CN109384787B - Method for synthesizing hydrogenated pyridine spiro indoline ring under catalysis of monovalent silver - Google Patents
Method for synthesizing hydrogenated pyridine spiro indoline ring under catalysis of monovalent silver Download PDFInfo
- Publication number
- CN109384787B CN109384787B CN201710670364.4A CN201710670364A CN109384787B CN 109384787 B CN109384787 B CN 109384787B CN 201710670364 A CN201710670364 A CN 201710670364A CN 109384787 B CN109384787 B CN 109384787B
- Authority
- CN
- China
- Prior art keywords
- reaction
- silver
- reducing agent
- substituted
- hexane
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/10—Spiro-condensed systems
Abstract
The invention provides a synthesis method for generating a hydrogenated pyridine spiro indoline ring by using an indole-containing tryptamine alkyne amide substrate under the room temperature condition under the action of monovalent silver and a reducing agent, wherein the reaction general formula is as follows, and R in the formula1，R2，R3，R4As described in the claims and specification. The silver catalyst required by the reaction is one of silver trifluoromethanesulfonate, silver hexafluoroantimonate, silver tetrafluoroborate and silver bis (trifluoromethanesulfonyl) imide. The reducing agent required for the reaction is hans ester. The media required for the reaction are: toluene. The reaction is carried out by stirring at room temperature, and the method has the advantages of easily available raw materials, simple operation, wide application range, good atom economy, green reaction and low cost.
Description
Technical Field
The invention belongs to the technical field of medicines, and relates to a synthesis method of a hydrogenated pyridine spiro indoline ring, in particular to a synthesis method of a hydrogenated pyridine spiro indoline ring generated by a tryptamine alkyne amide substrate containing indole at room temperature under the action of monovalent silver and a reducing agent.
Background
Hydrogenated pyridine spiro indoline rings are a very important class of structures, which exist in natural products and active molecules of some indole alkaloids, (angelw.chem.int.ed., 2010,49,2000., j.med.chem.,2013,56,9275., angelw.chem.int.ed., 2013,52,10204.) in recent years, some active molecules containing such structures are continuously reported, and the search for a simple and effective synthetic method becomes particularly important for researching the structure-activity relationship thereof, so that the structures form the focus of attention of organic chemists and even pharmaceutical chemists. The methods currently reported for the synthesis of hydrogenated pyridine spiroindoline rings are:
1. intramolecular dearomatization and cyclization to obtain the hydrogenated pyridine spiro indoline ring. (Angew. chem. int.Ed.,2013,52,10204.)
The method is reported by Y.Takemoto in Angewandte Chemie International Edition in 2013, and a carbon-carbon bond is constructed through one-step intramolecular dearomatization cyclization reaction to obtain the hydrogenated pyridine spiro indoline ring. However, this method is relatively severe in conditions, and requires an extremely low temperature of-78 ℃ because an organic super base such as n-butyllithium is used.
2. Hydrogenated pyridine spiro indoline rings are obtained by fischer indole synthesis. (J.Med.chem.,2013,56,9275.)
In 2013, Jennifer X.Qiao reports on Journal of Medicinal Chemistry, a Fisher indole synthesis method is applied, aldehyde and phenylhydrazine are used for generating hydrazone, and a hydrogenated pyridine spiro indoline ring is obtained through triple rearrangement. However, this method uses an irritant and toxic reagent such as acid or methanol, and has a high reaction temperature, complicated steps and poor atom economy.
3. Hydrogenated pyridine spiro indoline rings were obtained by heck reaction. (Angew. chem. int.Ed.,2010,49,2000.)
The method was reported in 2010 by Steven m.weinreb on angeltide Chemie International Edition to undergo an intramolecular heck reaction to give a hydrogenated pyridine spiro indoline ring. However, the method has the disadvantages of complicated preparation of the substrate, severe reaction conditions, high temperature of 150 ℃, poor atom economy and more byproducts.
4. The hydrogenated pyridine spiro indoline ring is obtained through intermolecular affinity substitution and intramolecular electrophilic substitution. (Tetrahedron,2004,60,4875.)
In 2004, the method reports that Jianan-shu Xie on Tetrahedron, intermolecular affinity substitution and intramolecular electrophilic substitution reaction occur, and hydrogenated pyridine spiro indoline ring is obtained. However, the method uses strong alkali sodium hydride and strong reducing agent lithium aluminum hydride, which has certain danger and poor atom economy.
