CN113480544A - Alkynyl imidazo [1,5-a ] indole compound and preparation method thereof - Google Patents
Alkynyl imidazo [1,5-a ] indole compound and preparation method thereof Download PDFInfo
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Abstract
The invention provides alkynyl imidazo [1,5-a ]]An indole compound and a preparation method thereof, belonging to the technical field of organic synthesis. The invention adopts rhodium to catalyze the generation of [4+1] between indole and alpha, alpha-difluoromethylene alkyne]Cyclization/alkynyl migration tandem reaction to synthesize a series of alkynylated imidazo [1,5-a]Indole compound, wherein the catalyst is [ Cp + RhCl2]2The additive is potassium fluoride, and the solvent is methanol; the mol ratio of the indole to the alpha, alpha-difluoromethylene alkyne is 1:1.3, the addition amount of the catalyst is 5% of the mol amount of the indole, and the mol ratio of the additive to the indole is 1:1. The synthesis method provided by the invention has the advantages of wide substrate application range, high chemoselectivity and regioselectivity, good yield, good functional group tolerance, economic reaction steps, mild neutral reaction conditions and the like. The alkynylated imidazo [1,5-a]The structural formula of the indole compound is:
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to an alkynylated imidazo [1,5-a ] indole compound and a preparation method thereof.
Background
Indole fused ring compounds widely exist in active natural products and drug molecules and show important application value, so that methods for constructing compounds with the structures attract extensive attention of chemists. Most of the traditional methods for constructing the structure involve multi-step functional group conversion reaction, and need to separate and purify for many times, and have the defects of complicated steps, low total yield and the like. In recent years, the C-H activation reaction assisted by a guide group and catalyzed by a transition metal is rapidly developed, compared with the traditional synthesis method, the C-H activation reaction catalyzed by the transition metal does not need to pre-functionalize a substrate, and can rapidly realize direct functionalization of an inert C-H bond in one step, so that the method has the advantages of simple and easily obtained starting materials, few synthesis steps, high synthesis efficiency and the like. Under the background, C-H cyclization reaction between indole substrates and various reagents becomes a powerful tool for quickly and efficiently constructing indole fused ring compounds.
It is worth noting that among a plurality of indole fused ring compounds, the compounds with imidazo [1,5-a ] indole parent nucleus are widely embodied in pharmacologically active molecules, so that the compounds with the parent nucleus structures have important potential application values. Representative active compounds having an imidazo [1,5-a ] indole nucleus have the following structural formula:
however, the methods for constructing imidazo [1,5-a ] indole by C-H cyclization reaction between indole substrates and various reagents reported at present have some obvious disadvantages, such as the need of using dangerous diazo compounds or malodorous isonitrile as a reaction reagent, the need of using exogenous metallic or non-metallic oxidant, narrow substrate application range, low yield, harsh reaction conditions and the like. In addition, a search of the prior art documents revealed no method for producing alkynylated imidazo [1,5-a ] indoles. Therefore, it is an urgent technical problem to be solved by the present invention to develop a method for preparing alkynylated imidazo [1,5-a ] indoles, and to provide a synthetic method which has the advantages of friendly and easily available reaction reagents, no need of exogenous oxidants, wide substrate application range, excellent yield, and mild reaction conditions.
Disclosure of Invention
The purpose of the invention is to solve the technical problems, and thus to provide an alkynylated imidazo [1,5-a ] indole compound and a preparation method thereof.
It is an object of the present invention to provide a process for the preparation of an alkynylated imidazo [1,5-a ] indole compound of formula (III), which comprises the steps of:
in the formula<Ⅰ>Indole compounds and compounds of formula<Ⅱ>The alpha, alpha-difluoromethylene alkyne compound is used as a substrate and takes [ Cp RhCl2]2Is taken as a catalyst, potassium fluoride is taken as an additive, methanol is taken as a solvent, and the reaction is carried out for 9 to 30 hours at the temperature of 60 ℃ to obtain the formula<Ⅲ>A compound shown as the formula (I);
the equation for the above synthesis reaction is as follows:
wherein R is1Represents a substituent at any position on the phenyl ring selected from the group consisting of: hydrogen, halogen, alkyl, alkoxy, ester groups;
R2selected from the following groups: hydrogen, substitutionOr unsubstituted alkyl;
R3selected from the following groups: substituted or unsubstituted alkyl;
R4selected from the following groups: substituted or unsubstituted alkyl;
R5selected from the following groups: substituted or unsubstituted alkyl, aryl;
the substitution means that one or more hydrogen atoms on the group are substituted with a substituent selected from the group consisting of: phenyl, ester, acetamido, benzyloxy, hydroxy, p-methoxybenzyloxy, tetrahydro-2H-pyran-2-yl) oxy, halogen, acetoxy, 1, 3-dicarbonylisoindolin-2-yl.
The invention develops a rhodium-catalyzed [4+1] cyclization/alkynyl migration tandem reaction between indole and alpha, alpha-difluoromethylene alkyne, and successfully prepares a series of compounds with alkynyl imidazo [1,5-a ] indole parent nucleus. The reaction has the advantages of wide substrate application range, high chemical selectivity and regioselectivity, good yield, good functional group tolerance, economic reaction steps, mild neutral reaction conditions and the like, and has wide application prospect.
Further, the halogen includes F, Cl, Br or I.
Further, the alkyl group includes methyl, ethyl, isopropyl, n-butyl or cyclohexyl, and the alkoxy group includes methoxy or ethoxy; the aryl group includes phenyl. The substituted alkyl group includes the specific description of the alkyl substituent groups in the examples, but is not limited to these substituted alkyl groups.
Further, the molar ratio of the compound I to the compound II is 1: 1.3.
Furthermore, the amount of the catalyst is 1 to 10 percent, preferably 5 percent (in the embodiment, the amount is 5 percent for example) of the molar amount of the compound I.
Further, the molar ratio of the additive to the compound I is 1:1.
The invention also aims to provide the alkynylated imidazo [1,5-a ] indole compound shown in the formula (III) prepared by the method. And a series of compounds III that have been successfully synthesized are provided in the examples of the present invention and characterized.
The invention has the following beneficial effects:
the invention develops a rhodium-catalyzed [4+1] cyclization/alkynyl migration tandem reaction between indole and alpha, alpha-difluoromethylene alkyne, and successfully prepares a series of compounds with alkynyl imidazo [1,5-a ] indole parent nucleus. The method has the advantages of wide substrate application range, high chemical selectivity and regioselectivity, good yield, good functional group tolerance, economic reaction steps, mild neutral reaction conditions and the like, can be amplified to gram-scale, and has better practicability. In addition, the synthesis method provided by the invention can also be applied to structure modification of natural products such as Melatonin (Melatonin), and has wide application prospect.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more clearly understood, the present invention is described in detail below with reference to the following embodiments, and it should be noted that the following embodiments are only for explaining and illustrating the present invention and are not intended to limit the present invention. The invention is not limited to the embodiments described above, but rather, may be modified within the scope of the invention.
Example 1
Optimization of reaction conditions: according to the following reaction formula, the reaction conditions are optimized according to the steps shown in table 1 by using the compounds 1aa and 2aa as template substrates, and the steps comprise sequentially optimizing a catalyst, a solvent and an additive.
Firstly, NaOAc is used as an additive, and 1aa and 2aa react for 9 hours (serial numbers 1-5) in methanol at 60 ℃ under the catalysis of a series of metal catalysts. The results show that [ Cp RhCl ] is used2]2When used as a catalyst, the target [4+1] is obtained]Cyclization/alkynyl migration tandem reaction product 3aa, 69% yield, good chemo-and regio-selectivity (No. 5).
Then, the reaction solution is respectively added with [ Cp + RhCl2]2And NaOAc as a catalyst and additive, the effect of different solvents on the yield of the desired product was examined (serial numbers 6-13). The results show that in addition to EtOH, 4aa is more favored over 3aa for C-H olefination/directing group migration by-product in aprotic solvents. It is noted that the yield of the by-product 4aa in 1, 4-dioxane reached 79% (No. 11).
Subsequently, a series of additives were screened in MeOH as solvent in order to further increase the yield of the target product 3aa (nos. 14-22), and the results showed that: when KF was used as the additive, the yield of the product 3aa was the best and reached 78% (No. 22). Finally, the blank experiments showed that both the catalyst and the additive are critical to the above reaction (numbers 23 and 24). Thus, [ Cp + RhCl ] was determined2]2A catalyst system consisting of KF/MeOH, wherein the catalyst system realizes the target of [4+1]]Key to the cyclization/alkyne mobilization cascade.
TABLE 1 reaction condition optimizationa
aReaction conditions are as follows: 1aa (0.25mmol), 2aa (0.325mmol), catalyst (5 mol%), additive (0.25mmol), solvent (4.0mL), reaction temperature 60 ℃, reaction time 9 h;bmeans the isolated yield;crefer to the data after 1 h.
Example 2
Under the above-mentioned optimum reaction conditions (No. 22), the substrate application range of Rh (III) -catalyzed [4+1] cyclization/alkynyl migration tandem reaction was investigated, and the results are shown in Table 2.
TABLE 2 Rh (III) catalyzed [4+1]]Substrate range applicable to cyclization/alkynyl migration tandem reactiona,b
aReaction conditions are as follows: unless otherwise stated, 1(0.25mmol),2(0.325mmol), [ Cp + RhCl2]2(5 mol%) and KF (0.25mmol) in MeOH (4.0mL) at 60 ℃ for 9 h;brefers to the isolated yield.
