公司 Prepn process of 7-ethyl tryptophol
CN1740154A (en) * 2005-08-23 2006-03-01 杭州科本化工有限公司 Prepn process of 7-ethyl tryptophol
CN105829288A (en) * 2013-12-19 2016-08-03 埃科特莱茵药品有限公司 Antibacterial 1h-indazole and 1h-indole derivatives
CN107522649A (en) * 2017-08-08 2017-12-29 衢州学院 A kind of 7 ethyl tryptophol method for continuously synthesizing of microwave assisted
KR20190081250A (en) * 2017-12-29 2019-07-09 아크로마코리아 주식회사 The preparing method of disperse orange dye

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1740153A (en) * 2005-08-23 2006-03-01 杭州科本化工有限公司 Prepn process of 7-ethyl tryptophol
CN1740154A (en) * 2005-08-23 2006-03-01 杭州科本化工有限公司 Prepn process of 7-ethyl tryptophol
CN105829288A (en) * 2013-12-19 2016-08-03 埃科特莱茵药品有限公司 Antibacterial 1h-indazole and 1h-indole derivatives
CN107522649A (en) * 2017-08-08 2017-12-29 衢州学院 A kind of 7 ethyl tryptophol method for continuously synthesizing of microwave assisted
KR20190081250A (en) * 2017-12-29 2019-07-09 아크로마코리아 주식회사 The preparing method of disperse orange dye

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
GAO GUOHUA，等: "Hydroxyalkylation of indole with cyclic carbonates catalyzed by ionic liquids", 《CHINESE JOURNAL OF CATALYSIS》, vol. 34, no. 6, pages 1187 - 1191 *
PAUL M WOOD，等: "Bicyclic derivatives of the potent dual aromatase-steroid sulfatase inhibitor 2-bromo-4- {[(4-cyanophenyl)(4h-1, 2, 4-triazol-4-yl)amino] methyl} phenylsulfamate: synthesis, SAR, crystal structure, and in vitro and in vivo activities", 《CHEMMEDCHEM》, vol. 5, no. 9, pages 1577 - 1593, XP055041821, DOI: 10.1002/cmdc.201000203 *
SIMON J. GARDEN，等: "A versatile synthetic methodology for the synthesis of tryptophols", 《TETRAHEDRON》, vol. 58, pages 8399 - 8412 *
吕延文，等: "7-乙基色醇的合成新工艺", 《高校化学工程学报》, vol. 24, no. 1, pages 127 - 131 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115650898A (en) * 2022-09-13 2023-01-31 华南理工大学 Synthesis method of 2-substituted 7-methoxy-tryptophol derivative

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