In summary, in the known synthesis method of hydrogenated pyridine spiro indoline ring, strong alkali is needed for reaction conditions, the temperature required by the reaction is high, the needed reagent is expensive, the post-treatment is troublesome and the environment is affected.
Disclosure of Invention
The technical problem solved by the invention is to provide a simple, mild and environment-friendly synthesis method of hydrogenated pyridine spiro indoline ring.
The invention develops a novel method for hydrogenating the pyridine spiro indoline ring by utilizing the characteristic that a monovalent silver catalyst can activate a triple bond, namely, the method can be directly catalyzed with various tryptamine alkynylamides substrates containing indole to generate the hydrogenated pyridine spiro indoline ring under the room temperature condition under the action of monovalent silver and a reducing agent, and has good application prospect.
The invention is realized by the following technical scheme:
the invention relates to a novel method for synthesizing a hydrogenated pyridine spiro indoline ring, which is characterized in that monovalent silver is used as a catalyst, under the room temperature condition, a tryptamine alkyne amide substrate containing indole directly generates intramolecular cyclization reaction, a reducing agent provides a hydrogen negative capture imine intermediate, and a target compound is generated, wherein the reaction general formula is as follows:
wherein the content of the first and second substances,
R1hydrogen, C1-C4 alkyl, halogen;
R2is C1-C4 alkyl, benzyl, para-substituted benzyl, the substituent isC1-C4 alkoxy;
R3C1-C4 sulfonyl and para-substituted benzenesulfonyl, wherein the substituents are C1-C4 alkyl and nitro;
R4is a substituted or unsubstituted five-membered or six-membered aromatic ring or aromatic heterocycle, wherein the aromatic heterocycle contains 1-3 heteroatoms of N, O or S, and the substituent is halogen, C1-C4 alkoxy and C1-C4 alkyl.
Preferably, the first and second electrodes are formed of a metal,
wherein R is1Is hydrogen, methyl, bromine or chlorine atom;
R2is methyl, benzyl or p-methoxybenzyl;
R3is methylsulfonyl, p-toluenesulfonyl or p-nitrobenzenesulfonyl;
R4benzene, thiophene, p-fluorine substituted benzene, p-methoxy substituted benzene, p-chlorine substituted benzene and 3-methyl substituted benzene.
The preparation process of the invention comprises the following steps:
(I) charging
Adding a tryptanthrin amide substrate containing indole and a reducing agent which is 2-3 times of the amount of the substrate substance into a solanaceous bottle together, adding a proper amount of solvent, and adding a silver catalyst which is 5% -10% of the amount of the substrate substance into the solanaceous bottle containing the substrate. The reaction solvent is toluene, the silver catalyst used in the reaction is one of silver trifluoromethanesulfonate, silver hexafluoroantimonate, silver tetrafluoroborate and silver bis (trifluoromethanesulfonyl) imide, and the reducing agent used in the reaction is hans ester.
(II) reaction
Stirring at 20-30 deg.C, preferably 25 deg.C for 1.5-9h, and detecting reaction process by thin layer chromatography. The developing agent of the thin-layer chromatography is petroleum ether, ethyl acetate and n-hexane or a mixed solution of two or three of the petroleum ether, the ethyl acetate and the n-hexane, preferably n-hexane: the ethyl acetate is 2: 1-20: 1.
(III) post-treatment of the reaction solution
Evaporating reaction medium from reaction liquid by using a rotary evaporator, and directly carrying out column chromatography separation and purification on the reaction mixture by using neutral alumina to obtain a target product, wherein the developing solvent system is as follows: petroleum ether, ethyl acetate and n-hexane or a mixture of two or three thereof, preferably n-hexane: the ethyl acetate is 2: 1-20: 1.
The method has the advantages that from the chemical perspective, the method has good atom economy, mild reaction conditions, short reaction time and simple operation; from the industrial and environmental aspects, the catalyst has low price, simple post-treatment, environmental protection, high product purity and better yield.
Detailed Description
The advantages and the preparation of the present invention will be better understood in connection with the following examples, which are intended to illustrate, but not to limit the scope of the invention.
