CN106279123B - 3- (benzenesulfonylmethyl) imidazoheterocycles class compound and its synthetic method - Google Patents
3- (benzenesulfonylmethyl) imidazoheterocycles class compound and its synthetic method Download PDFInfo
- Publication number
- CN106279123B CN106279123B CN201610666039.6A CN201610666039A CN106279123B CN 106279123 B CN106279123 B CN 106279123B CN 201610666039 A CN201610666039 A CN 201610666039A CN 106279123 B CN106279123 B CN 106279123B
- Authority
- CN
- China
- Prior art keywords
- imidazoheterocycles
- benzenesulfonylmethyl
- class compound
- class
- reaction
- 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.)
- Expired - Fee Related
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 37
- -1 benzenesulfonylmethyl Chemical group 0.000 title claims abstract description 18
- 238000010189 synthetic method Methods 0.000 title description 2
- 238000006243 chemical reaction Methods 0.000 claims abstract description 25
- 238000002360 preparation method Methods 0.000 claims abstract description 15
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims abstract description 10
- OHUDHPKMAJDBPI-UHFFFAOYSA-N isocyanomethylsulfonylbenzene Chemical class [C-]#[N+]CS(=O)(=O)C1=CC=CC=C1 OHUDHPKMAJDBPI-UHFFFAOYSA-N 0.000 claims abstract description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 238000007445 Chromatographic isolation Methods 0.000 claims abstract description 8
- 229940068918 polyethylene glycol 400 Drugs 0.000 claims abstract description 8
- 239000002904 solvent Substances 0.000 claims abstract description 7
- 238000000605 extraction Methods 0.000 claims abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 16
- 239000003480 eluent Substances 0.000 claims description 8
- 239000007789 gas Substances 0.000 claims description 8
- 239000003208 petroleum Substances 0.000 claims description 8
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 229940111121 antirheumatic drug quinolines Drugs 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical class C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 3
- 238000004587 chromatography analysis Methods 0.000 claims description 2
- 239000000284 extract Substances 0.000 claims description 2
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 claims 2
- FBAFATDZDUQKNH-UHFFFAOYSA-M iron chloride Chemical compound [Cl-].[Fe] FBAFATDZDUQKNH-UHFFFAOYSA-M 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 7
- VTLYFUHAOXGGBS-UHFFFAOYSA-N Fe3+ Chemical compound [Fe+3] VTLYFUHAOXGGBS-UHFFFAOYSA-N 0.000 abstract description 2
- 239000003054 catalyst Substances 0.000 abstract description 2
- 239000002184 metal Substances 0.000 abstract description 2
- 229910052751 metal Inorganic materials 0.000 abstract description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 abstract description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 24
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 14
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 7
- 229910052786 argon Inorganic materials 0.000 description 7
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 238000010828 elution Methods 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- VNHBYKHXBCYPBJ-UHFFFAOYSA-N 5-ethynylimidazo[1,2-a]pyridine Chemical class C#CC1=CC=CC2=NC=CN12 VNHBYKHXBCYPBJ-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- JRTIDHTUMYMPRU-UHFFFAOYSA-N alpidem Chemical compound N1=C2C=CC(Cl)=CN2C(CC(=O)N(CCC)CCC)=C1C1=CC=C(Cl)C=C1 JRTIDHTUMYMPRU-UHFFFAOYSA-N 0.000 description 2
- 229950008673 alpidem Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 2
- 150000003248 quinolines Chemical class 0.000 description 2
- LIFDPEORUVTOCP-UHFFFAOYSA-N saripidem Chemical compound N1=C2C=CC=CN2C(CN(C)C(=O)CCC)=C1C1=CC=C(Cl)C=C1 LIFDPEORUVTOCP-UHFFFAOYSA-N 0.000 description 2
- 229950007359 saripidem Drugs 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- ZAFYATHCZYHLPB-UHFFFAOYSA-N zolpidem Chemical compound N1=C2C=CC(C)=CN2C(CC(=O)N(C)C)=C1C1=CC=C(C)C=C1 ZAFYATHCZYHLPB-UHFFFAOYSA-N 0.000 description 2
