CN102250021A - Method for preparing quinoxaline compounds and benzimidazole compounds - Google Patents

Method for preparing quinoxaline compounds and benzimidazole compounds Download PDF

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CN102250021A
CN102250021A CN2011101067024A CN201110106702A CN102250021A CN 102250021 A CN102250021 A CN 102250021A CN 2011101067024 A CN2011101067024 A CN 2011101067024A CN 201110106702 A CN201110106702 A CN 201110106702A CN 102250021 A CN102250021 A CN 102250021A
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cilin
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quinoline
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CN102250021B (en
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崔冬梅
庄丹闻
陈颖
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Huzhou You Yan Intellectual Property Service Co ltd
Tekang Pharmaceutical Group Co ltd
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Zhejiang University of Technology ZJUT
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Abstract

The invention discloses a method for preparing quinoxaline compounds shown in formula (I) and benzimidazole compounds shown in formula (II), which comprises the following steps: reacting allenic compounds shown in formula (III) in an inert organic solvent at 25-90 DEG C for 1-48 hours under the action of a catalyst, protonic acid and water; then adding oxalic acid and o-phenylenediamine, and reacting at 50-120 DEG C for 1-24 hours; and after the reaction, carrying out post treatment on the reaction liquid to obtain the quinoxaline compounds shown in formula (I) and the benzimidazole compounds shown in formula (II), wherein the catalyst is triphenyl gold chloride and silver tetrafluoroborate; the protonic acid is concentrated sulfuric acid, and methanesulfonic acid or p-toluenesulfonic acid or trifluoroacetic acid; and the inert organic solvent is an organic solvent which can not react with the allenic compounds. By using the one-pot method to prepare the quinoxaline compounds, the invention has the advantages of mild reaction conditions, convenient operation process and high product purity.

Description

A kind of quinoline the preparation method of cilin analog compound and benzimidazoles compound
(1) technical field
The present invention relates to a kind of preparation method of pharmaceutical intermediate, particularly a kind of quinoline the preparation method of cilin analog compound and benzimidazoles compound.
(2) background technology
Quinoline Nuo Xilin is a kind of important nitrogen-containing heterocycle compound, and many pharmacologically actives are arranged, as protozoacide, antibiotic, antimycotic and anticancer pharmacologically active.Synthetic quinoline the method in XiLin mainly be by 1, the condensation reaction of 2-diketone and O-Phenylene Diamine obtain (Alireza Hasaninejad, AbdolkarimZare, Mohammad Reza Mohammadizadeh, ARKIVOC (2008), xiii, 28-35).
Benzoglyoxaline is a kind of important nitrogen-containing heterocycle compound, and imidazole group plays the bioactive main effect of polypeptide and protein as the part of group amino side-chain.The imidazole group of functionalization also has many pharmacologically actives, as anti-HIV, anti-faint, calcium antagonist and inhibitor, antihistamine, effect (Synthetic Communications, 39 (18), 3232-3242 such as calm; 2009, E-Journal ofChemisrty, 5 (3), 447-452; 2008).Though the synthetic method of relevant quinoline Nuo Xilin and benzoglyoxaline has some reports, but still have a lot of defectives: as raw materials usedly be difficult to obtain, the scope of application is not wide, limitation is bigger, complex operation step, therefore the condition harshness has limited its applicability.
(3) summary of the invention
The object of the invention provide a kind of quinoline the preparation method of cilin analog compound and benzimidazoles compound, this method processing condition gentleness, use range is extensive, pass through one pot reaction, one-step synthesis quinoline cilin analog compound and benzimidazoles compound, the raw material that has overcome prior art is not easy to obtain, shortcomings such as complex operation.