Firstly, 2aa is used as a template alkyne substrate, and the application range of the indole substrate is examined. For example, halogen (F, Cl, Br, I) substituted indoles can be reacted smoothly and yield the product 3ab-3ah in 53-71% yield; similarly, the indole substituted with an electron donating group such as Me, MeO, EtO, etc. was successfully reacted to give the product 3ai-3ao in 68-76% yield. Electron withdrawing group CO2The Me substituted indole also allowed the reaction to proceed and gave the product 3ap in 36% yield. It is noteworthy that, despite the steric hindrance caused by the substituent at position C3, the C3 substituted indole was able to participate in this reaction and gave the corresponding product 3aq-3as in 55-72% yield. In addition, except for being bulkytOutside the Bu group, in R3In position with an alkyl group such as Et,iPr and Bn substituted indoles can be successfully converted into corresponding products of 3at, 3au and 3aw, and the yield is 37-86%.
Next, the substrate range of α, α -difluoromethylenealkyne was examined using indole 1aa as a template indole substrate. R4Hydroxy or chloro substituted alkyl substituted alpha, alpha-difluoromethylene alkyne with phenyl (Ph), free or p-methoxybenzyl (PMB)/tetrahydro-2H-pyran-2-yl (THP)/benzyl (Bn) protection in position can be reacted smoothly to obtain the product 3ax-3bc with a yield of 38-76%. Also at R5The reaction of alpha, alpha-difluoromethylene alkyne carrying alkyl or aryl at the position is also active, and the target product 3bd-3bf can be obtained with the yield of 70-85%. The reaction pair is in R5In position by introduction of free or acetyl groupsAlkyne substrates of hydroxy group protected with group (Ac), amino group substituted with phthalyl protected (NPhth) alkyl chain are equally suitable, giving the product 3bg-3bi in 65-80% yield. Interestingly, R in alkyne 2aa4And R5When the positions of the groups are interchanged, the reaction can still obtain the target product 3bj with 65% yield.
Notably, this reaction can be applied to structural modification of natural products. For example, melatonin, an animal hormone, was successfully obtained in 71% yield from the melatonin derivative 3bk by carbamylation followed by rh (iii) -catalyzed [4+1] cyclization/alkyne migration cascade with alkyne 2 aa. In addition, pyrrole substrate can also participate in this conversion, and successfully get the product 3bl and 3bm, yield 65% and 66% respectively.
In summary, in R1-R3Indole 1 carrying different substituents at the positions with R4-R5Alpha, alpha-difluoromethylene alkyne 2 with different substituents at the positions can smoothly react to obtain a series of alkynyl imidazo [1,5-a ]]Indole compound 3, the yield is good, and excellent chemo-and regioselectivity is shown.
The results show that the rhodium-catalyzed cyclization/alkynyl migration tandem reaction between indole and alpha, alpha-difluoromethylene alkyne [4+1] has the advantages of wide substrate application range, high chemoselectivity and regioselectivity, good yield, good functional group tolerance, economic reaction steps, mild neutral reaction conditions and the like, and can efficiently synthesize a series of compounds 3 with alkynyl imidazo [1,5-a ] indole parent nucleus.
Example 3
Gram-scale amplification reaction experiment: a gram-scale amplification reaction carried out under the following reaction conditions, using 1aa (6mmol) and 2aa (7.8mmol), gave the desired product 3aa in 73% yield. This demonstrates that the reaction between 1aa and 2aa can be scaled up to gram scale without loss of efficiency, indicating the utility and industrial application prospects of the reaction.
Example 4
Specific characterization of the series of compounds 3 prepared in example 2:
indole 1(0.25mmol) and [ Cp × RhCl ] were added to a 25mL Schlenk tube in this order according to the following procedure2]2(5 mol%) and KF (0.25mmol), and a solution of α, α -difluoromethylenealkyne 2(0.325mmol) in methanol (4.0mL) was added thereto, and then the tube was sealed with a lid, and the resulting reaction mixture was stirred in an oil bath at 60 ℃ for the reaction time shown in Table 2. After the reaction is finished, the reaction solvent is removed by decompression and concentration, and the obtained residue is purified by flash chromatography on silica gel to obtain the target product 3. Successfully prepares a series of alkynylated imidazo [1,5-a ] according to the method]The indole parent nucleus compound 3 (compound one to thirty eight) is characterized by adopting a hydrogen spectrum, a carbon spectrum and a high-resolution mass spectrum, and the obtained compound has the following characterization results:
compound one (3 aa):
1-butyl-2-methoxy-1- (4-phenylbut-1-yn-1-yl) -1,2-dihydro-3H-imidazo [1,5-a ] indol-3-one 1-butyl-2-methoxy-1- (4-phenylbut-1-yn-1-yl) -1, 2-dihydro-3H-imidozo [1,5-a ] indol-3-one
The reaction mixture was directly subjected to flash chromatography on silica gel (petroleum/ethyl acetate: 40/1) to give a yellow colorless viscous oil (75.7mg, yield 78%).
1H NMR(600MHz,CDCl3)δ7.98(d,J＝8.1Hz,1H),7.60(d,J＝7.9Hz,1H),7.35-7.31(m,1H),7.31-7.26(m,3H),7.24-7.18(m,3H),6.39(s,1H),4.00(s,3H),2.84(t,J＝7.3Hz,2H),2.57(t,J＝7.3Hz,2H),2.20-2.12(m,1H),2.05-1.97(m,1H),1.36-1.27(m,3H),1.22-1.11(m,1H),0.86(t,J＝7.1Hz,3H)；13C NMR(150MHz,CDCl3)δ151.17,140.29,137.63,132.58,130.88,128.63,128.49,126.52,124.01,123.31,121.41,113.14,99.01,85.28,78.18,65.88,61.13,38.64,34.67,25.82,22.45,20.87,13.96；HRMS(ESI)m/z:[M+H]+Calculated for C25H27N2O2 +387.2067；Found 387.2064.
Compound two (3 ab):
1-butyl-7-fluoro-2-methoxy-1- (4-phenylbut-1-yn-1-yl) -1,2-dihydro-3H-imidazo [1,5-a ] indol-3-one
1-butyl-7-fluoro-2-methoxy-1-(4-phenylbut-1-yn-1-yl)-1,2-dihydro-3H-imidazo[1,5-a]indol-3-one
The reaction mixture was directly subjected to flash chromatography on silica gel (petroleum/ethyl acetate: 40/1) to give a yellow viscous oil (64.1mg, yield 63%).
1H NMR(600MHz,CDCl3)δ7.89(dd,J＝8.9,4.5Hz,1H),7.31-7.18(m,6H),7.09-7.03(m,1H),6.34(s,1H),3.98(s,3H),2.84(t,J＝7.3Hz,2H),2.56(t,J＝7.3Hz,2H),2.19-2.10(m,1H),2.03-1.95(m,1H),1.34-1.26(m,3H),1.18-1.09(m,1H),0.86(t,J＝7.1Hz,3H)；13C NMR(150MHz,CDCl3)δ159.66(d,JC-F＝239.1Hz),150.88,140.25,139.34,133.42(d,JC-F＝10.4Hz),128.63,128.51,127.30,126.56,113.89(d,JC-F＝9.8Hz),112.13(d,JC-F＝25.9Hz),107.03(d,JC-F＝24.2Hz),98.93(d,JC-F＝4.3Hz),85.52,77.91,65.93,61.11,38.60,34.63,25.82,22.44,20.86,13.97；HRMS(ESI)m/z:[M+H]+Calculated for C25H26FN2O2 +405.1973；Found405.1971.
Compound three (3 ac):
1-butyl-7-chloro-2-methoxy-1- (4-phenylbut-1-yn-1-yl) -1,2-dihydro-3H-imidazo [1,5-a ] indol-3-one
1-butyl-7-chloro-2-methoxy-1-(4-phenylbut-1-yn-1-yl)-1,2-dihydro-3H-imidazo[1,5-a]indol-3-one
The reaction mixture was directly subjected to flash chromatography on silica gel (petroleum/ethyl acetate: 40/1) to give a yellow viscous oil (61.1mg, 58% yield).
1H NMR(600MHz,CDCl3)δ7.88(d,J＝8.6Hz,1H),7.57(d,J＝2.0Hz,1H),7.30-7.27(m,3H),7.24-7.18(m,3H),6.32(s,1H),3.98(s,3H),2.83(t,J＝7.3Hz,2H),2.56(t,J＝7.3Hz,2H),2.18-2.10(m,1H),2.04-1.95(m,1H),1.31-1.26(m,3H),1.16-1.08(m,1H),0.86(t,J＝7.1Hz,3H)；13C NMR(150MHz,CDCl3)δ150.71,140.23,138.99,133.68,129.19,128.96,128.63,128.52,126.57,124.34,121.07,113.99,98.46,85.61,77.83,65.94,61.11,38.61,34.62,25.79,22.42,20.85,13.96；HRMS(ESI)m/z:[M+H]+Calculated for C25H26ClN2O2 +421.1677；Found421.1679.
Compound four (3 ad):
7-bromo-1-butyl-2-methoxy-1- (4-phenylbut-1-yn-1-yl) -1,2-dihydro-3H-imidazo [1,5-a ] indol-3-one
7-bromo-1-butyl-2-methoxy-1-(4-phenylbut-1-yn-1-yl)-1,2-dihydro-3H-imidazo[1,5-a]indol-3-one
The reaction mixture was directly subjected to flash chromatography on silica gel (petroleum/ethyl acetate: 40/1) to give a yellow viscous oil (61.2mg, 53% yield).