- 229960001475 zolpidem Drugs 0.000 description 2
- UJZPJVGOWHZIKX-UHFFFAOYSA-N 2-(furan-2-yl)-1h-imidazole Chemical class C1=COC(C=2NC=CN=2)=C1 UJZPJVGOWHZIKX-UHFFFAOYSA-N 0.000 description 1
- 150000004941 2-phenylimidazoles Chemical class 0.000 description 1
- UZLSJAUHCCPJMC-UHFFFAOYSA-N 2-thiophen-2-yl-1h-imidazole Chemical class C1=CSC(C=2NC=CN=2)=C1 UZLSJAUHCCPJMC-UHFFFAOYSA-N 0.000 description 1
- KIKOMQUWWLUHTI-UHFFFAOYSA-N 2h-imidazo[2,1-b][1,3]thiazol-4-ium Chemical class C1=C[N+]2=CCSC2=N1 KIKOMQUWWLUHTI-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 0 CCCCCCl*[C@](CC)[C@@](C)[C@](C[C@](C)N=*)*C(C)=I Chemical compound CCCCCCl*[C@](CC)[C@@](C)[C@](C[C@](C)N=*)*C(C)=I 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000000767 anti-ulcer Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 230000000949 anxiolytic effect Effects 0.000 description 1
- 150000001538 azepines Chemical class 0.000 description 1
- 150000003851 azoles Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000006757 chemical reactions by type Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002240 furans Chemical class 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 239000005554 hypnotics and sedatives Substances 0.000 description 1
- RBQGKSWYSQGVDV-UHFFFAOYSA-N imidazo[2,1-b][1,3]benzothiazole Chemical compound C1=CC=C2N3C=CN=C3SC2=C1 RBQGKSWYSQGVDV-UHFFFAOYSA-N 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 150000002527 isonitriles Chemical class 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- YRMLUAGKHYADKJ-UHFFFAOYSA-N necopidem Chemical compound C1=CC(CC)=CC=C1C1=C(CN(C)C(=O)CC(C)C)N2C=C(C)C=CC2=N1 YRMLUAGKHYADKJ-UHFFFAOYSA-N 0.000 description 1
- 229950002306 necopidem Drugs 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 150000002916 oxazoles Chemical class 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 150000003233 pyrroles Chemical class 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 150000003557 thiazoles Chemical class 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of 3 (benzenesulfonylmethyl) imidazoheterocycles class compounds and preparation method thereof, include the following steps：Under ar gas environment, imidazoheterocycles class compound and benzenesulfonylmethyl isonitrile analog derivative are added in reaction tube, ferric trichloride is added, green solvent is then added, is reacted 18 ~ 48 hours at 80 ~ 120 DEG C；After reaction extraction, chromatographic isolation, be dried to obtain target product.The reaction is using cheap metal iron (III) as catalyst; water and polyethylene glycol 400 are as reaction dissolvent; imidazoheterocycles class compound is realized to react with the sulfonymethyl of benzenesulfonylmethyl isonitrile analog derivative; the sulfonyl of gained compound can be used as leaving group; realize that the research reacted the sulfonymethylization of imidazoheterocycles class compound and application are of great significance by further function dough reaction, this method.
Description
Technical field
The invention belongs to organic compound synthesis and applied technical fields, and in particular to a kind of 3- (benzenesulfonylmethyl) imidazoles
And the preparation method of heterocycle compound.
Background technology
Pyridine-imidazole is a kind of extremely important and common nitrogen heterocyclic（Comprehensive
Heterocyclic Chemistry III）.Its derivative has good bioactivity：For example, antiviral, antiulcer and anti-
Bacterium property（J. Med. Chem. 2015, 58, 8529; Bioorg. Med. Chem. Lett. 2013, 23, 4996;
J. Med. Chem. 2015, 58, 9238; Bioorg. Med. Chem. 2011, 19, 4227; ACS Med.
Chem. Lett. 2013, 4, 675; J. Med. Chem. 1999, 42, 50）.Wherein there are a few class drugs to succeed
Listing, such as anxiolytic drugs Alpidem（Alpidem), Saripidem（SariPidem）, arcotic Necopidem（How
It can pyrrole denier）With hypnotic sedative agent Zolpidem（Zolpidem）Deng（J. Med. Chem. 2008, 51, 7243; Exp.