The technical solution used in the present invention is:
Quinoline shown in a kind of formula (I) the preparation method of the benzimidazoles compound shown in cilin analog compound and the formula (II), described method is: the connection vinyl compound shown in the formula (III) is under the effect of catalyzer, protonic acid and water, in inert organic solvents, 25～90 ℃ of reaction 1～48h, add oxalic acid and O-Phenylene Diamine again in 50～120 ℃ of following reaction 1～24h, reaction finish with the reaction solution aftertreatment make the quinoline shown in the formula (I) the benzimidazoles compound shown in cilin analog compound and the formula (II); Described catalyzer is triphenyl gold trichloride and silver tetrafluoroborate; Described protonic acid is the vitriol oil, methylsulfonic acid, tosic acid or trifluoroacetic acid; Described inert organic solvents for not with the aitiogenic organic solvent of described vinyl compound, the feed intake ratio of amount of substance of connection vinyl compound shown in the described formula (III) and triphenyl gold trichloride, silver tetrafluoroborate is 1: 0.001～0.2: 0.001～0.2, connection vinyl compound shown in the described formula (III) is 1: 0.001～0.05: 0.05～40.0 with the ratio of the amount of substance that feeds intake of protonic acid, water, and the connection vinyl compound shown in the described formula (III) is 1: 0.01～0.4: 0.03～1.5 with the ratio of the amount of substance that feeds intake of oxalic acid, O-Phenylene Diamine;
Formula (I), (II) and (III) in R be phenyl, to butyl phenyl, to a bromophenyl or a fluorophenyl.
Described inert organic solvents is the halogenated hydrocarbon compound of C1～C4, the alkyl substituted benzene compounds of C7～C10, the aliphatic ether compounds of C2～C4 or the cyclic ether compounds of C4～C8, be preferably one of following: methylene dichloride, ethylene dichloride, toluene, ether, tetrahydrofuran (THF) or dioxane, more preferably dioxane.
Described protonic acid is preferably 95～98% vitriol oils.
Further, the feed intake ratio of amount of substance of connection vinyl compound shown in the described formula (III) and triphenyl gold trichloride, silver tetrafluoroborate is 1: 0.01～0.04: 0.04～0.16, connection vinyl compound shown in the described formula (III) is 1: 0.005～0.02: 8.3～33.4 with the ratio of the amount of substance that feeds intake of protonic acid, water, and the connection vinyl compound shown in the described formula (III) is 1: 0.2: 0.7 with the ratio of the amount of substance that feeds intake of oxalic acid, O-Phenylene Diamine.
The volumetric usage of described inert organic solvents is counted 0.5～5mL/mmol with the connection vinyl compound amount of substance shown in the formula (III).
Described quinoline the aftertreatment described in the preparation method of cilin analog compound and benzimidazoles compound be: after reaction finishes, add water in the reaction solution, use ethyl acetate extraction, get organic layer anhydrous sodium sulfate drying after-filtration, the chromatography column of packing into after the filtrate distillation removes and desolvates carries out column chromatography as follows:
(1) TLC followed the tracks of and collects R chromatography column as developping agent in 5: 1 with sherwood oil, ethyl acetate volume ratio earlier fValue is 0.6～0.7 elutriant, and elutriant removes eluent under reduced pressure, obtain the quinoline shown in the formula (I) cilin analog compound; Described TLC developping agent is 5: 1 sherwood oil of volume ratio, ethyl acetate mixture;
(2) TLC followed the tracks of and collects R chromatography column as developping agent in 3: 1 with sherwood oil, ethyl acetate volume ratio again fValue is 0.25～0.4 elutriant, and elutriant removes eluent under reduced pressure, obtains the benzimidazoles compound shown in the formula (II); Described TLC developping agent is 3: 1 sherwood oil of volume ratio, ethyl acetate mixture.
Further, preferred R in the described step (1) fBe worth the elutriant of collecting at 0.6～0.65 o'clock, remove eluent under reduced pressure, obtain the quinoline shown in the formula (I) cilin analog compound; In the described step (2), get R fValue is 0.3～0.35 o'clock elutriant of collecting, and removes eluent under reduced pressure, obtains the benzimidazoles compound shown in the formula (II).