1H NMR(600MHz,CDCl3)δ7.83(d,J＝8.6Hz,1H),7.73(d,J＝1.8Hz,1H),7.42(dd,J＝8.6,1.9Hz,1H),7.31-7.26(m,2H),7.24-7.17(m,3H),6.31(s,1H),3.98(s,3H),2.83(t,J＝7.3Hz,2H),2.56(t,J＝7.3Hz,2H),2.20-2.08(m,1H),2.04-1.94(m,1H),1.32-1.26(m,3H),1.15-1.06(m,1H),0.85(t,J＝7.1Hz,3H)；13C NMR(150MHz,CDCl3)δ150.68,140.23,138.84,134.20,129.52,128.63,128.52,126.97,126.58,124.13,116.58,114.40,98.32,85.64,77.83,65.95,61.09,38.63,34.62,25.79,22.42,20.85,13.96；HRMS(ESI)m/z:[M+H]+Calculated for C25H26BrN2O2 +465.1172；Found 465.1169.
Compound five (3 ae):
1-butyl-7-iodo-2-methoxy-1- (4-phenylbut-1-yn-1-yl) -1,2-dihydro-3H-imidazo [1,5-a ] indol-3-one
1-butyl-7-iodo-2-methoxy-1-(4-phenylbut-1-yn-1-yl)-1,2-dihydro-3H-imidazo[1,5-a]indol-3-one
The reaction mixture was directly subjected to flash chromatography on silica gel (petroleum/ethyl acetate: 40/1) to give a yellow viscous oil (70.5mg, 55% yield).
1H NMR(600MHz,CDCl3)δ7.94(d,J＝1.6Hz,1H),7.73(d,J＝8.5Hz,1H),7.59(dd,J＝8.5,1.6Hz,1H),7.31-7.26(m,2H),7.24-7.18(m,3H),6.29(s,1H),3.97(s,3H),2.83(t,J＝7.3Hz,2H),2.56(t,J＝7.3Hz,2H),2.20-2.07(m,1H),2.04-1.93(m,1H),1.30-1.26(m,3H),1.14-1.05(m,1H),0.85(t,J＝7.1Hz,3H)；13C NMR(150MHz,CDCl3)δ150.68,140.23,138.44,134.77,132.53,130.31,130.00,128.63,128.52,126.58,114.82,98.01,87.19,85.63,77.82,65.95,61.05,38.62,34.61,25.78,22.41,20.85,13.96；HRMS(ESI)m/z:[M+H]+Calculated for C25H26IN2O2 +513.1033；Found 513.1027.
Compound six (3 af):
1-butyl-6-fluoro-2-methoxy-1- (4-phenylbut-1-yn-1-yl) -1,2-dihydro-3H-imidazo [1,5-a ] indol-3-one
1-butyl-6-fluoro-2-methoxy-1-(4-phenylbut-1-yn-1-yl)-1,2-dihydro-3H-imidazo[1,5-a]indol-3-one
The reaction mixture was directly subjected to flash chromatography on silica gel (petroleum/ethyl acetate: 40/1) to give a pale yellow viscous oil (72.0mg, yield 71%).
1H NMR(600MHz,CDCl3)δ7.67(dd,J＝8.8,2.4Hz,1H),7.51(dd,J＝8.7,5.0Hz,1H),7.31-7.26(m,2H),7.24-7.18(m,3H),7.05-6.98(m,1H),6.35(s,1H),3.98(s,3H),2.83(t,J＝7.3Hz,2H),2.56(t,J＝7.3Hz,2H),2.18-2.10(m,1H),2.02-1.95(m,1H),1.33-1.27(m,3H),1.19-1.11(m,1H),0.86(t,J＝7.1Hz,3H)；13C NMR(150MHz,CDCl3)δ160.53(d,JC-F＝241.6Hz),150.73,140.26,137.87(d,JC-F＝3.8Hz),130.81(d,JC-F＝13.0Hz),128.79,128.63,128.51,126.55,122.13(d,JC-F＝9.9Hz),111.79(d,JC-F＝24.3Hz),100.32(d,JC-F＝27.4Hz),98.79,85.43,78.02,65.93,61.16,38.64,34.65,25.82,22.45,20.87,13.98.；HRMS(ESI)m/z:[M+H]+Calculated for C25H26FN2O2 +405.1973；Found 405.1965.
Compound seven (3 ag):
1-butyl-6-chloro-2-methoxy-1- (4-phenylbut-1-yn-1-yl) -1,2-dihydro-3H-imidazo [1,5-a ] indol-3-one
1-butyl-6-chloro-2-methoxy-1-(4-phenylbut-1-yn-1-yl)-1,2-dihydro-3H-imidazo[1,5-a]indol-3-one
The reaction mixture was directly subjected to flash chromatography on silica gel (petroleum/ethyl acetate: 40/1) to give a yellow viscous oil (58.3mg, 55% yield).
1H NMR(600MHz,CDCl3)δ7.97(d,J＝1.9Hz,1H),7.49(d,J＝8.4Hz,1H),7.29-7.26(m,2H),7.25-7.21(m,2H),7.21-7.18(m,2H),6.34(s,1H),3.98(s,3H),2.83(t,J＝7.3Hz,2H),2.56(t,J＝7.3Hz,2H),2.17-2.10(m,1H),2.03-1.95(m,1H),1.32-1.27(m,3H),1.16-1.07(m,1H),0.85(t,J＝7.1Hz,3H)；13C NMR(150MHz,CDCl3)δ150.60,140.22,138.11,131.07,130.98,129.95,128.62,128.50,126.55,123.97,122.16,113.30,98.82,85.55,77.86,65.94,61.13,38.61,34.61,25.79,22.42,20.85,13.97；HRMS(ESI)m/z:[M+H]+Calculated for C25H26ClN2O2 +421.1677；Found 421.1679.
Compound eight (3 ah):
6-bromo-1-butyl-2-methoxy-1- (4-phenylbut-1-yn-1-yl) -1,2-dihydro-3H-imidazo [1,5-a ] indol-3-one
6-bromo-1-butyl-2-methoxy-1-(4-phenylbut-1-yn-1-yl)-1,2-dihydro-3H-imidazo[1,5-a]indol-3-one
The reaction mixture was directly subjected to flash chromatography on silica gel (petroleum/ethyl acetate: 40/1) to give a yellow viscous oil (64.4mg, 55% yield).
1H NMR(600MHz,CDCl3)δ8.14(d,J＝1.7Hz,1H),7.45(d,J＝8.4Hz,1H),7.37(dd,J＝8.4,1.8Hz,1H),7.30-7.26(m,2H),7.24-7.18(m,3H),6.34(s,1H),3.98(s,3H),2.83(t,J＝7.3Hz,2H),2.56(t,J＝7.3Hz,2H),2.18-2.09(m,1H),2.04-1.94(m,1H),1.32-1.27(m,3H),1.16-1.07(m,1H),0.85(t,J＝7.1Hz,3H)；13C NMR(150MHz,CDCl3)δ150.56,140.22,138.02,131.40,131.34,128.62,128.50,126.62,126.55,122.54,117.46,116.21,98.86,85.56,77.81,65.95,61.12,38.59,34.61,25.78,22.41,20.85,13.97；HRMS(ESI)m/z:[M+H]+Calculated for C25H26BrN2O2 +465.1172；Found 465.1167.
Compound nine (3 ai):
1-butyl-2-methoxy-8-methyl-1- (4-phenylbut-1-yn-1-yl) -1,2-dihydro-3H-imidazo [1,5-a ] indol-3-one
1-butyl-2-methoxy-8-methyl-1-(4-phenylbut-1-yn-1-yl)-1,2-dihydro-3H-imidazo[1,5-a]indol-3-one
The reaction mixture was directly subjected to flash chromatography on silica gel (petrol/ethyl acetate: 40/1) to give a pale yellow viscous oil (74.8mg, 75% yield).
1H NMR(600MHz,CDCl3)δ7.82(d,J＝7.7Hz,1H),7.32-7.27(m,2H),7.26-7.20(m,4H),7.08(d,J＝7.3Hz,1H),6.41(d,J＝0.8Hz,1H),4.00(s,3H),2.85(t,J＝7.3Hz,2H),2.60-2.53(m,5H),2.21-2.13(m,1H),2.05-1.98(m,1H),1.39-1.27(m,3H),1.21-1.13(m,1H),0.88(t,J＝7.1Hz,3H)；13C NMR(150MHz,CDCl3)δ151.29,140.29,137.03,132.28,130.89,130.57,128.64,128.47,126.50,124.08,123.66,110.61,97.51,85.16,78.29,65.87,61.11,38.70,34.65,25.80,22.46,20.87,18.81,13.97；HRMS(ESI)m/z:[M+H]+Calculated for C26H29N2O2 +401.2224；Found401.2223.
Compound ten (3 aj):
1-butyl-2,8-dimethoxy-1- (4-phenylbutan-1-yn-1-yl) -1,2-dihydro-3H-imidazo [1,5-a ] indol-3-one 1-butyl-2,8-dimethoxy-1- (4-phenylbut-1-yn-1-yl) -1, 2-dihydro-3H-imidozo [1,5-a ] indol-3-one
The reaction mixture was directly subjected to flash chromatography on silica gel (petrol/ethyl acetate: 40/1) to give a white solid (70.5mg, 68% yield), m.p. (52-54 ℃.