Example 1:
adding a substrate a1(0.1mmol, 43mg) and hanster (0.2mmol,51mg) into a 25mL eggplant-shaped bottle, adding 5mL of toluene solution, then adding 1mL of toluene solution of silver trifluoromethanesulfonate (0.01mmol,2.6mg), stirring at room temperature, reacting for 2.5h, and after the reaction is finished, separating by a fast column chromatography method (n-hexane: ethyl acetate is 10:1) to obtain a target product b1 with the yield of 99%.
The reaction formula for example 1 is:
the spectral data of the product b1 were: ESI-MS (M/z):431[ M + H]+；1H-NMR(600MHz,DMSO)δ7.75(d,J＝8.1Hz,2H),7.54(d,J＝8.1Hz,2H),7.14–7.21(m,3H),7.01(td,J＝7.8,1.3Hz,1H),6.88(dd,J＝7.8,1.3Hz,2H),6.86(s,1H),6.51(d,J＝7.8Hz,1H),6.34(t,J＝7.0Hz,1H),5.86(d,J＝7.0Hz,1H),3.62(dt,J＝12.0,4.1Hz,1H),3.13(d,J＝9.2Hz,1H),3.03–3.08(m,2H),2.61(s,3H),2.48(s,3H),1.81–1.92(m,2H)。
Example 2:
adding a substrate a2(0.1mmol, 45mg) and hanster (0.2mmol,51mg) into a 25mL eggplant-shaped bottle, adding 5mL of toluene solution, then adding 1mL of toluene solution of silver trifluoromethanesulfonate (0.01mmol,2.6mg), stirring at room temperature, reacting for 2h, and after the reaction is finished, separating by using a fast column chromatography method (n-hexane: ethyl acetate is 15:1) to obtain a target product b2 with the yield of 99%.
The reaction formula of example 2 is:
the spectral data of the product b2 were: ESI-MS (M/z):449[ M + H ]]+；1H-NMR(600MHz,DMSO)δ7.74(d,J＝8.2Hz,2H),7.51(d,J＝8.2Hz,2H),6.97–7.02(m,3H),6.87–6.90(m,2H),6.82(s,1H),6.48(d,J＝7.8Hz,1H),6.33(t,J＝7.2Hz,1H),5.87(d,J＝7.2Hz,1H),3.58(dt,J＝12.1,4.2Hz,1H),3.01–3.08(m,3H),2.59(s,3H),2.46(s,3H),1.77–1.89(m,2H)。
Example 3:
adding a substrate a3(0.1mmol, 44mg) and hanster (0.2mmol,51mg) into a 25mL eggplant-shaped bottle, adding 5mL of toluene solution, then adding 1mL of toluene solution of silver trifluoromethanesulfonate (0.01mmol,2.6mg), stirring at room temperature, reacting for 2h, and after the reaction is finished, separating by using a fast column chromatography method (n-hexane: ethyl acetate is 10:1) to obtain a target product b3 with the yield of 99%.
The reaction formula of example 3 is:
the spectral data of the product b3 were: ESI-MS (M/z) 437[ M + H]+；1H-NMR(600MHz,DMSO)δ7.75(d,J＝8.1Hz,2H),7.50(d,J＝8.1,2H),7.23(dd,J＝5.1,1.0Hz,1H),7.12(s,1H),7.00–7.03(m,1H),6.82(dd,J＝5.1,3.6Hz,1H),6.55(dd,J＝3.6,1.0Hz,1H),6.49(d,J＝7.8Hz,1H),6.44(t,J＝7.2Hz,1H),6.26(d,J＝7.2Hz,1H),3.43–3.49(m,1H),3.32–3.37(m,1H),3.15(q,J＝9.4Hz,2H),2.62(s,3H),2.43(s,3H),1.94(ddd,J＝13.6,6.8,2.8Hz,1H),1.51–1.57(m,1H)。
Example 4:
adding a substrate a4(0.1mmol, 46mg) and hanster (0.2mmol,51mg) into a 25mL eggplant-shaped bottle, adding 5mL of toluene solution, then adding 1mL of toluene solution of silver trifluoromethanesulfonate (0.01mmol,2.6mg), stirring at room temperature, reacting for 1.5h, and after the reaction is finished, separating by a fast column chromatography method (n-hexane: ethyl acetate is 5:1) to obtain a target product b4 with the yield of 99%.