Further, described quinoline cilin analog compound, the preparation method of benzimidazoles compound, described method recommends to carry out according to following steps: with connection vinyl compound and the triphenyl gold trichloride shown in the formula (III), silver tetrafluoroborate, the vitriol oil and water mix, in inert organic solvents, 50～80 ℃ of reaction 2～20h, add oxalic acid and O-Phenylene Diamine again and react 2～20h down in 60～90 ℃, TLC follows the tracks of reaction, reaction finishes reaction solution is added water, use ethyl acetate extraction, get organic layer anhydrous sodium sulfate drying after-filtration, the chromatography column of packing into after the filtrate distillation removes and desolvates carries out column chromatography, (1) chromatography column is earlier with sherwood oil, ethyl acetate volume ratio 5: 1 is carried out column chromatography as eluent, and TLC follows the tracks of and collects R fValue is 0.6～0.65 elutriant, and described step (1) TLC developping agent is 5: 1 sherwood oil of volume ratio, ethyl acetate mixture, and elutriant removes eluting solvent under reduced pressure, the quinoline shown in the acquisition formula (I) cilin analog compound; (2) chromatography column carries out column chromatography with sherwood oil, ethyl acetate volume ratio 3: 1 as eluent again, and TLC follows the tracks of and collects R fValue is 0.3～0.35 elutriant, and described step (2) TLC developping agent is 3: 1 sherwood oil of volume ratio, ethyl acetate mixture, and elutriant removes eluting solvent under reduced pressure, the benzimidazoles compound shown in the acquisition formula (II); Described inert organic solvents is methylene dichloride, ethylene dichloride, toluene, ether, tetrahydrofuran (THF) or dioxane; Connection vinyl compound shown in the described formula (III) and triphenyl gold trichloride, the feed intake ratio of amount of substance of silver tetrafluoroborate is 1: 0.01～0.04: 0.04～0.16, connection vinyl compound and protonic acid shown in the described formula (III), the ratio of the amount of substance that feeds intake of water is 1: 0.005～0.02: 8.3～33.4, connection vinyl compound and oxalic acid shown in the described formula (III), the ratio of the amount of substance that feeds intake of O-Phenylene Diamine is 1: 0.2: 0.7, and the volumetric usage of described inert organic solvents is counted 0.5～5mL/mmol with the connection vinyl compound amount of substance shown in the formula (III).
Compared with prior art, beneficial effect of the present invention is mainly reflected in: the present invention adopt one kettle way, a step preparation quinoline cilin analog compound and benzimidazoles compound, the reaction conditions gentleness, easy to operate, product purity is high, have the wide industrial application prospect arranged.
(4) embodiment
The present invention is described further below in conjunction with specific embodiment, but protection scope of the present invention is not limited in this:
Embodiment 1 quinoline cilin analog compound I-a, benzimidazoles compound II-a
With 58mg (0.5mmol) phenylpropyl alcohol diene, 4.94mg (0.01mmol) triphenylphosphine gold trichloride ((PPh) 3AuCl), 7.8mg (0.04mmol) silver tetrafluoroborate, 98% vitriol oil 2uL (0.005mmol) and 150uL (8.3mmol) water mix in the 1mL dioxane, 60 ℃ were reacted 24 hours down, add 37.8mg (0.35mmol) O-Phenylene Diamine again, 9.0mg (0.1mmol) oxalic acid, 80 ℃ of following back flow reaction 4 hours, TLC follows the tracks of detection, reaction finishes with ethyl acetate (50mL * 3) extraction, anhydrous sodium sulfate drying, filter, concentrate, (the chromatography column height is 20cm, and diameter is 1cm with the silica gel column chromatography separation; Elution flow rate is 1mL/min) (eluent: V Sherwood oil: V Ethyl acetate=5: 1), TLC (developping agent: V Sherwood oil: V Ethyl acetate=5: 1) follow the tracks of detection and collect R fValue 0.6～0.65 elutriant is removed eluent with the elutriant underpressure distillation, drying, obtain 2-methyl-3-phenyl quinazoline XiLin (I-a) 31.2mg, yield is 28.4%, orange solids; Then, column chromatography (eluent: V Sherwood oil: V Ethyl acetate=3: 1), TLC (developping agent: V Sherwood oil: V Ethyl acetate=3: 1) follow the tracks of detection and collect R fThe elutriant of value 0.3～0.35 is removed eluent with the elutriant underpressure distillation, and drying obtains 1-benzyl-2-Phenylbenzimidazole (II-a) 25.8mg, and yield is 36.4%, white solid.