Ther. 2001, 299, 793; J. Behav. Pharmacol. 1995, 6, 116）.Related pyridine-imidazole at present
The research for closing the function dough reaction of object and imidazoheterocycles class compound is gradually improved, but about the reaction of its sulfonymethylization
Research but has not been reported.
Toluenesulfomethyl isocyanide is widely used general in organic synthesis, utilizes its high activity and sulfonyl group
Easy leaving away property（Angew. Chem., Int. Ed. 2010, 49, 9094, Chem. Rev. 2010, 110, 5235,
Chem. Rev. 2015, 115, 2698）, synthesized the azepines such as a series of heterocyclic compound, such as pyrroles, oxazoles, imidazoles
Cycle compound（Chem. Commun. 2014, 50, 11837, Chem. Eur. J. 2015, 21, 18949, Org.
Lett. 2014, 16, 4004, Adv. Synth. Catal. 2014, 356, 2974）.This reaction is realized to toluene
Another reactive mode of sulfonymethyl isonitrile realizes sulfonymethylization using simple reaction system and reacts.
Invention content
The object of the present invention is to provide a kind of synthesis of 3- (benzenesulfonylmethyl) imidazoheterocycles class compound and preparation sides
Method, this method is simple and practicable, of low cost and be easy to purify.
To achieve the above object, the present invention uses following technical scheme：
A kind of 3- (benzenesulfonylmethyl) imidazoheterocycles class compound, general structure are：
Wherein X=C, O or S；N=0 or 1；R1For hydrogen, alkyl, alkoxy or halogen；Het is thiazoles, Thiazoling type, benzene
And thiazoles, quinolines Huo oxazole class heterocycles.
The preparation method of described 3- (benzenesulfonylmethyl) the imidazoheterocycles class compound, includes the following steps：In argon gas
Under environment, imidazoheterocycles class compound and benzenesulfonylmethyl isonitrile analog derivative are added in reaction tube, ferric trichloride is added,
Then green solvent is added, is reacted 18 ~ 48 hours at 80 ~ 120 DEG C；After reaction extraction, chromatographic isolation, be dried to obtain target
Product, reaction equation are as follows：
；
The general formula of the imidazoheterocycles class compound is：
The general structure of benzenesulfonylmethyl isonitrile analog derivative is：
Wherein X=C, O or S；n=0、1；R1For hydrogen, alkyl, alkoxy or halogen；Het is thiazoles, Thiazoling type, benzo
Thiazoles, quinolines Huo oxazole class heterocycles.
The amount ratio of the imidazoheterocycles class compound and the substance of benzenesulfonylmethyl isonitrile analog derivative is 1:2 or 1:3.
The dosage of the ferric trichloride is 0.1 ~ 0.3 times of the amount of the substance of imidazoheterocycles class compound.
The green solvent is water and polyethylene glycol 400 by volume 0 ~ 10:10 ~ 0 are mixed, with 0.1mmol miaows
On the basis of the amount of the substance of azoles and heterocycle compound, the dosage of the green solvent is 2mL.
The extractant used that extracts is dichloromethane.
The eluant, eluent that the chromatographic isolation uses is 0 ~ 100 for volume ratio：100 ~ 0 ethyl acetate and petroleum ether.
Beneficial effects of the present invention：The present invention provides a kind of easy-to-use side for synthesis imidazoheterocycles class compound
Method.The reaction using cheap metal iron (III) as catalyst, green non-poisonous water and polyethylene glycol 400 as reaction dissolvent,
Imidazoheterocycles class compound is realized to react with the sulfonymethyl of benzenesulfonylmethyl isonitrile analog derivative, gained compound
Sulfonyl can be used as leaving group, realize further function dough reaction, this will be provided more for the application of this method
Feasible way.This method is simple and efficient, of low cost and be easy to purify, and enriches the function of imidazoheterocycles class compound
Dough reaction type, while also realizing the new reactive mode of benzenesulfonylmethyl isonitrile analog derivative.This method will be to imidazo
The research and application of the sulfonymethylization reaction of heterocycle compound are of great significance.