1H NMR(600MHz,CDCl3)δ7.60(d,J＝8.2Hz,1H),7.32-7.28(m,2H),7.27(d,J＝1.5Hz,1H),7.25-7.20(m,3H),6.72(d,J＝8.0Hz,1H),6.55(s,1H),4.00(s,3H),3.98(s,3H),2.84(t,J＝7.3Hz,2H),2.56(t,J＝7.4Hz,2H),2.20-2.12(m,1H),2.04-1.95(m,1H),1.39-1.32(m,1H),1.32-1.27(m,2H),1.22-1.13(m,1H),0.87(t,J＝7.2Hz,3H)；13C NMR(150MHz,CDCl3)δ153.27,151.20,140.29,135.99,131.96,128.62,128.49,126.51,125.07,122.68,106.22,103.53,96.33,85.15,78.15,65.86,61.09,55.54,38.64,34.68,25.77,22.46,20.90,13.96；HRMS(ESI)m/z:[M+H]+Calculated for C26H29N2O3 +417.2173；Found 417.2169.
Compound eleven (3 ak):
1-butyl-2-methoxy-7-methyl-1- (4-phenylbut-1-yn-1-yl) -1,2-dihydro-3H-imidazo [1,5-a ] indol-3-one
1-butyl-2-methoxy-7-methyl-1-(4-phenylbut-1-yn-1-yl)-1,2-dihydro-3H-imidazo[1,5-a]indol-3-one
The reaction mixture was directly subjected to flash chromatography on silica gel (petroleum/ethyl acetate: 40/1) to give a colorless viscous oil (75.7mg, yield 76%).
1H NMR(600MHz,CDCl3)δ7.85(d,J＝8.3Hz,1H),7.38(s,1H),7.31-7.27(m,2H),7.25-7.19(m,3H),7.15(d,J＝8.3Hz,1H),6.31(s,1H),3.99(s,3H),2.84(t,J＝7.3Hz,2H),2.56(t,J＝7.3Hz,2H),2.46(s,3H),2.19-2.09(m,1H),2.04-1.95(m,1H),1.36-1.26(m,3H),1.18-1.10(m,1H),0.86(t,J＝7.1Hz,3H)；13C NMR(150MHz,CDCl3)δ151.29,140.30,137.70,132.89,132.86,129.04,128.63,128.48,126.51,125.40,121.25,112.70,98.72,85.15,78.25,65.87,61.11,38.65,34.67,25.80,22.45,21.70,20.89,13.97；HRMS(ESI)m/z:[M+H]+Calculated for C26H29N2O2 +401.2224；Found 401.2222.
Compound twelve (3 al):
1-butyl-2,7-dimethoxy-1- (4-phenylbutan-1-yn-1-yl) -1,2-dihydro-3H-imidazo [1,5-a ] indol-3-one 1-butyl-2,7-dimethoxy-1- (4-phenylbut-1-yn-1-yl) -1, 2-dihydro-3H-imidozo [1,5-a ] indol-3-one
The reaction mixture was directly subjected to flash chromatography on silica gel (petroleum/ethyl acetate: 20/1) to give a colorless viscous oil (77.6mg, yield 75%).
1H NMR(600MHz,CDCl3)δ7.84(d,J＝8.8Hz,1H),7.31-7.27(m,2H),7.24-7.18(m,3H),7.06(d,J＝2.4Hz,1H),6.95(dd,J＝8.8,2.4Hz,1H),6.31(s,1H),3.98(s,3H),3.86(s,3H),2.83(t,J＝7.3Hz,2H),2.56(t,J＝7.3Hz,2H),2.17-2.10(m,1H),2.02-1.95(m,1H),1.34-1.26(m,3H),1.19-1.11(m,1H),0.86(t,J＝7.1Hz,3H)；13CNMR(150MHz,CDCl3)δ156.48,151.25,140.30,138.44,133.53,128.63,128.49,126.52,125.64,113.73,112.99,104.11,98.93,85.21,78.19,65.88,61.12,55.90,38.63,34.68,25.83,22.46,20.89,13.98；HRMS(ESI)m/z:[M+H]+Calculated for C26H29N2O3 +417.2173；Found 417.2174.
Compound thirteen (3 am):
1-butyl-7-ethoxy-2-methoxy-1- (4-phenylbut-1-yn-1-yl) -1,2-dihydro-3H-imidazo [1,5-a ] indol-3-one
1-butyl-7-ethoxy-2-methoxy-1-(4-phenylbut-1-yn-1-yl)-1,2-dihydro-3H-imidazo[1,5-a]indol-3-one
The reaction mixture was directly subjected to flash chromatography on silica gel (petrol/ethyl acetate: 20/1) to give a white solid (77.5mg, 72% yield), mp 70-72 ℃.
1H NMR(600MHz,CDCl3)δ7.83(d,J＝8.8Hz,1H),7.31-7.26(m,2H),7.25-7.16(m,3H),7.05(d,J＝2.3Hz,1H),6.95(dd,J＝8.8,2.3Hz,1H),6.30(s,1H),4.08(q,J＝7.0Hz,2H),3.98(s,3H),2.83(t,J＝7.3Hz,2H),2.55(t,J＝7.3Hz,2H),2.18-2.08(m,1H),2.02-1.93(m,1H),1.44(t,J＝7.0Hz,3H),1.34-1.25(m,3H),1.19-1.11(m,1H),0.85(t,J＝7.1Hz,3H).13C NMR(150MHz,CDCl3)δ155.78,151.27,140.31,138.37,133.54,128.64,128.49,126.52,125.62,113.71,113.57,105.02,98.94,85.19,78.21,65.88,64.18,61.12,38.63,34.69,25.84,22.47,20.90,15.07,13.99；HRMS(ESI)m/z:[M+H]+Calculated for C27H31N2O3 +431.2329；Found431.2325.
Compound fourteen (3 an):
1-butyl-2-methoxy-6-methyl-1- (4-phenylbut-1-yn-1-yl) -1,2-dihydro-3H-imidazo [1,5-a ] indol-3-one
1-butyl-2-methoxy-6-methyl-1-(4-phenylbut-1-yn-1-yl)-1,2-dihydro-3H-imidazo[1,5-a]indol-3-one
The reaction mixture was directly subjected to flash chromatography on silica gel (petrol/ethyl acetate: 40/1) to give a pale yellow viscous oil (71.6mg, 72% yield).
1H NMR(600MHz,CDCl3)δ7.81(s,1H),7.48(d,J＝8.1Hz,1H),7.32-7.27(m,2H),7.25-7.19(m,3H),7.11(d,J＝8.1Hz,1H),6.35(s,1H),4.00(s,3H),2.85(t,J＝7.3Hz,2H),2.57(t,J＝7.3Hz,2H),2.50(s,3H),2.19-2.12(m,1H),2.04-1.98(m,1H),1.38-1.27(m,3H),1.21-1.13(m,1H),0.87(t,J＝7.1Hz,3H)；13C NMR(150MHz,CDCl3)δ151.29,140.27,136.85,134.17,131.20,130.23,128.60,128.45,126.48,124.84,120.92,113.21,98.87,85.10,78.28,65.83,61.08,38.65,34.65,25.78,22.43,21.73,20.86,13.95；HRMS(ESI)m/z:[M+H]+Calculated for C26H29N2O2 +401.2224；Found 401.2220.
Compound fifteen (3 ao):
1-butyl-2,6-dimethoxy-1- (4-phenylbutan-1-yn-1-yl) -1,2-dihydro-3H-imidazo [1,5-a ] indol-3-one 1-butyl-2,6-dimethoxy-1- (4-phenylbut-1-yn-1-yl) -1, 2-dihydro-3H-imidozo [1,5-a ] indol-3-one
The reaction mixture was directly subjected to flash chromatography on silica gel (petrol/ethyl acetate: 20/1) to give a pale yellow viscous oil (77.6mg, 75% yield).
1H NMR(600MHz,CDCl3)δ7.48(d,J＝2.3Hz,1H),7.45(d,J＝8.7Hz,1H),7.31-7.26(m,2H),7.24-7.18(m,3H),6.91(dd,J＝8.6,2.4Hz,1H),6.31(s,1H),3.99(s,3H),3.88(s,3H),2.83(t,J＝7.3Hz,2H),2.56(t,J＝7.3Hz,2H),2.17-2.09(m,1H),2.02-1.95(m,1H),1.36-1.26(m,3H),1.20-1.13(m,1H),0.86(t,J＝7.1Hz,3H)；13C NMR(150MHz,CDCl3)δ157.61,151.28,140.30,136.03,131.69,128.62,128.48,126.50,126.12,121.89,113.28,98.90,96.54,85.09,78.31,65.86,61.12,55.89,38.69,34.67,25.81,22.45,20.88,13.98；HRMS(ESI)m/z:[M+H]+Calculated for C26H29N2O3 +417.2173；Found 417.2169.
Compound sixteen (3 ap):
methyl 1-butyl-2-methoxy-3-carbonyl-1- (4-phenylbut-1-yn-1-yl) -2, 3-dihydro-1H-imidazo [1,5-a ] indole-7-carboxylate
methyl
1-butyl-2-methoxy-3-oxo-1-(4-phenylbut-1-yn-1-yl)-2,3-dihydro-1H-imidazo[1,5-a]indole-7-carboxylate
The reaction mixture was directly subjected to flash chromatography on silica gel (dichloromethane/ethyl acetate: 100/1) to give a yellow viscous oil (39.9mg, 36% yield).