1H?NMR(500MHz，CDCl 3)：
(I-a)：δ8.13-8.06(m，2H)，7.75-7.64(m，4H)，7.51-7.45-(m，3H)，2.78(s，3H)
(II-a)：δ7.88-7.86(m，1H)，7.70-7.68(m，2H)，7.48-7.43(m，3H)，7.35-7.20(m，6H)，7.11-7.10(m，2H)，5.46(s，2H).
Figure BDA0000057826120000051
Embodiment 2 quinolines cilin analog compound I-a, benzimidazoles compound II-a
Change dioxane into tetrahydrofuran (THF), other are operated with embodiment 1, obtain 2-methyl-3-phenyl quinazoline XiLin (I-a) 9.53mg, yield is 8.7%; 1-benzyl-2-Phenylbenzimidazole (II-a) 6.58mg, yield is 9.3%.
Embodiment 3
Change dioxane into toluene, other are operated with embodiment 1, obtain 2-methyl-3-phenyl quinazoline XiLin (I-a) 20.0mg, yield is 18.2%, 1-benzyl-2-Phenylbenzimidazole (II-a) 19.5mg, yield is 27.5%.
Embodiment 4
Change dioxane into 1, the 2-ethylene dichloride, other are operated with embodiment 1, obtain 2-methyl-3-phenyl quinazoline XiLin (I-a) 27.0mg, yield is 24.5%, 1-benzyl-2-Phenylbenzimidazole (II-a) 22.3mg, yield is 31.5%.
Embodiment 5
Change dioxane into ether, other are operated with embodiment 1, obtain 2-methyl-3-phenyl quinazoline XiLin (I-a) 13.9mg, yield is 12.6%, 1-benzyl-2-Phenylbenzimidazole (II-a) 15.5mg, yield is 21.8%.
Embodiment 6
Change 98% vitriol oil into trifluoroacetic acid, other are operated with embodiment 1, obtain 2-methyl-3-phenyl quinazoline XiLin (I-a) 26.1mg, yield is 23.7%, 1-benzyl-2-Phenylbenzimidazole (II-a) 21.6mg, yield is 30.4%.
Embodiment 7
Change 98% vitriol oil into methylsulfonic acid, other are operated with embodiment 1, obtain 2-methyl-3-phenyl quinazoline XiLin (I-a) 27.7mg, yield is 25.2%, 1-benzyl-2-Phenylbenzimidazole (II-a) 27.1mg, yield is 38.2%.
Embodiment 8
Change 98% vitriol oil into tosic acid, other are operated with embodiment 1, obtain 2-methyl-3-phenyl quinazoline XiLin (I-a) 18.6mg, yield is 16.9%, 1-benzyl-2-Phenylbenzimidazole (II-a) 19.7mg, yield is 27.8%.
Embodiment 9
Change the amount of 98% vitriol oil into 5.2uL (0.01mmol), other are operated with embodiment 1, obtain 2-methyl-3-phenyl quinazoline XiLin (I-a) 21.6mg, yield is 19.7%, 1-benzyl-2-Phenylbenzimidazole (II-a) 15.9mg, yield is 22.3%.
Embodiment 10
Change the amount of 98% vitriol oil into 0.65uL (0.0025mmol), other are operated with embodiment 1, obtain 2-methyl-3-phenyl quinazoline XiLin (I-a) 31.4mg, yield is 28.6%, 1-benzyl-2-Phenylbenzimidazole (II-a) 22.2mg, yield is 31.2%.