Specific implementation mode
With reference to specific embodiment, the present invention will be further described.It should be understood that following embodiment is merely to illustrate this
The person skilled in the art of the range of invention and is not intended to limit the present invention, the field can make one according to the content of foregoing invention
A little nonessential modifications and adaptations.
Embodiment 1
Compound 2- (furans -2- bases) -3- (tosyl methyl) imidazo [1,2- of the present embodimenta] pyridine structure
For：
；
Preparation method：Under argon gas protection environment, the 2- furyl imidazoles of 0.1 mmol is added into 10 mL Shrek pipes
And [1,2-a] pyridine compounds, the toluenesulfomethyl isocyanide of 0.2 mmol, the ferric trichloride of 0.02mmol, 2 mL of water,
100 DEG C are reacted 36 hours；After reaction, it is extracted using dichloromethane, chromatographic isolation after reduced pressure（Silica gel 200-300
Mesh）, eluant, eluent：Ethyl acetate/petroleum ether gradient elution, ratio is by 0/100 to 100/0）, dry white solid, yield
90%。m.p. = 163-164℃. 1H NMR (600 MHz, CDCl3) δ 8.40 (d, J = 6.9 Hz, 1H), 7.60
(d, J = 9.1 Hz, 1H), 7.38 (d, J = 8.2 Hz, 2H), 7.32-7.29 (m, 1H), 7.13 (dd, J
= 1.6, 0.5 Hz, 1H), 7.06 (d, J = 7.9 Hz, 2H), 6.94 (td, J = 6.8, 1.0 Hz, 1H),
6.66 (d, J = 1.1 Hz, 1H), 6.31 (dd, J = 3.4, 1.8 Hz, 1H), 5.08 (s, 2H), 2.27
(s, 3H). 13C NMR (150 MHz, CDCl3) δ 149.1, 146.3, 145.1, 142.0, 137.8, 133.9,
129.2, 128.4, 126.3, 124.6, 117.3, 112.9, 111.1, 108.4, 108.0, 52.7, 21.5.
HRMS (positive ESI): [M+H]+ calcd for C19H17N2O3S+: 353.0954, found 353.0961.
Embodiment 2
Compound 2- (thiophene -2- bases) -3- (tosyl methyl) imidazo [1,2- of the present embodimenta] pyridine structure
For：
；
Preparation method：Under argon gas protection environment, the 2- thienyl imidazoles of 0.1 mmol is added into 10 mL Shrek pipes
And [1,2-a] pyridine compounds, the toluenesulfomethyl isocyanide of 0.3 mmol, the ferric trichloride of 0.03mmol, polyethylene glycol
400 2mL, 100 DEG C are reacted 18 hours；After reaction, it is extracted using dichloromethane, chromatographic isolation after reduced pressure（Silica gel
200-300 mesh）, eluant, eluent：Ethyl acetate/petroleum ether gradient elution, ratio is by 0/100 to 100/0）, dry white solid,
Yield 87%.m.p. = 161-162℃.1H NMR (600 MHz, CDCl3) δ 8.33 (d, J = 6.9 Hz, 1H),
7.64 (d, J = 9.1 Hz, 1H), 7.50 (d, J = 8.3 Hz, 2H), 7.31-7.26 (m, 2H), 7.15
(d, J = 8.0 Hz, 2H), 7.02 (dd, J = 3.6, 1.0 Hz, 1H), 6.95 (dd, J = 5.0, 3.7
Hz, 1H), 6.90 (td, J = 6.8, 1.0 Hz, 1H), 4.90 (s, 2H), 2.35 (s, 3H). 13C NMR
(150 MHz, CDCl3) δ 146.0, 145.5, 141.7, 135.9, 134.5, 129.9, 128.3, 127.4,
126.3, 126.1, 125.2, 124.6, 117.4, 113.0, 107.5, 53.1, 21.6. HRMS (positive
ESI): [M+H]+ calcd for C19H17N2O2S2 +: 369.0726, found 369.0730.