1H NMR(600MHz,CDCl3)δ8.35(s,1H),8.03(d,J＝8.5Hz,1H),7.99(d,J＝8.5Hz,1H),7.30-7.26(m,2H),7.24-7.17(m,3H),6.44(s,1H),3.99(s,3H),3.95(s,3H),2.83(t,J＝7.3Hz,2H),2.56(t,J＝7.3Hz,2H),2.18-2.12(m,1H),2.03-1.97(m,1H),1.35-1.26(m,3H),1.17-1.08(m,1H),0.85(t,J＝7.1Hz,3H)；13C NMR(150MHz,CDCl3)δ167.53,150.48,140.20,138.72,133.37,132.27,128.63,128.52,126.58,125.38,125.30,123.93,112.75,99.55,85.69,77.78,65.96,61.12,52.27,38.62,34.59,25.78,22.41,20.85,13.96；HRMS(ESI)m/z:[M+H]+Calculated for C27H29N2O4 +445.2122；Found 445.2116.
Compound seventeen (3 aq):
1-butyl-2-methoxy-9-methyl-1- (4-phenylbut-1-yn-1-yl) -1,2-dihydro-3H-imidazo [1,5-a ] indol-3-one
1-butyl-2-methoxy-9-methyl-1-(4-phenylbut-1-yn-1-yl)-1,2-dihydro-3H-imidazo[1,5-a]indol-3-one
The reaction mixture was directly subjected to flash chromatography on silica gel (petroleum/ethyl acetate: 30/1) to give a colorless viscous oil (70.6mg, yield 71%).
1H NMR(600MHz,CDCl3)δ7.95(d,J＝8.0Hz,1H),7.54(d,J＝7.7Hz,1H),7.35-7.32(m,1H),7.31-7.26(m,3H),7.24-7.20(m,3H),4.00(s,3H),2.86(t,J＝7.3Hz,2H),2.60(t,J＝7.3Hz,2H),2.25(s,3H),2.22-2.15(m,1H),2.15-2.08(m,1H),1.33-1.23(m,3H),1.11-1.03(m,1H),0.85(t,J＝7.2Hz,3H)；13C NMR(150MHz,CDCl3)δ151.39,140.24,133.76,131.74,130.67,128.53,128.50,126.51,124.01,122.87,119.29,113.04,108.79,85.09,77.64,65.84,60.79,38.35,34.72,25.96,22.42,20.77,13.97,8.13；HRMS(ESI)m/z:[M+H]+Calculated for C26H29N2O2 +401.2224；Found401.2220.
Compound eighteen (3 ar):
9-benzyl-1-butyl-2-methoxy-1- (4-phenylbut-1-yn-1-yl) -1,2-dihydro-3H-imidazo [1,5-a ] indol-3-one
9-benzyl-1-butyl-2-methoxy-1-(4-phenylbut-1-yn-1-yl)-1,2-dihydro-3H-imidazo[1,5-a]indol-3-one
The reaction mixture was directly subjected to flash chromatography on silica gel (petroleum/ethyl acetate: 25/1) to give a colorless viscous oil (86.3mg, yield 72%).
1H NMR(600MHz,CDCl3)δ7.99(d,J＝8.1Hz,1H),7.40(d,J＝7.9Hz,1H),7.35-7.30(m,1H),7.30-7.26(m,4H),7.25-7.17(m,7H),4.18(d,J＝16.1Hz,1H),4.05(d,J＝16.1Hz,1H),4.01(s,3H),2.78(t,J＝7.4Hz,2H),2.53(t,J＝7.4Hz,2H),2.23-2.16(m,1H),2.03-1.96(m,1H),1.24-1.16(m,2H),1.16-1.09(m,1H),0.93-0.84(m,1H),0.77(t,J＝7.1Hz,3H)；13C NMR(150MHz,CDCl3)δ151.28,140.20,139.75,133.05,132.82,130.87,128.50,128.49,128.49,128.46,126.51,126.32,124.05,123.04,120.10,113.09,111.69,85.25,77.90,65.87,60.72,38.39,34.55,29.48,25.68,22.24,20.69,13.86；HRMS(ESI)m/z:[M+H]+Calculated for C32H33N2O2 +477.2537；Found 477.2532.
Compound nineteen (3 as):
ethyl 2- (1-butyl-2-methoxy-3-carbonyl-1- (4-phenylbut-1-yn-1-yl) -2, 3-dihydro-1H-imidazo [1,5-a ] indol-9-yl) acetate
ethyl
2-(1-butyl-2-methoxy-3-oxo-1-(4-phenylbut-1-yn-1-yl)-2,3-dihydro-1H-imidazo[1,5-a]indol-9-yl)acetate
The reaction mixture was directly subjected to flash chromatography on silica gel (petroleum/ethyl acetate: 25/1) to give a yellow viscous oil (64.5mg, 55% yield).
1H NMR(600MHz,CDCl3)δ7.95(d,J＝8.1Hz,1H),7.60(d,J＝7.9Hz,1H),7.36-7.32(m,1H),7.31-7.26(m,3H),7.24-7.19(m,3H),4.18-4.11(m,2H),3.98(s,3H),3.73-3.63(m,2H),2.85(t,J＝7.3Hz,2H),2.59(t,J＝7.3Hz,2H),2.26-2.13(m,2H),1.29-1.25(m,2H),1.23(t,J＝7.1Hz,3H),1.21-1.14(m,1H),1.01-0.91(m,1H),0.82(t,J＝7.3Hz,3H)；13C NMR(150MHz,CDCl3)δ170.52,151.11,140.16,133.65,132.58,130.72,128.54,128.54,126.57,124.28,123.24,119.89,113.10,105.98,85.38,77.47,65.91,61.15,60.57,38.79,34.58,29.94,25.63,22.35,20.73,14.32,13.94；HRMS(ESI)m/z:[M+H]+Calculated for C29H33N2O4 +473.2435；Found473.2431.
Compound twenty (3 at):
1-butyl-2-ethoxy-1- (4-phenylbut-1-yn-1-yl) -1,2-dihydro-3H-imidazo [1,5-a ] indol-3-one
1-butyl-2-ethoxy-1-(4-phenylbut-1-yn-1-yl)-1,2-dihydro-3H-imidazo[1,5-a]indol-3-one
The reaction mixture was directly subjected to flash chromatography on silica gel (petroleum/ethyl acetate: 40/1) to give a colorless viscous oil (85.9mg, yield 86%).
1H NMR(600MHz,CDCl3)δ7.97(d,J＝8.1Hz,1H),7.60(dd,J＝8.0,1.0Hz,1H),7.35-7.31(m,1H),7.32-7.25(m,4H),7.25-7.18(m,3H),6.38(s,1H),4.27-4.17(m,2H),2.83(t,J＝7.3Hz,2H),2.56(t,J＝7.4Hz,2H),2.20-2.11(m,1H),2.02-1.95(m,1H),1.36(t,J＝7.1Hz,3H),1.32-1.26(m,3H),1.19-1.10(m,1H),0.85(t,J＝7.2Hz,3H)；13C NMR(150MHz,CDCl3)δ151.53,140.30,137.79,132.57,130.87,128.62,128.50,126.53,123.94,123.25,121.37,113.14,98.98,85.15,78.35,73.67,61.26,38.69,34.67,25.79,22.46,20.85,14.14,13.98；HRMS(ESI)m/z:[M+H]+Calculated for C26H29N2O2 +401.2224；Found 401.2220.
Compound twenty one (3 au):
1-butyl-2-isopropoxy-1- (4-phenylbut-1-yn-1-yl) -1,2-dihydro-3H-imidazo [1,5-a ] indol-3-one
1-butyl-2-isopropoxy-1-(4-phenylbut-1-yn-1-yl)-1,2-dihydro-3H-imidazo[1,5-a]indol-3-one
The reaction mixture was directly subjected to flash chromatography on silica gel (petrol/ethyl acetate: 40/1) to give a pale yellow viscous oil (38.3mg, 37% yield).
1H NMR(600MHz,CDCl3)δ7.97(d,J＝8.1Hz,1H),7.60(d,J＝7.8Hz,1H),7.35-7.26(m,4H),7.25-7.18(m,3H),6.38(s,1H),4.48-4.38(m,1H),2.83(t,J＝7.3Hz,2H),2.56(t,J＝7.3Hz,2H),2.18-2.10(m,1H),2.02-1.91(m,1H),1.37(d,J＝6.1Hz,3H),1.32(d,J＝6.3Hz,3H),1.31-1.22(m,3H),1.17-1.08(m,1H),0.85(t,J＝7.1Hz,3H)；13C NMR(150MHz,CDCl3)δ152.21,140.31,138.02,132.65,130.85,128.59,128.52,126.54,123.90,123.25,121.34,113.18,99.02,85.16,79.51,78.60,61.61,38.74,34.67,25.77,22.45,21.36,21.33,20.80,13.96；HRMS(ESI)m/z:[M+H]+Calculated for C27H31N2O2 +415.2380；Found 415.2375.
Compound twenty-two (3 aw):
1- (benzyloxy) -1-butyl-1- (4-phenylbut-1-yn-1-yl) -1,2-dihydro-3H-imidazo [1,5-a ] indol-3-one
1-(benzyloxy)-1-butyl-1-(4-phenylbut-1-yn-1-yl)-1,2-dihydro-3H-imidazo[1,5-a]indol-3-one
The reaction mixture was directly subjected to flash chromatography on silica gel (petroleum/ethyl acetate: 40/1) to give a colorless viscous oil (76.8mg, yield 66%).
1H NMR(600MHz,CDCl3)δ7.99(d,J＝8.1Hz,1H),7.61(d,J＝7.8Hz,1H),7.52(d,J＝6.1Hz,2H),7.46-7.37(m,3H),7.36-7.32(m,1H),7.31-7.26(m,3H),7.25-7.17(m,3H),6.40(s,1H),5.26-5.16(m,2H),2.84(t,J＝7.3Hz,2H),2.55(t,J＝7.3Hz,2H),2.17-2.09(m,1H),2.00-1.90(m,1H),1.36-1.29(m,1H),1.29-1.22(m,2H),1.20-1.12(m,1H),0.84(t,J＝7.2Hz,3H)；13C NMR(150MHz,CDCl3)δ151.40,140.29,137.75,135.44,132.60,130.87,129.67,128.86,128.61,128.54,128.51,126.54,123.99,123.31,121.40,113.15,99.08,85.41,80.01,78.18,61.42,38.74,34.67,25.80,22.44,20.91,13.95；HRMS(ESI)m/z:[M+H]+Calculated for C31H31N2O2 +463.2380；Found 463.2383.
Compound twenty three (3 ax):
2-methoxy-1-phenethyl-1- (4-phenylbut-1-yn-1-yl) -1,2-dihydro-3H-imidazo [1,5-a ] indol-3-one
2-methoxy-1-phenethyl-1-(4-phenylbut-1-yn-1-yl)-1,2-dihydro-3H-imidazo[1,5-a]indol-3-one
The reaction mixture was directly subjected to flash chromatography on silica gel (petroleum/ethyl acetate: 40/1) to give a pale yellow viscous oil (82.9mg, 76% yield).
1H NMR(600MHz,CDCl3)δ8.02(d,J＝8.1Hz,1H),7.64(d,J＝7.9Hz,1H),7.40-7.34(m,1H),7.33-7.26(m,5H),7.25-7.21(m,3H),7.21-7.17(m,1H),7.15-7.09(m,2H),6.46(s,1H),4.04(s,3H),2.86(t,J＝7.3Hz,2H),2.75-2.68(m,1H),2.60(t,J＝7.3Hz,2H),2.57-2.52(m,1H),2.52-2.46(m,1H),2.38-2.28(m,1H)；13C NMR(150MHz,CDCl3)δ151.15,140.48,140.21,137.18,132.57,130.91,128.61,128.56,128.52,128.44,126.55,126.26,124.18,123.43,121.51,113.18,99.30,85.86,77.73,65.98,60.93,40.66,34.62,30.31,20.86；HRMS(ESI)m/z:[M+H]+Calculated for C29H27N2O2 +435.2067；Found 435.2066.
Compound twenty-four (3 ay):
1- ((benzyloxy) methyl) -2-methoxy-1- (4-phenylbut-1-yn-1-yl) -1,2-dihydro-3H-imidazo [1,5-a ] indol-3-one
1-((benzyloxy)methyl)-2-methoxy-1-(4-phenylbut-1-yn-1-yl)-1,2-dihydro-3H-imidazo[1,5-a]indol-3-one
The reaction mixture was directly subjected to flash chromatography on silica gel (petrol/ethyl acetate: 20/1) to give a pale yellow viscous oil (42.7mg, 38% yield).
1H NMR(600MHz,CDCl3)δ7.99(d,J＝8.2Hz,1H),7.60(d,J＝7.9Hz,1H),7.36-7.31(m,1H),7.29-7.26(m,3H),7.25-7.18(m,6H),7.13-7.08(m,2H),6.40(s,1H),4.50(d,J＝12.4Hz,1H),4.40(d,J＝12.4Hz,1H),4.03(d,J＝10.1Hz,1H),3.97(s,3H),3.75(d,J＝10.1Hz,1H),2.83(t,J＝7.3Hz,2H),2.56(t,J＝7.3Hz,2H)；13C NMR(150MHz,CDCl3)δ151.90,140.12,137.48,135.99,132.55,131.09,128.61,128.53,128.38,127.78,127.66,126.58,124.03,123.20,121.51,113.10,99.09,86.79,75.21,73.55,72.05,65.95,61.06,34.53,20.92；HRMS(ESI)m/z:[M+H]+Calculated for C29H27N2O3 +451.2016；Found 451.2018.
Compound twenty five (3 az):
1- (3-hydroxypropyl) -2-methoxy-1- (4-phenylbut-1-yn-1-yl) -1,2-dihydro-3H-imidazo [1,5-a ] indol-3-one
1-(3-hydroxypropyl)-2-methoxy-1-(4-phenylbut-1-yn-1-yl)-1,2-dihydro-3H-imidazo[1,5-a]indol-3-one
The reaction mixture was directly subjected to flash chromatography on silica gel (dichloromethane/ethyl acetate: 80/1) to give a pale yellow viscous oil (63.5mg, 65% yield).
1H NMR(600MHz,CDCl3)δ7.96(d,J＝8.0Hz,1H),7.59(d,J＝7.8Hz,1H),7.34-7.31(m,1H),7.30-7.25(m,3H),7.24-7.18(m,3H),6.40(s,1H),3.99(s,3H),3.60(t,J＝6.3Hz,2H),2.83(t,J＝7.3Hz,2H),2.56(t,J＝7.3Hz,2H),2.30-2.23(m,1H),2.11-2.05(m,1H),1.69(s,1H),1.65-1.57(m,1H),1.49-1.42(m,1H)；13C NMR(150MHz,CDCl3)δ151.13,140.25,137.24,132.52,130.85,128.63,128.51,126.52,124.15,123.41,121.47,113.13,99.25,85.67,77.79,65.95,62.16,60.88,35.40,34.59,27.18,20.81；HRMS(ESI)m/z:[M+H]+Calculated for C24H25N2O3 +389.1860；Found 389.1861.
Compound twenty-six (3 ba):
2-methoxy-1- (3- ((4-methoxybenzyl) oxo) propyl) -1- (4-phenylbut-1-yn-1-yl) -1,2-dihydro-3H-imidazo [1,5-a ] indol-3-one
2-methoxy-1-(3-((4-methoxybenzyl)oxy)propyl)-1-(4-phenylbut-1-yn-1-yl)-1,2-dihydro-3H-imidazo[1,5-a]indol-3-one
The reaction mixture was directly subjected to flash chromatography on silica gel (petroleum/ethyl acetate: 20/1) to give a yellow viscous oil (92.0mg, 72% yield).
1H NMR(600MHz,CDCl3)δ7.96(d,J＝8.1Hz,1H),7.58(d,J＝7.9Hz,1H),7.35-7.30(m,1H),7.29-7.24(m,3H),7.24-7.16(m,5H),6.86(d,J＝8.6Hz,2H),6.38(s,1H),4.38(s,2H),3.98(s,3H),3.80(s,3H),3.48-3.32(m,2H),2.82(t,J＝7.3Hz,2H),2.54(t,J＝7.3Hz,2H),2.35-2.21(m,1H),2.10-2.01(m,1H),1.72-1.64(m,1H),1.58-1.49(m,1H)；13C NMR(150MHz,CDCl3)δ159.29,151.13,140.28,137.32,132.56,130.90,130.52,129.36,128.63,128.51,126.52,124.10,123.36,121.45,113.89,113.15,99.24,85.62,77.84,72.65,69.25,65.92,60.97,55.40,35.76,34.66,24.41,20.90；HRMS(ESI)m/z:[M+H]+Calculated for C32H33N2O4 +509.2435；Found 509.2437.
Compound twenty-seven (3 bb):
2-methoxy-1- (4-phenylbut-1-yn-1-yl) -1- (3- ((tetrahydro-2H-pyran-2-yl) oxo) propyl) -1,2-dihydro-3H-imidazo [1,5-a ] indol-3-one
2-methoxy-1-(4-phenylbut-1-yn-1-yl)-1-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-1,2-dihydro-3H-imidazo[1,5-a]indol-3-one
The reaction mixture was directly subjected to flash chromatography on silica gel (petroleum/ethyl acetate: 10/1) to give a pale yellow viscous oil (80.9mg, yield 68%).
1H NMR(600MHz,CDCl3)δ7.96(d,J＝8.1Hz,1H),7.59(d,J＝7.9Hz,1H),7.35-7.30(m,1H),7.30-7.25(m,3H),7.24-7.16(m,3H),6.40(s,1H),4.58-4.47(m,1H),3.99(s,3H),3.80(t,J＝9.5Hz,1H),3.76-3.67(m,1H),3.51-3.43(m,1H),3.39-3.30(m,1H),2.83(t,J＝7.3Hz,2H),2.55(t,J＝7.3Hz,2H),2.33-2.22(m,1H),2.13-2.04(m,1H),1.84-1.75(m,1H),1.73-1.64(m,2H),1.60-1.45(m,5H)；13C NMR(150MHz,CDCl3)δ151.15,140.27,137.32,132.58,130.91,128.63,128.50,126.52,124.10,123.37,121.45,113.15,99.23,98.93,98.85,85.62,77.87,66.73,65.91,62.45,62.37,61.00,35.76,35.73,34.65,30.76,30.74,25.54,24.42,20.92,19.69,19.63；HRMS(ESI)m/z:[M+Na]+Calculated for C29H32N2O4Na+495.2254；Found495.2254.