The reaction formula of example 4 is:
the spectral data of the product b4 were: ESI-MS (M/z):462[ M + H]+；1H-NMR(600MHz,DMSO)δ8.49–8.52(m,2H),8.15–8.18(m,2H),7.14–7.20(m,3H),7.00(td,J＝7.7,1.2Hz,1H),6.90–6.93(m,2H),6.89(s,1H),6.50(d,J＝7.8Hz,1H),6.36(td,J＝7.3,0.7Hz,1H),6.09(d,J＝7.3Hz,1H),3.69(dt,J＝12.4,4.3Hz,1H),3.20(ddd,J＝12.4,10.3,3.8Hz,1H),3.12(d,J＝9.3Hz,1H),3.05(d,J＝9.3Hz,1H),2.59(s,3H),1.80–1.89(m,2H)。
Example 5:
adding a substrate a5(0.1mmol, 36mg) and hanster (0.2mmol,51mg) into a 25mL eggplant-shaped bottle, adding 5mL of toluene solution, then adding 1mL of toluene solution of silver trifluoromethanesulfonate (0.01mmol,2.6mg), stirring at room temperature, reacting for 1.5h, and after the reaction is finished, separating by a fast column chromatography method (n-hexane: ethyl acetate is 10:1) to obtain a target product b5 with the yield of 99%.
The reaction formula of example 5 is:
the spectral data of the product b5 were: ESI-MS (M/z):355[ M + H]+；1H-NMR(600MHz,DMSO)δ7.10–7.18(m,3H),7.05–7.09(m,1H),6.97–6.99(m,2H),6.94(d,J＝7.1Hz,1H),6.78(s,1H),6.64(t,J＝7.5Hz,1H),6.56(d,J＝7.5Hz,1H),3.69(ddd,J＝12.1,5.5,3.9Hz,1H),3.46–3.51(m,1H),3.28(d,J＝9.2Hz,1H),3.17–3.20(m,4H),2.67(s,3H),1.95–2.05(m,2H)。
Example 6:
adding a substrate a6(0.1mmol, 51mg) and hanster (0.2mmol,51mg) into a 25mL eggplant-shaped bottle, adding 5mL of toluene solution, then adding 1mL of toluene solution of silver trifluoromethanesulfonate (0.01mmol,2.6mg), stirring at room temperature, reacting for 3.5h, and after the reaction is finished, separating by a fast column chromatography method (n-hexane: ethyl acetate is 15:1) to obtain a target product b6 with the yield of 90%.
The reaction formula of example 6 is:
the spectral data of the product b6 were: ESI-MS (M/z):507[ M + H]+；1H-NMR(600MHz,DMSO)δ7.75(d,J＝8.2Hz,2H),7.52(d,J＝8.2Hz,2H),7.26(t,J＝7.2Hz,2H),7.21(t,J＝7.2Hz,1H),7.17(d,J＝7.2Hz,2H),7.11–7.15(m,3H),6.98(t,J＝7.7Hz,1H),6.84–6.87(m,3H),6.55(d,J＝7.9Hz,1H),6.32(t,J＝7.3Hz,1H),5.90(d,J＝7.3Hz,1H),4.30(d,J＝15.5Hz,1H),4.18(d,J＝15.5Hz,1H),3.59(dt,J＝12.2,4.3Hz,1H),3.32(d,J＝9.4Hz,1H),3.13(ddd,J＝12.2,9.5,4.8Hz,1H),2.99(d,J＝9.4Hz,1H),2.47(s,3H),1.84–1.91(m,2H)。
Example 7:
adding a substrate a7(0.1mmol, 54mg) and hanster (0.2mmol,51mg) into a 25mL eggplant-shaped bottle, adding 5mL of toluene solution, then adding 1mL of toluene solution of silver trifluoromethanesulfonate (0.01mmol,2.6mg), stirring at room temperature, reacting for 9h, and after the reaction is finished, separating by a fast column chromatography method (n-hexane: ethyl acetate is 5:1) to obtain a target product b7 with the yield of 90%.