Embodiment 3
Compound 6- phenyl -5- (tosyl methyl) imidazo [2,1- of the present embodimentb] structural formula of thiazole is：
；
Preparation method：Under argon gas protection environment, the 6- phenylimidazoles of 0.1 mmol are added simultaneously into 10 mL Shrek pipes
[2,1-b] thiazolium compounds, the toluenesulfomethyl isocyanide of 0.3mmol, the ferric trichloride of 0.01mmol, water and polyethylene glycol
400 (volume ratios 7:3) 2 mL, 120 DEG C are reacted 24 hours；After reaction, it is extracted using dichloromethane, chromatography after reduced pressure
Separation（Silica gel 200-300 mesh）, eluant, eluent：Ethyl acetate/petroleum ether gradient elution, ratio is by 0/100 to 100/0）, dry
White solid, yield 85%. m.p. = 39-40℃.1H NMR (600 MHz, CDCl3) δ 7.71 (d, J = 4.5
Hz, 1H), 7.45 (d, J = 8.2 Hz, 2H), 7.24-7.23 (m, 3H), 7.18-7.14 (m, 4H), 6.90
(d, J = 4.5 Hz, 1H), 4.69 (s, 2H), 2.37 (s, 3H). 13C NMR (150 MHz, CDCl3) δ
150.9, 148.7, 145.4, 134.1, 133.2, 129.9, 128.29, 128.27, 127.8, 127.6,
119.1, 112.6, 109.8, 53.6, 21.6. HRMS (positive ESI): [M+H]+ calcd for
C19H17N2O2S2 +: 369.0726, found 369.0732.
Embodiment 4
Compound 6- phenyl -5- (tolysulfonyl ylmethyl) -2,3- glyoxalidine of the present embodiment simultaneously [2,1-b] thiazole
Structural formula be：
；
Preparation method：Under argon gas protection environment, 6- phenyl -2,3- of 0.1 mmol is added into 10 mL Shrek pipes
Glyoxalidine simultaneously [2,1-b] thiazolium compounds, the toluenesulfomethyl isocyanide of 0.3mmol, the ferric trichloride of 0.03mmol, water
With polyethylene glycol 400 (volume ratio 4:1) 2 mL, 80 DEG C are reacted 48 hours；After reaction, it is extracted, is depressurized using dichloromethane
Chromatographic isolation after concentration（Silica gel 200-300 mesh）, eluant, eluent：Ethyl acetate/petroleum ether gradient elution, ratio by 0/100 to
100/0）, dry white solid, yield 95%.m.p. = 48-49℃.1H NMR (600 MHz, CDCl3) δ 7.42
(d, J = 8.3 Hz, 2H), 7.18-7.15 (m, 3H), 7.10-7.08 (m, 4H), 4.48 (s, 2H), 4.38
(t, J = 7.3 Hz, 2H), 3.86 (t, J = 7.2 Hz, 2H), 2.34 (s, 3H). 13C NMR (150 MHz,
CDCl3) δ 151.3, 147.9, 145.3, 133.9, 133.3, 129.8, 128.2, 128.1, 127.2,
126.8, 114.0, 53.4, 46.3, 34.8, 21.6. HRMS (positive ESI): [M+H]+ calcd for
C19H19N2O2S2 +: 371.0882, found 371.0890.