Embodiment 11
Change the amount of water into 0.075mL (4.17mmol), other are operated with embodiment 1, obtain 2-methyl-3-phenyl quinazoline XiLin (I-a) 13.0mg, yield is 9.4%, 1-benzyl-2-Phenylbenzimidazole (II-a) 20.3mg, yield is 20.5%
Embodiment 12
Change the amount of water into 0.3mL (16.7mmol), other are operated with embodiment 1, obtain 2-methyl-3-phenyl quinazoline XiLin (I-a) 26.2mg, yield is 19.0%, 1-benzyl-2-Phenylbenzimidazole (II-a) 17.2mg, yield is 17.4%
Embodiment 13
Change the amount of triphenylphosphine gold trichloride into 2.47mg (0.005mmol), other operations are with embodiment 1, obtain 2-methyl-3-phenyl quinazoline XiLin (I-a) 24.0mg, yield is 17.3%, 1-benzyl-2-Phenylbenzimidazole (II-a) 21.1mg, yield is 22.0%.
Embodiment 14
Change the amount of triphenylphosphine gold trichloride into 9.88mg (0.02mmol), other operations are with embodiment 1, obtain 2-methyl-3-phenyl quinazoline XiLin (I-a) 27.9mg, yield is 20.2%, 1-benzyl-2-Phenylbenzimidazole (II-a) 27.4mg, yield is 27.7%.
Embodiment 15
Change the amount of silver tetrafluoroborate into 3.9mg (0.02mmol), other are operated with embodiment 1, obtain 2-methyl-3-phenyl quinazoline XiLin (I-a) 20.9mg, yield is 15.1%, 1-benzyl-2-Phenylbenzimidazole (II-a) 18.4mg, yield is 18.4%.
Embodiment 16
Change the amount of silver tetrafluoroborate into 15.6mg (0.08mmol), other are operated with embodiment 1, obtain 2-methyl-3-phenyl quinazoline XiLin (I-a) 16.4mg, yield is 11.9%, 1-benzyl-2-Phenylbenzimidazole (II-a) 19.8mg, yield is 20.0%.
Embodiment 17 quinolines cilin analog compound (I-b), benzimidazoles compound (II-b)
With the butylbenzene propadiene is replaced the phenylpropyl alcohol diene, other are operated with embodiment 1, obtain target product formula (I-b) 45.0mg, and yield is 32.6%, orange solids, and target product formula (II-b) 33.8mg, yield is 34.2%, white solid.
1H?NMR(500MHz，CDCl 3)：
(I-b)：δ8.13-8.05(m，2H)，7.76-7.70(m，2H)，7.60-7.58(m，2H)，7.36-7.34(m，2H)，2.81(s，3H)，2.73-2.70(m，2H)，1.70-1.64(m，2H)，1.45-1.37(m，2H)，0.98-0.95(m，3H)；
(II-b)：δ7.86-7.84(m，1H)，7.62-7.61(m，2H)，7.30-7.20(m，5H)，7.13-7.12(m，2H)，7.02-7.00(m，2H)，5.42(s，2H)，2.67-2.57(m，4H)，1.63-1.56(m，4H)，1.38-1.24(m，4H)，0.94-0.91(m，6H).
Figure BDA0000057826120000081
Embodiment 18 quinolines cilin analog compound I-c
Replace the phenylpropyl alcohol diene with a fluorobenzene propadiene, other are operated with embodiment 1, obtain target product formula (I-c) 33.2mg, and yield is 27.9%, orange solids.
1H?NMR(500MHz，CDCl 3)：
(I-c)：δ8.13-8.06(m，2H)，7.79-7.73(m，2H)，7.54-7.38(m，3H)，7.23-7.19(m，1H)，2.80(s，3H).
Figure BDA0000057826120000082
Embodiment 19 quinolines cilin analog compound I-d, benzimidazoles compound II-d
With the bromobenzene propadiene is replaced the phenylpropyl alcohol diene, other are operated with embodiment 1, obtain target product formula (I-d) 48.9mg, and yield is 32.8%, orange solids, and target product formula (II-d) 31.6mg, yield is 28.7%, faint yellow solid.
1H?NMR(500MHz，CDCl 3)：
(I-d)：δ8.12-8.05(m，2H)，7.79-7.72(m，2H)，7.72-7.66(m，2H)，7.58-7.55(m，2H)，2.79(s，3H)；
(II-d)：δ7.88-7.87(m，1H)，7.70-7.68(m，2H)，7.50-7.43(m，3H)，7.35-7.21(m，4H)，7.10-7.11(m，2H)，5.46(s，1H).
Figure BDA0000057826120000092

Claims (10)

  1. Quinoline shown in the formula (I) the preparation method of the benzimidazoles compound shown in cilin analog compound and the formula (II), it is characterized in that described method is: the connection vinyl compound shown in the formula (III) is under the effect of catalyzer, protonic acid and water, in inert organic solvents, 25～90 ℃ of reaction 1～48h, add oxalic acid and O-Phenylene Diamine again in 50～120 ℃ of following reaction 1～24h, reaction finish with the reaction solution aftertreatment make the quinoline shown in the formula (I) the benzimidazoles compound shown in cilin analog compound and the formula (II); Described catalyzer is triphenyl gold trichloride and silver tetrafluoroborate; Described protonic acid is the vitriol oil, methylsulfonic acid, tosic acid or trifluoroacetic acid; Described inert organic solvents for not with the aitiogenic organic solvent of described vinyl compound, the feed intake ratio of amount of substance of connection vinyl compound shown in the described formula (III) and triphenyl gold trichloride, silver tetrafluoroborate is 1: 0.001～0.2: 0.001～0.2, connection vinyl compound shown in the described formula (III) is 1: 0.001～0.05: 0.05～40.0 with the ratio of the amount of substance that feeds intake of protonic acid, water, and the connection vinyl compound shown in the described formula (III) is 1: 0.01～0.4: 0.03～1.5 with the ratio of the amount of substance that feeds intake of oxalic acid, O-Phenylene Diamine;
    Figure FDA0000057826110000011
    Formula (I), (II) and (III) in R be phenyl, to butyl phenyl, to a bromophenyl or a fluorophenyl.
  2. Quinoline as claimed in claim 1 the preparation method of cilin analog compound, benzimidazoles compound, it is characterized in that described inert organic solvents is the halogenated hydrocarbon compound of C1～C4, the alkyl substituted benzene compounds of C7～C10, the aliphatic ether compounds of C2～C4 or the cyclic ether compounds of C4～C8.
  3. Quinoline as claimed in claim 1 or 2 the preparation method of cilin analog compound, benzimidazoles compound, it is characterized in that described inert organic solvents is one of following: methylene dichloride, ethylene dichloride, toluene, ether, tetrahydrofuran (THF) or dioxane.
  4. Quinoline as claimed in claim 1 or 2 the preparation method of cilin analog compound, benzimidazoles compound, it is characterized in that described inert organic solvents is a dioxane.
  5. Quinoline as claimed in claim 1 the preparation method of cilin analog compound, benzimidazoles compound, it is characterized in that described protonic acid is 95～98% vitriol oils.
  6. Quinoline as claimed in claim 1 the preparation method of cilin analog compound, benzimidazoles compound, it is characterized in that the feed intake ratio of amount of substance of the connection vinyl compound shown in the described formula (III) and triphenyl gold trichloride, silver tetrafluoroborate is 1: 0.01～0.04: 0.04～0.16, connection vinyl compound shown in the described formula (III) is 1: 0.005～0.02: 8.3～33.4 with the ratio of the amount of substance that feeds intake of protonic acid, water, and the connection vinyl compound shown in the described formula (III) is 1: 0.2: 0.7 with the ratio of the amount of substance that feeds intake of oxalic acid, O-Phenylene Diamine.
  7. Quinoline as claimed in claim 1 the preparation method of cilin analog compound, benzimidazoles compound, it is characterized in that the volumetric usage of described inert organic solvents is counted 0.5～5mL/mmol with the connection vinyl compound amount of substance shown in the formula (III).
  8. Quinoline as claimed in claim 1 the preparation method of cilin analog compound, benzimidazoles compound, it is characterized in that described aftertreatment is: after reaction finishes, add water in the reaction solution, use ethyl acetate extraction, get organic layer anhydrous sodium sulfate drying after-filtration, the chromatography column of packing into after the filtrate distillation removes and desolvates carries out column chromatography as follows:
    (1) chromatography column carries out column chromatography with sherwood oil, ethyl acetate volume ratio 5: 1 as eluent, and TLC follows the tracks of and collects R fValue is 0.6～0.7 elutriant, and elutriant removes eluent under reduced pressure, obtain the quinoline shown in the formula (I) cilin analog compound; The developping agent of described step (1) TLC is 5: 1 sherwood oil of volume ratio, ethyl acetate mixture;
    (2) TLC followed the tracks of and collects R chromatography column as eluent in 3: 1 with sherwood oil, ethyl acetate volume ratio again fValue is 0.25～0.4 elutriant, and elutriant removes eluent under reduced pressure, obtains the benzimidazoles compound shown in the formula (II); The developping agent of described step (2) TLC is 3: 1 sherwood oil of volume ratio, ethyl acetate mixture.
  9. Quinoline as claimed in claim 8 the preparation method of cilin analog compound, benzimidazoles compound, it is characterized in that getting R in the described step (1) fBe worth the elutriant of collecting at 0.6～0.65 o'clock, remove eluent under reduced pressure, obtain the quinoline shown in the formula (I) cilin analog compound; In the described step (2), get R fValue is 0.3～0.35 o'clock elutriant of collecting, and removes eluent under reduced pressure, obtains the benzimidazoles compound shown in the formula (II).
  10. Quinoline as claimed in claim 1 cilin analog compound, the preparation method of benzimidazoles compound, it is characterized in that described method carries out according to following steps: with connection vinyl compound and the triphenyl gold trichloride shown in the formula (III), silver tetrafluoroborate, the vitriol oil and water mix, in inert organic solvents, 50～80 ℃ of reaction 2～20h, add oxalic acid and O-Phenylene Diamine again and react 2～20h down in 60～90 ℃, TLC follows the tracks of reaction, reaction finishes reaction solution is added water, use ethyl acetate extraction, get organic layer anhydrous sodium sulfate drying after-filtration, the chromatography column of packing into after the filtrate distillation removes and desolvates carries out column chromatography, (1) chromatography column is earlier with sherwood oil, TLC followed the tracks of and collects R the ethyl acetate volume ratio as eluent in 5: 1 fValue is 0.6～0.65 elutriant, and elutriant removes eluent under reduced pressure, the quinoline shown in the acquisition formula (I) cilin analog compound; (2) TLC followed the tracks of and collects R chromatography column as eluent in 3: 1 with sherwood oil, ethyl acetate volume ratio again fValue is 0.3～0.35 elutriant, and elutriant removes eluent under reduced pressure, the benzimidazoles compound shown in the acquisition formula (II); Described inert organic solvents is methylene dichloride, ethylene dichloride, toluene, ether, tetrahydrofuran (THF) or dioxane; Connection vinyl compound shown in the described formula (III) and triphenyl gold trichloride, the feed intake ratio of amount of substance of silver tetrafluoroborate is 1: 0.01～0.04: 0.04～0.16, connection vinyl compound and protonic acid shown in the described formula (III), the ratio of the amount of substance that feeds intake of water is 1: 0.005～0.02: 8.3～33.4, connection vinyl compound and oxalic acid shown in the described formula (III), the ratio of the amount of substance that feeds intake of O-Phenylene Diamine is 1: 0.2: 0.7, and the volumetric usage of described inert organic solvents is counted 0.5～5mL/mmol with the connection vinyl compound amount of substance shown in the formula (III).
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