The reaction formula for example 7 is:
the spectral data of the product b7 were: ESI-MS (M/z):537[ M + H]+；1H-NMR(600MHz,DMSO)δ7.74(d,J＝8.2Hz,2H),7.52(d,J＝8.2Hz,2H),7.10–7.15(m,3H),7.08(d,J＝8.5Hz,2H),6.98(t,J＝7.8Hz,1H),6.80–6.85(m,5H),6.59(d,J＝7.8Hz,1H),6.30(t,J＝7.2Hz,1H),5.87(d,J＝7.2Hz,1H),4.22(d,J＝15.1Hz,1H),4.11(d,J＝15.1Hz,1H),3.71(s,3H),3.58(dt,J＝12.1,4.4Hz,1H),3.28(d,J＝9.4Hz,1H),3.12(ddd,J＝12.1,8.3,6.0Hz,1H),2.94(d,J＝9.4Hz,1H),2.47(s,3H),1.84–1.87(m,2H)。
Example 8:
adding a substrate a8(0.1mmol, 45mg) and hanster (0.2mmol,51mg) into a 25mL eggplant-shaped bottle, adding 5mL of toluene solution, then adding 1mL of toluene solution of silver trifluoromethanesulfonate (0.01mmol,2.6mg), stirring at room temperature, reacting for 2h, and after the reaction is finished, separating by a fast column chromatography method (n-hexane: ethyl acetate is 10:1) to obtain a target product b8 with the yield of 99%.
The reaction formula for example 8 is:
the spectral data of the product b8 were: ESI-MS (M/z):445[ M + H]+；1H-NMR(600MHz,DMSO)δ7.73(d,J＝8.2Hz,2H),7.52(d,J＝8.2Hz,2H),7.12–7.21(m,3H),6.86–6.89(m,2H),6.82(s,1H),6.32(s,1H),6.14(d,J＝7.4Hz,1H),5.72(d,J＝7.4Hz,1H),3.61(dt,J＝12.0,4.0Hz,1H),3.09(d,J＝9.1Hz,1H),2.98–3.04(m,2H),2.57(s,3H),2.47(s,3H),2.17(s,3H),1.76–1.88(m,2H)。
Example 9:
adding a substrate a9(0.1mmol, 51mg) and hanster (0.2mmol,51mg) into a 25mL eggplant-shaped bottle, adding 5mL of toluene solution, then adding 1mL of toluene solution of silver trifluoromethanesulfonate (0.01mmol,2.6mg), stirring at room temperature, reacting for 5h, and after the reaction is finished, separating by a fast column chromatography method (n-hexane: ethyl acetate is 10:1) to obtain a target product b9 with the yield of 96%.
The reaction formula for example 9 is:
the spectral data of the product b9 were: ESI-MS (M/z) 511[ M + H]+；1H-NMR(600MHz,DMSO)δ7.72(d,J＝8.2Hz,2H),7.41(d,J＝8.2Hz,2H),7.18–7.20(m,2H),7.16(dd,J＝8.3,1.8Hz,1H),7.08(s,1H),6.89–6.93(m,2H),6.34(d,J＝8.3Hz,1H),6.14(d,J＝1.8Hz,1H),3.77(dt,J＝12.0,3.8Hz,1H),3.33(d,J＝9.2Hz,1H),2.97–3.04(m,2H),2.65(s,3H),2.48(s,3H),1.94–2.06(m,2H)。
Example 10:
adding a substrate a10(0.1mmol, 47mg) and hanster (0.2mmol,51mg) into a 25mL eggplant-shaped bottle, adding 5mL of toluene solution, then adding 1mL of toluene solution of silver trifluoromethanesulfonate (0.01mmol,2.6mg), stirring at room temperature, stirring for reaction for 4h, and after the reaction is finished, separating by a fast column chromatography method (n-hexane: ethyl acetate is 15:1) to obtain a target product b10 with the yield of 99%.