Embodiment 5
The present embodiment compound 2- phenyl -3- (tolysulfonyl ylmethyl) benzo [d] imidazo [2,1-b] thiazole
Structural formula is：
；
Preparation method：Under argon gas protection environment, 2- phenyl-benzo of 0.1 mmol is added into 10 mL Shrek pipes
[d] imidazo [2,1-b] thiazolium compounds, the toluenesulfomethyl isocyanide of 0.3 mmol, the ferric trichloride of 0.03mmol, water
With polyethylene glycol 400 (volume ratio 3:2) 2 mL, 110 DEG C are reacted 24 hours；After reaction, it is extracted, is depressurized using dichloromethane
Chromatographic isolation after concentration（Silica gel 200-300 mesh）, eluant, eluent：Ethyl acetate/petroleum ether gradient elution, ratio by 0/100 to
100/0）, dry white solid, yield 41%. m.p. = 179-180℃.1H NMR (600 MHz, CDCl3) δ
8.08 (d, J = 8.3 Hz, 1H), 7.72 (d, J = 8.0 Hz, 1H), 7.52-7.49 (m, 1H), 7.39
(t, J = 7.8 Hz, 1H), 7.34 (d, J = 8.2 Hz, 2H), 7.24-7.22 (m, 5H), 5.08 (s,
2H), 2.33 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 149.7, 148.9, 145.2, 134.0,
133.1, 132.9, 130.2, 129.6, 128.3, 128.2, 127.7, 126.1, 125.0, 124.2, 114.7,
112.1, 52.8, 21.6. HRMS (positive ESI): [M+H]+ calcd for C23H19N2O2S2 +:
419.0882, found 419.0889.
Embodiment 6
Compound 2- phenyl -1- (tosyl methyl) imidazo [1,2- of the present embodimenta] structural formula of quinoline is：
；
Preparation method：Under argon gas protection environment, the 2- phenylimidazoles of 0.1 mmol are added simultaneously into 10 mL Shrek pipes
[1,2-a] quinoline compound, the toluenesulfomethyl isocyanide of 0.2 mmol, the ferric trichloride of 0.02mmol, water and poly- second two
(the volume ratio 3 of alcohol 400:2) 2 mL, 90 DEG C are reacted 24 hours；After reaction, it is extracted using dichloromethane, color after reduced pressure
Spectrum separation（Silica gel 200-300 mesh）, eluant, eluent：Ethyl acetate/petroleum ether gradient elution, ratio is by 0/100 to 100/0）, dry
Obtain white solid, yield 46%.m.p. = 184-185℃.1H NMR (600 MHz, CDCl3) δ 8.56 (d, J =
8.7 Hz, 1H), 7.83 (d, J = 7.7 Hz, 1H), 7.71 (t, J = 7.9 Hz, 1H), 7.59 (dd, J
= 14.5, 9.3 Hz, 2H), 7.52 (t, J = 7.5 Hz, 1H), 7,27 (s, 3H), 7.21-7.19 (m,
2H), 7.16 (d, J = 8.1 Hz, 2H), 6.95 (d, J = 8.0 Hz, 2H), 5.43 (s, 2H), 2.34
(s, 3H). 13C NMR (150 MHz, CDCl3) δ 148.4, 145.9, 144.9, 134.6, 134.5, 133.1,
129.54, 129.49, 128.7, 128.5, 128.4, 128.3, 128.1, 127.9, 125.1, 124.8,
117.2, 117.1, 112.3, 54.5, 21.6. HRMS (positive ESI): [M+H]+ calcd for
C25H21N2O2S+: 413.1318, found 413.1318.
The basic principles and main features and advantages of the present invention of the present invention have been shown and described above.The skill of the industry
Art personnel it should be appreciated that the present invention is not limited to the above embodiments, the above embodiments and description only describe
The principle of the present invention, without departing from the spirit and scope of the present invention, various changes and improvements may be made to the invention, these
Changes and improvements all fall within the protetion scope of the claimed invention.The claimed scope of the invention by appended claims and
Its equivalent thereof.
Claims (5)
1. a kind of preparation method of 3- (benzenesulfonylmethyl) imidazoheterocycles class compound, it is characterised in that include the following steps：
Under ar gas environment, imidazoheterocycles class compound and benzenesulfonylmethyl isonitrile analog derivative are added in reaction tube, are added three
Then green solvent is added in iron chloride, reacted 18 ~ 48 hours under conditions of 80 ~ 120 DEG C；Extraction, chromatography point after reaction
From, it is dry that target product, reaction equation are as follows：
；
The general structure of 3- (benzenesulfonylmethyl) the imidazoheterocycles class compound is：
Wherein X=C, O or S；N=0 or 1；R1For hydrogen, alkyl, alkoxy or halogen；Het is thiazoles, Thiazoling type, benzothiazole
Class, quinolines Huo oxazole class heterocycles；
The general formula of the imidazoheterocycles class compound is：
；
The general structure of the benzenesulfonylmethyl isonitrile analog derivative is：
；
Wherein X=C, O or S；N=0 or 1；R1For hydrogen, alkyl, alkoxy or halogen；Het is thiazoles, Thiazoling type, benzothiazole
Class, quinolines Huo oxazole class heterocycles；
The green solvent is water and polyethylene glycol 400 by volume 0 ~ 10:10 ~ 0 are mixed, with 0.1mmol imidazos
On the basis of the amount of the substance of heterocycle compound, the dosage of the green solvent is 2mL.