Compound dioctadecyl (3 bc):
1- (3-chloropropyl) -2-methoxy-1- (4-phenylbut-1-yn-1-yl) -1,2-dihydro-3H-imidazo [1,5-a ] indol-3-one
1-(3-chloropropyl)-2-methoxy-1-(4-phenylbut-1-yn-1-yl)-1,2-dihydro-3H-imidazo[1,5-a]indol-3-one
The reaction mixture was directly subjected to flash chromatography on silica gel (petroleum/ethyl acetate: 40/1) to give a yellow viscous oil (63.8mg, yield 63%).
1H NMR(600MHz,CDCl3)δ7.98(d,J＝8.1Hz,1H),7.61(d,J＝7.9Hz,1H),7.37-7.32(m,1H),7.31-7.27(m,3H),7.25-7.19(m,3H),6.40(s,1H),4.00(s,3H),3.50(t,J＝6.4Hz,2H),2.84(t,J＝7.3Hz,2H),2.58(t,J＝7.3Hz,2H),2.39-2.31(m,1H),2.19-2.10(m,1H),1.90-1.82(m,1H),1.74-1.65(m,1H)；13C NMR(150MHz,Chloroform-d)δ151.03,140.16,136.92,132.48,130.87,128.62,128.51,126.55,124.26,123.48,121.52,113.15,99.34,85.99,77.52,65.96,60.54,44.33,36.38,34.53,27.12,20.82；HRMS(ESI)m/z:[M+H]+Calculated for C24H24ClN2O2 +407.1521；Found 407.1526.
Compound twenty-nine (3 bd):
1- (but-1-yn-1-yl) -1-butyl-2-methoxy-1,2-dihydro-3H-imidazo [1,5-a ] indol-3-one
1- (but-1-yn-1-yl) -1-butyl-2-methoxy-1, 2-dihydro-3H-imidozo [1,5-a ] indol-3-one the reaction mixture was purified by flash chromatography directly on silica gel (petrol/ethyl acetate: 40/1) to give a yellow viscous oil (54.6mg, 70% yield).
1H NMR(600MHz,CDCl3)δ7.97(dd,J＝8.1,1.0Hz,1H),7.59(d,J＝7.9Hz,1H),7.35-7.29(m,1H),7.28-7.23(m,1H),6.45(s,1H),4.10(s,3H),2.26(q,J＝7.5Hz,2H),2.23-2.17(m,1H),2.09-2.02(m,1H),1.41-1.35(m,1H),1.34-1.28(m,2H),1.25-1.18(m,1H),1.16(t,J＝7.5Hz,3H),0.87(t,J＝7.2Hz,3H)；13C NMR(150MHz,CDCl3)δ151.14,137.78,132.57,130.88,123.96,123.27,121.40,113.12,98.91,87.34,76.62,65.95,61.15,38.76,25.84,22.45,13.97,13.62,12.53；HRMS(ESI)m/z:[M+H]+Calculated for C19H23N2O2 +311.1754；Found 311.1754.
Compound thirty (3 be):
1-butyl-1- (cyclohexylethynyl) -2-methoxy-1,2-dihydro-3H-imidazo [1,5-a ] indol-3-one
1-butyl-1-(cyclohexylethynyl)-2-methoxy-1,2-dihydro-3H-imidazo[1,5-a]indol-3-one
The reaction mixture was directly subjected to flash chromatography on silica gel (petrol/ethyl acetate: 40/1) to give a pale yellow solid (77.4mg, 85% yield), mp 50-52 ℃.
1H NMR(600MHz,CDCl3)δ7.97(dd,J＝8.1,1.0Hz,1H),7.59(d,J＝7.8Hz,1H),7.34-7.29(m,1H),7.28-7.23(m,1H),6.45(s,1H),4.10(s,3H),2.49-2.41(m,1H),2.25-2.17(m,1H),2.08-1.99(m,1H),1.83-1.74(m,2H),1.72-1.63(m,2H),1.54-1.41(m,3H),1.40-1.29(m,6H),1.25-1.16(m,1H),0.86(t,J＝7.2Hz,3H)；13CNMR(150MHz,CDCl3)δ151.05,137.95,132.58,130.89,123.92,123.24,121.38,113.13,98.91,90.02,65.95,61.11,38.92,32.38,32.36,28.99,25.90,25.88,24.75,22.45,14.00；HRMS(ESI)m/z:[M+H]+Calculated for C23H29N2O2 +365.2224；Found 365.2228.
Compound thirty-one (3 bf):
1-butyl-2-methoxy-1- (phenylethynyl) -1,2-dihydro-3H-imidazo [1,5-a ] indol-3-one
1-butyl-2-methoxy-1-(phenylethynyl)-1,2-dihydro-3H-imidazo[1,5-a]indol-3-one
The reaction mixture was directly subjected to flash chromatography on silica gel (petrol/ethyl acetate: 40/1) to give a pale yellow solid (69.8mg, 78% yield), mp 102-.
1H NMR(600MHz,CDCl3)δ8.01(d,J＝8.1Hz,1H),7.62(d,J＝7.9Hz,1H),7.49-7.43(m,2H),7.38-7.31(m,4H),7.30-7.27(m,1H),6.54(s,1H),4.15(s,3H),2.39-2.31(m,1H),2.22-2.15(m,1H),1.50-1.42(m,1H),1.37(h,J＝7.1Hz,2H),1.33-1.25(m,1H),0.90(t,J＝7.2Hz,3H)；13C NMR(150MHz,CDCl3)δ151.11,137.09,132.57,131.97,130.95,129.11,128.51,124.16,123.41,121.89,121.50,113.19,99.40,85.92,85.06,66.10,61.47,38.56,25.87,22.48,14.01；HRMS(ESI)m/z:[M+H]+Calculated for C23H23N2O2 +359.1754；Found 359.1757.
Compound thirty-two (3 bg):
1-butyl-1- (5-hydroxypent-1-yn-1-yl) -2-methoxy-1,2-dihydro-3H-imidazo [1,5-a ] indol-3-one
1-butyl-1-(5-hydroxypent-1-yn-1-yl)-2-methoxy-1,2-dihydro-3H-imidazo[1,5-a]indol-3-one
The reaction mixture was directly subjected to flash chromatography on silica gel (petrol/ethyl acetate: 3/1) to give a pale yellow viscous oil (55.7mg, 65% yield).
1H NMR(600MHz,CDCl3)δ7.96(dd,J＝8.2,1.0Hz,1H),7.62-7.56(m,1H),7.35-7.29(m,1H),7.29-7.22(m,1H),6.44(d,J＝0.5Hz,1H),4.08(s,3H),3.73(t,J＝6.1Hz,2H),2.37(t,J＝7.0Hz,2H),2.23-2.16(m,1H),2.08-2.02(m,1H),1.81-1.75(m,2H),1.73(s,1H),1.41-1.34(m,1H),1.34-1.27(m,2H),1.24-1.16(m,1H),0.86(t,J＝7.2Hz,3H)；13C NMR(150MHz,CDCl3)δ151.31,137.58,132.57,130.85,124.06,123.35,121.45,113.13,98.97,85.38,77.74,65.98,61.63,61.23,38.70,31.15,25.87,22.44,15.42,13.97；HRMS(ESI)m/z:[M+H]+Calculated for C20H25N2O3 +341.1860；Found 341.1861.
Compound thirty-three (3 bh):
5- (1-butyl-2-methoxy-3-carbonyl-2, 3-dihydro-1H-imidazo [1,5-a ] indol-1-yl) pent-4-yn-1-yl acetate
5-(1-butyl-2-methoxy-3-oxo-2,3-dihydro-1H-imidazo[1,5-a]indol-1-yl)pent-4-yn-1-yl acetate
The reaction mixture was directly subjected to flash chromatography on silica gel (petroleum/ethyl acetate: 16/1) to give a pale yellow viscous oil (76.6mg, yield 80%).
1H NMR(600MHz,CDCl3)δ7.96(d,J＝8.1Hz,1H),7.59(d,J＝7.8Hz,1H),7.34-7.29(m,1H),7.28-7.23(m,1H),6.45(s,1H),4.15(t,J＝6.3Hz,2H),4.08(s,3H),2.35(t,J＝7.1Hz,2H),2.22-2.16(m,1H),2.09-2.01(m,4H),1.85(p,J＝6.7Hz,2H),1.41-1.34(m,1H),1.31(h,J＝7.0Hz,2H),1.23-1.14(m,1H),0.86(t,J＝7.2Hz,3H)；13C NMR(150MHz,CDCl3)δ171.05,151.22,137.52,132.55,130.85,124.03,123.32,121.44,113.11,98.99,84.50,78.07,65.95,63.00,61.13,38.67,27.55,25.84,22.42,20.99,15.60,13.94；HRMS(ESI)m/z:[M+H]+Calculated for C22H27N2O4 +383.1965；Found 383.1965.
Compound thirty-four (3 bi):
2- (5- (1-butyl-2-methoxy-3-carbonyl-2, 3-dihydro-1H-imidazo [1,5-a ] indol-1-yl) pent-4-yn-1-yl) isoindoline-1, 3-dione
2-(5-(1-butyl-2-methoxy-3-oxo-2,3-dihydro-1H-imidazo[1,5-a]indol-1-yl)pent-4-yn-1-yl)isoindoline-1,3-dione
The reaction mixture was directly subjected to flash chromatography on silica gel (petrol/ethyl acetate: 4/1) to give a pale yellow viscous oil (84.7mg, 72% yield).
1H NMR(600MHz,CDCl3)δ7.92(d,J＝8.2Hz,1H),7.71-7.65(m,2H),7.59(d,J＝7.8Hz,1H),7.56-7.50(m,2H),7.34-7.29(m,1H),7.26(d,J＝14.9Hz,1H),6.42(s,1H),4.07(s,3H),3.78(t,J＝6.9Hz,2H),2.37(t,J＝6.8Hz,2H),2.16-2.07(m,1H),1.99-1.90(m,3H),1.32-1.22(m,3H),1.15-1.07(m,1H),0.82(t,J＝7.1Hz,3H)；13C NMR(150MHz,CDCl3)δ168.46,151.04,137.43,133.93,132.61,131.99,130.88,123.93,123.28,123.13,121.49,113.17,99.07,84.68,77.89,66.03,60.94,38.79,37.44,27.08,25.73,22.39,16.81,13.94；HRMS(ESI)m/z:[M+H]+Calculated for C28H28N3O4 +470.2074；Found 470.2070.
Compound thirty-five (3 bj):
1- (hex-1-yn-1-yl) -2-methoxy-1-phenylethyl-1, 2-dihydro-3H-imidazo [1,5-a ] indol-3-one
1-(hex-1-yn-1-yl)-2-methoxy-1-phenethyl-1,2-dihydro-3H-imidazo[1,5-a]indol-3-one
The reaction mixture was directly subjected to flash chromatography on silica gel (petrol/ethyl acetate: 40/1) to give a yellow viscous solid (63.0mg, 65% yield), mp 38-40 ℃.
1H NMR(600MHz,CDCl3)δ8.05-8.00(m,1H),7.67-7.61(m,1H),7.39-7.35(m,1H),7.32-7.29(m,1H),7.29-7.25(m,2H),7.21-7.18(m,1H),7.17-7.14(m,2H),6.53(d,J＝0.8Hz,1H),4.15(s,3H),2.80-2.73(m,1H),2.64-2.57(m,1H),2.57-2.51(m,1H),2.42-2.35(m,1H),2.29(t,J＝7.0Hz,2H),1.58-1.52(m,2H),1.49-1.42(m,2H),0.95(t,J＝7.3Hz,3H)；13C NMR(150MHz,CDCl3)δ151.15,140.53,137.38,132.59,130.94,128.58,128.47,126.27,124.15,123.39,121.51,113.18,99.20,86.75,76.81,66.04,60.99,40.94,30.49,30.41,22.03,18.49,13.67；HRMS(ESI)m/z:[M+H]+Calculated for C25H27N2O2 +387.2067；Found 387.2063.
Compound thirty-six (3 bk):
n- (2- (1-butyl-2, 7-dimethoxy-3-carbonyl-1- (4-phenylbut-1-yn-1-yl) -2, 3-dihydro-1H-imidazo [1,5-a ] indol-9-yl) ethyl) acetamide
N-(2-(1-butyl-2,7-dimethoxy-3-oxo-1-(4-phenylbut-1-yn-1-yl)-2,3-dihydro-1H-imidazo[1,5-a]indol-9-yl)ethyl)acetamide
The reaction mixture was directly subjected to flash chromatography on silica gel (dichloromethane/ethyl acetate: 20/1) to give a pale yellow viscous oil (88.9mg, 71% yield).
1H NMR(600MHz,CDCl3)δ7.82(d,J＝8.8Hz,1H),7.30-7.25(m,2H),7.23-7.18(m,3H),7.06(d,J＝2.2Hz,1H),6.94(dd,J＝8.8,2.4Hz,1H),5.66(s,1H),3.96(s,3H),3.85(s,3H),3.54-3.39(m,2H),2.94-2.87(m,1H),2.87-2.78(m,3H),2.59(t,J＝7.2Hz,2H),2.24-2.16(m,1H),2.13-2.06(m,1H),1.92(s,3H),1.30-1.22(m,2H),1.22-1.14(m,1H),0.95-0.87(m,1H),0.82(t,J＝7.2Hz,3H)；13C NMR(150MHz,CDCl3)δ170.26,156.52,151.28,140.14,133.75,133.67,128.59,128.52,126.55,125.40,113.85,113.29,109.86,102.38,85.42,78.42,65.87,60.69,55.93,39.39,38.56,34.49,25.75,23.78,23.40,22.34,20.75,13.93；HRMS(ESI)m/z:[M+H]+Calculated for C30H36N3O4 +502.2700；Found 502.2696.
Compound thirty-seven (3 bl):
1-butyl-2-methoxy-1- (4-phenylbut-1-yn-1-yl) -1, 2-dihydro-3H-pyrrolo [1,2-c ] imidazol-3-one
1-butyl-2-methoxy-1-(4-phenylbut-1-yn-1-yl)-1,2-dihydro-3H-pyrrolo[1,2-c]imidazol-3-one
The reaction mixture was directly subjected to flash chromatography on silica gel (petrol/ethyl acetate: 25/1) to give a pale yellow viscous oil (54.9mg, 65% yield).
1H NMR(600MHz,CDCl3)δ7.31-7.27(m,2H),7.22(d,J＝7.4Hz,1H),7.20(d,J＝6.8Hz,2H),7.05(dd,J＝3.4,0.8Hz,1H),6.41-6.37(m,1H),6.05(d,J＝3.1Hz,1H),3.96(s,3H),2.82(t,J＝7.3Hz,2H),2.54(t,J＝7.3Hz,2H),2.12-2.04(m,1H),1.94-1.88(m,1H),1.31-1.21(m,3H),1.10-1.01(m,1H),0.85(t,J＝7.2Hz,3H)；13CNMR(150MHz,CDCl3)δ150.45,140.31,132.87,128.60,128.47,126.49,115.50,112.45,103.42,84.78,78.27,65.72,61.03,38.97,34.66,25.70,22.38,20.87,13.97；HRMS(ESI)m/z:[M+H]+Calculated for C21H25N2O2 +337.1911；Found 337.1909.
Compound thirty-eight (3 bm):
1-butyl-2-methoxy-5-methyl-1- (4-phenylbut-1-yn-1-yl) -1, 2-dihydro-3H-pyrrolo [1,2-c ] imidazol-3-one
1-butyl-2-methoxy-5-methyl-1-(4-phenylbut-1-yn-1-yl)-1,2-dihydro-3H-pyrrolo[1,2-c]imidazol-3-one
The reaction mixture was directly subjected to flash chromatography on silica gel (petrol/ethyl acetate: 25/1) to give a pale yellow viscous oil (57.6mg, 66% yield).
1H NMR(600MHz,CDCl3)δ7.33-7.27(m,2H),7.25-7.17(m,3H),6.01(dd,J＝3.1,1.1Hz,1H),5.90(d,J＝3.1Hz,1H),3.95(s,3H),2.82(t,J＝7.3Hz,2H),2.53(t,J＝7.4Hz,2H),2.45(s,3H),2.08-2.02(m,1H),1.91-1.84(m,1H),1.30-1.22(m,3H),1.16-1.08(m,1H),0.87(t,J＝7.1Hz,3H)；13C NMR(150MHz,CDCl3)δ151.32,140.39,131.61,128.61,128.46,126.47,125.67,113.26,102.68,84.44,78.67,65.64,60.45,38.97,34.73,25.75,22.44,20.90,14.00,11.52；HRMS(ESI)m/z:[M+H]+Calculated for C22H27N2O2 +351.2067；Found 351.2066.
Claims (8)
1. A method for preparing an alkynylated imidazo [1,5-a ] indole compound, wherein the structural formula of the alkynylated imidazo [1,5-a ] indole compound is as shown in formula < III >, and the preparation method comprises the following steps:
in the formula<Ⅰ>Indole compounds and compounds of formula<Ⅱ>The alpha, alpha-difluoromethylene alkyne compound is used as a substrate and takes [ Cp RhCl2]2Is taken as a catalyst, potassium fluoride is taken as an additive, methanol is taken as a solvent, and the reaction is carried out for 9 to 30 hours at the temperature of 60 ℃ to obtain the formula<Ⅲ>A compound shown as the formula (I);
wherein R is1Represents a substituent at any position on the phenyl ring selected from the group consisting of: hydrogen, halogen, alkyl, alkoxy, ester groups;
R2selected from the following groups: hydrogen, substituted or unsubstituted alkyl;
R3selected from the following groups: substituted or unsubstituted alkyl;
R4selected from the following groups: substituted or unsubstituted alkyl;
R5selected from the following groups: substituted or unsubstituted alkyl, aryl;
the substitution means that one or more hydrogen atoms on the group are substituted with a substituent selected from the group consisting of: phenyl, ester, acetamido, benzyloxy, hydroxy, p-methoxybenzyloxy, tetrahydro-2H-pyran-2-yl) oxy, halogen, acetoxy, 1, 3-dicarbonylisoindolin-2-yl.
2. The method of claim 1, wherein the halogen comprises F, Cl, Br, or I.
3. The method of claim 1, wherein the alkyl group comprises a methyl group, an ethyl group, an isopropyl group, a n-butyl group, or a cyclohexyl group, and the alkoxy group comprises a methoxy group or an ethoxy group; the aryl group includes phenyl.
4. The process of claim 1, wherein the molar ratio of compound i to compound ii is 1: 1.3.
5. The process according to claim 4, wherein the catalyst is used in an amount of 1 to 10%, preferably 5%, based on the molar amount of compound I.
6. The process according to claim 1, wherein the molar ratio of additive to compound i is 1:1.
7. An alkynylated imidazo [1,5-a ] indole compound of formula (III) prepared by the process of any one of claims 1 to 6.
8. The alkynylated imidazo [1,5-a ] indole compound of claim 7, wherein compound iii comprises a compound having any one of the following structures:
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