The reaction formula for example 10 is:
the spectral data of the product b10 were: ESI-MS (M/z):465[ M + H]+；1H-NMR(600MHz,DMSO)δ7.74(d,J＝8.1Hz,2H),7.52(d,J＝8.1Hz,2H),7.15–7.23(m,3H),7.01(dd,J＝8.4,2.0Hz,1H),6.85–6.90(m,3H),6.50(d,J＝8.4Hz,1H),5.78(d,J＝2.0Hz,1H),3.64(dt,J＝11.7,3.8Hz,1H),3.18(d,J＝9.4Hz,1H),3.09(d,J＝9.4Hz,1H),2.95(td,J＝11.7,2.8Hz,1H),2.60(s,3H),2.43(s,3H),1.83–1.98(m,2H)。
Claims (7)
1. A method for synthesizing a hydrogenated pyridine spiro indoline ring under catalysis of monovalent silver is characterized by comprising the following steps: under the catalysis of monovalent silver, an indole-containing tryptamine alkynylamide substrate undergoes an intramolecular cyclization reaction at room temperature, and then a reducing agent provides a hydrogen negative capture imine intermediate to generate a hydrogenated pyridine spiro indoline ring, wherein the reaction formula is as follows:
wherein the content of the first and second substances,
R1hydrogen, C1-C4 alkyl, halogen;
R2is C1-C4 alkyl, benzyl, para-substituted benzyl, and the substituent is C1-C4 alkoxy;
R3C1-C4 sulfonyl and para-substituted benzenesulfonyl, wherein the substituents are C1-C4 alkyl and nitro;
R4is a substituted or unsubstituted five-membered or six-membered aromatic ring or aromatic heterocycle, the aromatic heterocycle contains 1-3 heteroatoms of N, O or S, and the substituent is halogen, C1-C4 alkoxy, C1-C4 alkyl;
the silver catalyst used in the reaction is one of silver trifluoromethanesulfonate, silver hexafluoroantimonate, silver tetrafluoroborate and silver bis (trifluoromethanesulfonyl) imide, and the reducing agent used in the reaction is hans ester.
2. The method of synthesis according to claim 1,
R1is hydrogen, methyl, bromine or chlorine atom;
R2is methyl, benzyl or p-methoxybenzyl;
R3is methylsulfonyl, p-toluenesulfonyl or p-nitrobenzenesulfonyl;
R4is benzene, substituted benzene or thiophene, and the substituent is halogen, C1-C4 alkoxy and C1-C4 alkyl.
3. The method of synthesis of claim 1, wherein:
R1is a bromine atom, a chlorine atom or a methyl group substituted at the 5-position;
R2is methyl, benzyl, p-methoxybenzyl;
R3p-toluenesulfonyl, p-nitrobenzenesulfonyl, methanesulfonyl;
R4is thiophene ring, benzene ring, p-fluorine substituted benzene, p-methoxy substituted benzene, p-chlorine substituted benzene, and 3-methyl substituted benzene.
4. The method of synthesis according to claim 1, comprising the steps of:
(1) charging of
Adding a tryptanthrin amide substrate containing indole and a reducing agent which is 2-3 times of the amount of the substrate substance into a solanaceous bottle together, adding a proper amount of solvent, adding a silver catalyst which is 5% -10% of the amount of the substrate substance into the solanaceous bottle containing the substrate, wherein the reaction solvent is toluene, the silver catalyst used in the reaction is one of silver trifluoromethanesulfonate, silver hexafluoroantimonate, silver tetrafluoroborate and silver bistrifluoromethanesulfonimide, and the reducing agent used in the reaction is hans ester;
(2) reaction of
Stirring and reacting for 1.5-9h at 25 ℃, and monitoring the reaction process by thin layer chromatography;
(3) post-treatment of the reaction solution
And (3) evaporating the reaction liquid out of the reaction medium by using a rotary evaporator, and directly performing column chromatography separation and purification on the reaction mixture by using neutral alumina to obtain the target product.
5. The method of synthesis of claim 4, wherein: and (3) developing agent of the thin-layer chromatography in the step (2) is petroleum ether, ethyl acetate, n-hexane or mixture of two or three of the petroleum ether, the ethyl acetate and the n-hexane.
6. The method of synthesis of claim 4, wherein: the system of the column chromatography separation and purification developing solvent in the step (3) is as follows: petroleum ether, ethyl acetate, n-hexane or a mixture of two or three of them.
7. The synthesis process according to claim 5 or 6, characterized in that the ratio of the developing solvent is n-hexane: ethyl acetate was 2: 1-20:1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710670364.4A CN109384787B (en) | 2017-08-08 | 2017-08-08 | Method for synthesizing hydrogenated pyridine spiro indoline ring under catalysis of monovalent silver |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710670364.4A CN109384787B (en) | 2017-08-08 | 2017-08-08 | Method for synthesizing hydrogenated pyridine spiro indoline ring under catalysis of monovalent silver |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109384787A CN109384787A (en) | 2019-02-26 |
| CN109384787B true CN109384787B (en) | 2021-04-16 |
Family
ID=65413368
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710670364.4A Active CN109384787B (en) | 2017-08-08 | 2017-08-08 | Method for synthesizing hydrogenated pyridine spiro indoline ring under catalysis of monovalent silver |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109384787B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111018864A (en) * | 2019-12-24 | 2020-04-17 | 温州大学新材料与产业技术研究院 | Preparation method of indole-fused octamer lactam compound |
| CN115785087B (en) * | 2021-09-09 | 2024-02-27 | 沈阳药科大学 | Synthesis method of monovalent gold catalyzed 1H-pyrido [4,3-b ] indole skeleton compound |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8236963B2 (en) * | 2005-05-24 | 2012-08-07 | Merck Serono Sa | Tricyclic spiro derivatives as CRTH2 modulators |
-
2017
- 2017-08-08 CN CN201710670364.4A patent/CN109384787B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN109384787A (en) | 2019-02-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Bugaenko et al. | Synthesis of indoles: recent advances | |
| Ryzhakov et al. | Radical-mediated dearomatization of indoles with sulfinate reagents for the synthesis of fluorinated spirocyclic indolines | |
| Peat et al. | Novel syntheses of tetrahydropyrroloquinolines: Applications to alkaloid synthesis | |
| Sridharan et al. | Advances in the chemistry of tetrahydroquinolines | |
| Ganesh et al. | Catalytic enantioselective additions of indoles to nitroalkenes | |
| Cai et al. | Substrate-controlled transformation of azobenzenes to indazoles and indoles via rh (III)-catalysis | |
| Liu et al. | Asymmetric organocatalytic conjugate addition of dialkyl phosphites to N-unprotected isatylidene malononitriles: access to 3-phospho-2-oxindoles with chiral quaternary stereocenters | |
| Yin et al. | Asymmetric synthesis of tetrahydro-β-carbolines via chiral phosphoric acid catalyzed transfer hydrogenation reaction | |
| Lin et al. | Microwave-assisted regioselective synthesis of 3-functionalized indole derivatives via three-component domino reaction | |
| Miao et al. | 2-Oxindole acts as a synthon of 2-aminobenzoyl anion in the K2CO3-catalyzed reaction with enones: preparation of 1, 4-diketones bearing an amino group and their further transformations | |
| Moskowitz et al. | Catalytic enantioselective ynamide additions to isatins: Concise access to oxindole alkaloids | |
| Amat et al. | Conjugate additions to phenylglycinol-derived unsaturated δ-lactams. Enantioselective synthesis of uleine alkaloids | |
| Simlandy et al. | Catalytic Enantioselective Synthesis of 3, 4-Unsubstituted Thiochromenes through Sulfa-Michael/Julia–Kocienski Olefination Cascade Reaction | |
| Wan et al. | Ag (i)-Catalyzed oxidative decarboxylation of difluoroacetates with activated alkenes to form difluorooxindoles | |
| Thakur et al. | “On water” catalyst-free, column chromatography-free and atom economical protocol for highly diastereoselective synthesis of novel class of 3-substituted, 3-hydroxy-2-oxindole scaffolds at room temperature | |
| CN109384787B (en) | Method for synthesizing hydrogenated pyridine spiro indoline ring under catalysis of monovalent silver | |
| Zheng et al. | Pd-catalyzed arylperfluoroalkylation of unactivated olefins for the synthesis of heterocycles | |
| Ying et al. | Site-selective carbonylative synthesis of structurally diverse lactams from heterocyclic amines with TFBen as the CO source | |
| CN109384789B (en) | Synthesis method of indolocazaheptatomic ring catalyzed by monovalent silver | |
| Feng et al. | Tunable Synthesis of Functionalized Cyclohexa-1, 3-dienes and 2-Aminobenzophenones/Benzoate from the Cascade Reactions of Allenic Ketones/Allenoate with Amines and Enones | |
| CN110526795A (en) | The butylene lactone or butylene lactam compound and its method of asymmetric synthesis and ligand that γ-alkenyl replaces | |
| Xu et al. | Pd‐Catalyzed Asymmetric Allylic Substitution Annulation Using Enolizable Ketimines as Nucleophiles: An Alternative Approach to Chiral Tetrahydroindoles | |
| Samanta et al. | Transition metal-free advanced synthetic approaches for isoindolinones and their fused analogues | |
| CN107235992B (en) | Indolone spiral shell thiophane class compound and its salt, preparation method and application | |
| Chen et al. | Synthesis of Tetrahydro-2 H-thiopyran 1, 1-Dioxides via [1+ 1+ 1+ 1+ 1+ 1] Annulation: An Unconventional Usage of a Tethered C–S Synthon |
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 |