2. the preparation method of 3- (benzenesulfonylmethyl) imidazoheterocycles class compound according to claim 1, feature exist
In：The amount ratio of the imidazoheterocycles class compound and the substance of benzenesulfonylmethyl isonitrile analog derivative is 1:2 or 1:3.
3. the preparation method of 3- (benzenesulfonylmethyl) imidazoheterocycles class compound according to claim 1, feature exist
In：The dosage of the ferric trichloride is 0.1 ~ 0.3 times of the amount of the substance of imidazoheterocycles class compound.
4. the preparation method of 3- (benzenesulfonylmethyl) imidazoheterocycles class compound according to claim 1, feature exist
In：The extractant used that extracts is dichloromethane.
5. the preparation method of 3- (benzenesulfonylmethyl) imidazoheterocycles class compound according to claim 1, feature exist
In：The eluant, eluent that the chromatographic isolation uses is 0 ~ 100 for volume ratio：100 ~ 0 ethyl acetate and petroleum ether.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610666039.6A CN106279123B (en) | 2016-08-15 | 2016-08-15 | 3- (benzenesulfonylmethyl) imidazoheterocycles class compound and its synthetic method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610666039.6A CN106279123B (en) | 2016-08-15 | 2016-08-15 | 3- (benzenesulfonylmethyl) imidazoheterocycles class compound and its synthetic method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106279123A CN106279123A (en) | 2017-01-04 |
| CN106279123B true CN106279123B (en) | 2018-09-04 |
Family
ID=57670319
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610666039.6A Expired - Fee Related CN106279123B (en) | 2016-08-15 | 2016-08-15 | 3- (benzenesulfonylmethyl) imidazoheterocycles class compound and its synthetic method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106279123B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108997337A (en) * | 2018-08-10 | 2018-12-14 | 郑州大学 | N- (2- heterocyclic base imidazo heteroaromatic -3- base) dibenzenesulfonimide class compound and its synthetic method |
| CN109810105B (en) * | 2019-02-26 | 2020-07-17 | 郑州大学 | N- ((2-phenylimidazo [1,2-a ] pyridine-3-yl) methyl) aniline compound and synthetic method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0165545A2 (en) * | 1984-06-18 | 1985-12-27 | Fujisawa Pharmaceutical Co., Ltd. | Imidazoisoquinoline compounds and processes for preparation thereof |
| CN102869661A (en) * | 2010-03-18 | 2013-01-09 | 韩国巴斯德研究所 | Anti-infective compounds |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2009249186B2 (en) * | 2008-05-19 | 2014-05-22 | Sunovion Pharmaceuticals Inc. | Imidazo [1, 2-a] pyridine compounds as GABA-A receptor modulators |
| CA2953177C (en) * | 2014-06-23 | 2019-07-23 | Dr. Reddy's Laboratories Ltd. | Substituted imidazo[1,2-a]pyridine compounds useful for the treatment of pain |
-
2016
- 2016-08-15 CN CN201610666039.6A patent/CN106279123B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0165545A2 (en) * | 1984-06-18 | 1985-12-27 | Fujisawa Pharmaceutical Co., Ltd. | Imidazoisoquinoline compounds and processes for preparation thereof |
| CN102869661A (en) * | 2010-03-18 | 2013-01-09 | 韩国巴斯德研究所 | Anti-infective compounds |
Non-Patent Citations (1)
| Title |
|---|
| Microwave assisted novel and regioselective functionalization of imidazopyridines with chromene acetals and b-nitrostyrenes;L.Chandrasekhara Rao et al.;《RSC Advances》;20150812;第5卷;第70949-70957页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106279123A (en) | 2017-01-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Li et al. | Three-component synthesis of 2-heteroaryl-benzothiazoles under metal-free conditions | |
| Su et al. | Recent progress in the use of Vilsmeier-type reagents | |
| Cai et al. | Direct one-pot synthesis of zolimidine pharmaceutical drug and imidazo [1, 2-a] pyridine derivatives via I2/CuO-promoted tandem strategy | |
| Chandanshive et al. | 1, 3-Dipolar cycloaddition of nitrile imines with α, β-unsaturated lactones, thiolactones and lactams: synthesis of ring-fused pyrazoles | |
| CN106279159B (en) | 2 phenyl 3 (tosyl methyl) imidazo [1,2 a] pyridine compounds and theirs and its synthetic method | |
| CN106279123B (en) | 3- (benzenesulfonylmethyl) imidazoheterocycles class compound and its synthetic method | |
| Puttaraju et al. | Iodine-catalyzed three component reaction: a novel synthesis of 2-aryl-imidazo [1, 2-a] pyridine scaffolds | |
| CN107663209A (en) | 2 phenyl 3 (benzenesulfonyl) imidazo [1,2 a] pyridine compounds and theirs and its synthetic method | |
| Sheng et al. | Metal-free synthesis of imidazo [1, 5-a] pyridines via elemental sulfur mediated sequential dual oxidative Csp 3–H amination | |
| Low-Beinart et al. | Synthesis of pyrrolo-[2, 1-j] quinolone framework via intramolecular electrophilic ipso-cyclization | |
| CN102911105B (en) | 3-aroyl indole compound synthesis method | |
| Li et al. | One-step synthesis of furocoumarins via oxidative annulation of 4-hydroxycoumarins with DDQ | |
| Zhu et al. | One-pot three-component strategy for polysubstituted 2-aminothiazoles via ring opening of α-nitro epoxides | |
| CN108997337A (en) | N- (2- heterocyclic base imidazo heteroaromatic -3- base) dibenzenesulfonimide class compound and its synthetic method | |
| Wen et al. | DABCO-mediated isocyanide-based multicomponent reaction: synthesis of highly substituted cyclopentenes | |
| Guo et al. | CuI nanoparticle-catalyzed synthesis of tetracyclic benzo [e] benzo [4, 5] imidazo [1, 2-c][1, 3] thiazin-6-imine heterocycles by SN Ar-type C–S, C–N bond formation from isothiocyanatobenzenes and benzimidazoles | |
| Verma et al. | Construction of five-and six-membered heterocycles on both Cp rings of the ferrocene moiety of α-oxoketene-S, S-acetal and β-oxodithioester via heteroaromatic annulation | |
| Yan et al. | Copper acetate aerobic oxidative synthesis of pyrido [1, 2-a] benzimidazoles from aminopyridines and phenylboronic acids | |
| Shuvalov et al. | New Synthesis of Pyrazolo [3, 4-b] pyridine Derivatives Based on 5-Aminopyrazole and Azlactones | |
| Kumar et al. | Ru (ii)-Catalyzed, Cu (ii)-mediated carbene migratory insertion in the synthesis of trisubstituted pyrroles from isoxazoles | |
| CN105085520A (en) | 3-(2-nitro-1-phenylethyl)-2-(2-phenyl-imidazo[1,2-alpha] pyridine) compound | |
| CN106831765B (en) | 2- (2,6- dicyano phenyl) imidazo [1,2- α] pyridine compounds and their and preparation method thereof | |
| CN114716438B (en) | Benzo [7,8] indolizine [1,2-c ] quinoline skeleton derivative and synthetic method thereof | |
| Jiang et al. | Heterogeneous gold (I)-catalyzed cyclization between ynals and amidines: An efficient and practical synthesis of 2, 4-disubstituted pyrimidines | |
| Al-Trawneh et al. | A new efficient route to 7-aryl-6-fluoro-8-nitroquinolones as potent antibacterial agents |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20180904 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |