CN103588707A - Multi-nitrogen compound and synthesis method thereof - Google Patents

Multi-nitrogen compound and synthesis method thereof Download PDF

Info

Publication number
CN103588707A
CN103588707A CN201310229542.1A CN201310229542A CN103588707A CN 103588707 A CN103588707 A CN 103588707A CN 201310229542 A CN201310229542 A CN 201310229542A CN 103588707 A CN103588707 A CN 103588707A
Authority
CN
China
Prior art keywords
arh
amine
cdcl
nmr
benzyl
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.)
Granted
Application number
CN201310229542.1A
Other languages
Chinese (zh)
Other versions
CN103588707B (en
Inventor
麻生明
陈波
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shanghai Institute of Organic Chemistry of CAS
Original Assignee
Shanghai Institute of Organic Chemistry of CAS
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Shanghai Institute of Organic Chemistry of CAS filed Critical Shanghai Institute of Organic Chemistry of CAS
Priority to CN201310229542.1A priority Critical patent/CN103588707B/en
Publication of CN103588707A publication Critical patent/CN103588707A/en
Application granted granted Critical
Publication of CN103588707B publication Critical patent/CN103588707B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles

Abstract

The invention relates to a multi-nitrogen compound and a synthesis method thereof. The synthesis method is a synthesis method of a multi-nitrogen heterocyclic compound employing copper acetate to participate into multi-component reaction of 2,3- allenoic ester, amine and nitrile, namely an efficient synthesis method of pyrazole and a 1,2,4-triazole compound. By using the synthesis method, two multi-nitrogen heterocyclic compounds with important physiological activities, namely pyrazole and 1,2,4-triazole can be obtained from simple amine by adjusting whether the 2,3-allenoic ester is added or not. The compounds have the structural formulas as follows. By adopting the synthesis method, copper acetate is taken as an oxidant, and nitrile is taken as a solvent and a reactant, so that the two multi-nitrogen heterocyclic compounds with physiological activities are obtained from the 2,3-allenoic ester and the amine. The 1,2,4-triazole compound 4a synthetized by the method can be converted into a triazole salt compound with the antimalarial activity according to the known steps.

Description

Polyazin and synthetic method thereof
Technical field
The present invention relates to the synthetic of a kind of polyazin, refer to specifically the efficient synthetic of a kind of pyrazoles and 1,2,4-triazole compounds.Use this synthetic method, from simple amine, can whether add 2,3-connection olefin(e) acid ester to obtain two kinds of heterogeneous ring compounds with important physiologically active by regulating: pyrazoles and 1,2,4-triazole.
Background technology
In the various heterocycles with physiologically active, pyrazole heterocycle is one of most important skeleton, mainly due to it at wide application prospect (Fustero, S. aspect pharmaceutical industry and agrochemistry; S á nchez-Rosell ó, M.; Barrio, P.; Sim ó n-Fuentes, A.Chem.Rev.2011,111,6984-7034).Some contain pyrazoles framework compound, such as Rimonabant, and Celebrex, Viagra, and Fipronil has become commercial medicine and sterilant (structural formula 1) [(a) Terrett, N.K.; Bell, A.S.; Brown, D.; Ellis, P.Bioorg.Med.Chem.Lett.1996,6,1819 – 1824. (b) Christopoulou, F.D.; Kiortsis, D.N.J.Clin.Pharm.Ther.2011,36,10-18. (c) Gunasekara, A.S.; Truong, T.; Goh, K.S.; Spurlock, F.; Tjeerdema, R.S.J.Pestic.Sci.2007,32,189-199.].In addition, pyrazole compound is also applied to polymkeric substance, supramolecular chemistry, makeup and uses as UV stabilizer.The pyrazole compound replacing is used in some transition metal-catalyzed reactions as part.Therefore the method that, develops efficient, general synthesizing pyrazole skeleton has attracted the great interest of chemist.
Figure DEST_PATH_GDA0000438464400000021
Structural formula 1
As everyone knows, 1,2,4-triazole has very wide application (Moulin, A. in pharmaceutical chemistry; Bibian, M.; Blayo, A.-L.; El Habnouni, S.; Martinez, J.; Fehrentz, J.-A.Chem.Rev.2010,110,1809-1827.).Much contain 1,2,4-triazole class compounds is gone on the market to be sold for medicine, such as anastrozole, fluconazole, letrozole, mitratapide, voriconazole, maxalt, deferasirox, triadimefon, triadiminol, fluotrimazole, bitertanol, diclobutrazole, diniconazole, tebuconazole etc. (structural formula 2), all compounds (except Deferasirox) of coming of being listed are all containing having or not 1,2 of replacement below, 4-triazole female ring.Therefore, develop efficient, novel method and introduce different substituents to 1,2,4-triazole ring, for medicine chemical combination, man is significant.Up to now, directly by simple amine and nitrile, synthesize 1,2 of full replacement, 4-triazole have not been reported.
Structural formula 2
Multi-component reaction (MCR) is to prepare one of effective ways of complex compound by simple raw material, and it can one pot of efficient structure of realizing a plurality of chemical bonds, and does not need the intermediate of separation or purification reaction.This class reaction has simple to operate, and step is few, pollutes the advantages such as little, and multi-component reaction has become the focus of organic chemist's research.Along with the development gradually that connection alkylene is learned, the multi-component reaction that connection alkene participates in also becomes one of effective means building on various heterocycle skeletons.The present invention utilizes simple amine, and the multi-component reaction of 2,3-connection olefin(e) acid ester, nitrile, provides the efficiently approach of synthetic multi-substituted pyrazol compounds of a class.What is interesting is, without 2, under the condition of 3-connection olefin(e) acid ester, synthesized again 1,2,4-triazole class compounds.
The present invention utilizes neutralized verdigris as oxygenant, and nitrile is as solvent and reactant, from 2,3-connection olefin(e) acid ester and amine, obtains two kinds of heterogeneous ring compounds with physiologically active, for the synthetic of medicaments derivative of pyrazoles and triazole species, has a very big significance.
Summary of the invention
The object of this invention is to provide a kind of nitrogen catenation and synthetic method thereof.
Furtherly, one of object of the present invention is to provide multi-substituted pyrazol compounds.
Two of object of the present invention is to provide a kind of method of efficiently preparing multi-substituted pyrazol compounds.
It is a kind of 1,2 that three of object of the present invention is to provide, 4-triazole class compounds.
Four of object of the present invention is to provide a kind of efficient preparation 1,2, the method for 4-triazole class compounds.
A kind of nitrogen catenation provided by the invention: multi-substituted pyrazol (Pyrzole) and 1,2,4-triazole class compounds (1,2,3-trazole) there is following structural formula:
Figure BDA00003329383200031
Wherein, R 1=H or C 1～C 10alkyl, preferentially select C 1～C 4alkyl, R 2=benzyl, R 3=phenyl or C 1～C 10alkyl, R 4=C 1～C 12alkyl, benzyl, halogeno-benzyl, C 1～C 4alkyl benzyl or C 1～C 4alkoxybenzyl, R 5=phenyl, contain C 1～C 4alkyl phenyl.
The synthetic method of a kind of nitrogen catenation provided by the invention, reaction formula is as follows:
Figure BDA00003329383200041
Wherein, R 1, R 2, R 3, R 4, R 5as previously mentioned.
At 100-150 ℃ of temperature and in organic nitrile kind solvent, take neutralized verdigris as oxygenant, with amine and 2,3-, join olefin(e) acid ester for substrate, add or do not add molecular sieve water-removal agent, the reaction times is 6-48 hour,, generation pyrazole compound reacts; Wherein, described neutralized verdigris: the mol ratio of amine: 2,3-connection olefin(e) acid ester and molecular sieve is 1-3:1-2:0-1:0-5; Described mantoquita is preferably neutralized verdigris.What is interesting is, when described neutralized verdigris: when the mol ratio of amine: 2,3-connection olefin(e) acid ester and molecular sieve is 1-3:1-2:0.5-1:0-5, obtain pyrazole compound; When the mol ratio of described neutralized verdigris: amine: 2,3-connection olefin(e) acid ester and molecular sieve is 1-3:1-2:1:0:0-5, obtain 1,2,4-triazole class compounds.Described organic nitrile kind solvent can be C 1～C 10alkyl, phenyl or contain C 1～C 4alkyl phenyl, preferentially select cyanobenzene.Preferably 120 ℃ of temperature of reaction.
Further described method can be:
Pyrazole compound is synthetic
Under argon atmosphere, add successively 2,3-connection alkene acid benzyl ester in dry reaction tubes, amine and nitrile, after room temperature vigorous stirring 0.5h, add Cu (OAc) 2, being heated to 120 ℃, TLC monitors reaction, and after about 6-48 hour, raw material transforms completely, is back to room temperature, adds the dilution of 50mL ether, filter short column, filtrate is concentrated, and silica gel column chromatography obtains pyrazole compound.
Synthesizing of 1,2,4-triazole
In a dry reaction pipe, add successively Cu (OAc) 2, amine, nitrile, 120 degree reaction 20-48h, are cooled to room temperature, add the dilution of 50mL ether, filter short column, filtrate is concentrated, silica gel column chromatography obtains 1,2,4-triazole class compounds.
The inventive method has the following advantages: 1) reaction Raw is easy to preparation, and 2,3-connection olefin(e) acid ester can be prepared (Lang, R.W. in a large number; Hansen, H.-J.Org.Synth.1984,62,202.Rout, L.; Harned, A.M.Chem.Eur.J.2009,15,12926.), amine and nitrile are commercially available prod, and neutralized verdigris price is cheap; 2) efficiently polystep reaction one kettle way is realized; 3) fill up the blank of this type of framework compound synthetic method.
Embodiment
Following examples contribute to understand the present invention, but are not limited to content of the present invention.
Embodiment 1
Figure BDA00003329383200051
Wherein, equiv represents equivalent, and h represents hour.
Under argon atmosphere, add successively 2,3-connection alkene acid benzyl ester 1a (35.1mg, 0.2mmol) in dry Schlenk pipe, 2a (33.2mg, 0.3mmol) and cyanobenzene (1+1mL), after room temperature vigorous stirring 0.5h, add Cu (OAc) 2(72.9mg; 0.4mmol), system is put into oil bath, and oil bath is heated to 120 ℃; TLC monitors reaction; after approximately 6 hours, raw material transforms completely, is back to room temperature, adds the dilution of 50mL ether; filter short column; filtrate is concentrated, and silica gel column chromatography (sherwood oil petroleum ether/ ethyl acetate ethyl acetate=20/1) obtains 3a (57.9mg, 75%): oil; 1h NMR (300MHz, CDCl 3) δ 7.63-7.52 (m, 2H, ArH), 7.38-7.22 (m, 9H, ArH), 7.19-7.10 (m, 4H, ArH), 5.33 (s, 2H, OCH 2), 5.18 (s, 2H, NCH 2), 2.47 (s, 3H, CH 3); 13c NMR (75MHz, CDCl 3) δ 163.8,152.9,144.6,135.81,135.77,133.3,129.4,128.8,128.3,128.1,128.0,127.8,127.7,126.8,109.6,65.6,53.3,11.5; IR (pure sample neat) 1702,1539,1454,1293,1209,1158,1130,1066, cm -1; MS (EI) is 383 ((M+1) (m/z) +, 14.27), 382 (M +, 51.56), 91 (100); HRMS calculated value C 25h 22n 2o 2[M +]: 382.1681; Measured value (Found): 382.1679.
Embodiment 2
Figure BDA00003329383200061
Operation reference example 1.1a (35.1mg, 0.2mmol), 2b (37.5mg, 0.3mmol) Cu (OAc) 2(73.1mg, 0.4mmol) reacts and obtains 3b (64.8mg, 80%) (petroleum ether/ethyl acetate=10/1) in cyanobenzene (1+1mL), oil (oil); 1h NMR (400MHz, CDCl 3) δ 7.63-7.54 (m, 2H, ArH), 7.40-7.24 (m, 6H, ArH), 7.20-7.11 (m, 4H, ArH), 7.04-6.93 (m, 2H, ArH), 5.29 (s, 2H, OCH 2), 5.18 (s, 2H, NCH 2), 2.47 (s, 3H, CH 3); 13cNMR (75MHz, CDCl 3) δ 163.7,162.3 (d, J=245.0Hz), 152.9; 144.4,135.7,133.2,131.5 (d; J=3.4Hz), 129.3,128.6 (d, J=8.1Hz); 128.3,128.1,128.0,127.9; 127.7,115.7 (d, J=21.8Hz), 109.7; 65.6,52.5,11.4; 19f NMR (CDCl 3, 376MHz)-114.0; IR (neat) 2925,2853,1705,1606,1538,1510,1481,1450,1427,1375,1356,1318,1298,1215,1143,1111,1076cm -1; MS (EI) is 401 ((M+1) (m/z) +, 11.06), 400 (M +, 39.29), 109 (100); HRMS calculated value C 25h 21n 2o 2f[M +]: 400.1587; Measured value: 400.1589.
Embodiment 3
Operation reference example 1.1a (34.4mg, 0.2mmol), 2 (42.7mg, 0.3mmol), Cu (OAc) 2(72.7mg, 0.4mmol) reacts and obtains 3c (53.9mg, 65%) (petroleum ether/ethyl acetate=20/1to10/1) in cyanobenzene (1+1mL): oil; 1h NMR (300MHz, CDCl 3) δ 7.65-7.53 (m, 2H, ArH), 7.41-7.22 (m, 8H, ArH), 7.20-7.05 (m, 4H, ArH), 5.28 (s, 2H, OCH 2), 5.18 (s, 2H, NCH 2), 2.46 (s, 3H, CH 3); 13c NMR (75MHz, CDCl 3) δ 163.7,153.0,144.5,135.7,134.2,133.7,133.1,129.3,128.9,128.3,128.2,128.1,127.9,127.7,109.7,65.7,52.5,11.4; IR (neat) 2923,2851,1693,1489,1453,1291,1215,1162,1092,1065,1013cm -1; MS (EI) (m/z) 419 ((M ( 37cl)+1) +, 3.18), 418 (M ( 37cl) +, 11.66), 417 ((M ( 35cl)+1) +, 9.49), 416 (M ( 35cl) +, 32.75), 91 (100); HRMS calculated value C 25h 21n 2o 2 35cl[M +]: 416.1292; Measured value: 416.1289.
Embodiment 4
Figure BDA00003329383200071
Operation reference example 1.1a (33.8mg, 0.2mmol), 2d (41.5mg, 0.3mmol) Cu (OAc) 2(72.8mg, 0.4mmol) reacts and obtains 3d (48.7mg, 61%) (petroleum ether/ethyl acetate=10/1) in cyanobenzene (1+1mL): oil; 1h NMR (300MHz, CDCl 3) δ 7.65-7.53 (m, 2H, ArH), 7.37-7.29 (m, 3H, ArH), 7.29-7.20 (m, 3H, ArH), 7.20-7.08 (m, 4H, ArH), 6.89-6.78 (m, 2H, ArH), 5.26 (s, 2H, OCH 2), 5.17 (s, 2H, NCH 2), 3.75 (s, 3H, OMe), 2.47 (s, 3H, CH 3); 13c NMR (75MHz, CDCl 3) δ 163.8,159.2,152.7,144.3,135.8,133.4,129.4,128.28,128.26,128.0,127.9,127.8,127.6,114.1,109.6,65.6,55.2,52.8,11.4; IR (neat) 1701,1612,1586,1539,1513,1484,1453,1295,1248,1210,1129,1067,1030cm -1; MS (EI) is 413 ((M+1) (m/z) +, 3.77), 412 (M +, 13.05), 121 (100); HRMS calculated value C 26h 24n 2o 3[M +]: 412.1787; Measured value: 412.1789.
Embodiment 5
Operation reference example 1.1a (35.1mg, 0.2mmol), 2e (37.0mg, 0.3mmol) Cu (OAc) 2(72.5mg, 0.4mmol) reacts and obtains 3e (56.9mg, 71%) (petroleum ether/ethyl acetate=20/1) in cyanobenzene (1+1mL): solid; M.p.86-87 ℃ of (hexane/Et 2o); 1h NMR (300MHz, CDCl 3) δ 7.65-7.53 (m, 2H, ArH), 7.39-7.26 (m, 6H, ArH), 7.20-7.03 (m, 6H, ArH), 5.29 (s, 2H, OCH 2), 5.17 (s, 2H, NCH 2), 2.47 (s, 3H, CH 3), 2.30 (s, 3H, CH 3); 13c NMR (75MHz, CDCl 3) δ 163.8,152.8,144.4,137.6,135.8,133.3,132.7,129.40,129.35,128.3,128.0,127.9,127.8,127.7,126.8,109.5,65.6,53.1,21.0,11.5; IR (neat) 1695,1541,1515,1486,1451,1432,1291,1214,1158,1064cm -1; MS (EI) is 397 ((M+1) (m/z) +, 12.20), 396 (M +, 41.13), 105 (100); Ultimate analysis (elemental analysis) calculated value C 26h 24n 2o 2: C78.76, H6.10, N7.07; Measured value: C78.44, H6.16, N6.97.
Embodiment 6
Figure BDA00003329383200082
Operation reference example 1.1a (35.8mg, 0.2mmol), 2f (22.5mg, 0.3mmol) Cu (OAc) 2(72.7mg, 0.4mmol) reacts and obtains 3f (47.9mg, 67%) (petroleum ether/ethyl acetate=15/1to10/1) in cyanobenzene (1+1mL): oil; 1h NMR (400MHz, CDCl 3) δ 7.58-7.51 (m, 2H, ArH), 7.35-7.23 (m, 6H, ArH), 7.20-7.11 (m, 2H, ArH), 5.18 (s, 2H, OCH 2), 4.08 (t, J=7.4Hz, 2H, NCH 2), 2.55 (s, 3H, Me), 1.87-1.75 (m, 2H, CH 2), 1.41-1.30 (m, 2H, CH 2), 0.94 (t, J=7.4Hz, 3H, CH 3); 13c NMR (100MHz, CDCl 3) δ 163.9,152.6,143.8,135.9,133.5,129.3,128.2,128.0,127.84,127.78,127.6,108.8,65.5,49.0,31.9,19.8,13.6,11.3; IR (neat) 1951,1879,1807,1701,1538,1454,1296,1208,1161,1128,1068cm -1; MS (EI) is 349 ((M+1) (m/z) +, 13.05), 348 (M +, 53.02), 305 (100); HRMS calculated value C 22h 24n 2o 2[M +]: 348.1838; Measured value: 348.1840.
Embodiment 7
Figure BDA00003329383200091
Operation reference example 1.1a (36.6mg, 0.2mmol), 2g (31.7mg, 0.3mmol) Cu (OAc) 2(72.4mg, 0.4mmol) reacts and obtains 3g (44.4mg, 56%) (treat with20mg NaBH in cyanobenzene (1+1mL) 4, then petroleum ether/ethyl acetate=20/1): liquid; 1h NMR (300MHz, CDCl 3) δ 7.61-7.48 (m, 2H, ArH), 7.35-7.23 (m, 6H, ArH), 7.20-7.11 (m, 2H, ArH), 5.18 (s, 2H, OCH 2), 4.07 (t, J=7.4Hz, 2H, NCH 2), 2.55 (s, 3H, Me), 1.87-1.75 (m, 2H, CH 2), 1.40-1.23 (m, 6H, (CH 2) 3), 0.88 (t, J=6.9Hz, 3H, CH 3); 13c NMR (75MHz, CDCl 3) δ 163.9,152.6,143.8,135.9,133.6,129.3,128.3,128.0,127.84,127.78,127.6,108.8,65.5,49.3,31.3,29.9,26.2,22.4,13.9,11.3; IR (neat) 1950,1879,1806,1701,1537,1514,1485,1453,1297,1249,1159,1128,1067cm -1; MS (EI) is 377 ((M+1) (m/z) +, 8.67), 376 (M +, 32.26), 91 (100); HRMS calculated value C 24h 28n 2o 2[M +]: 376.2151; Measured value: 376.2150.
Embodiment 8
Figure BDA00003329383200101
Operation reference example 1.1a (35.4mg, 0.2mmol), 2h (39.0mg, 0.3mmol) Cu (OAc) 2(72.7mg, 0.4mmol) reacts and obtains 3h (49.3mg, 60%) (petroleum ether/ethyl acetate=20/1for twice) in cyanobenzene (1+1mL): liquid (liquid); 1h NMR (300MHz, CDCl 3) δ 7.59-7.48 (m, 2H, ArH), 7.37-7.23 (m, 6H, ArH), 7.20-7.09 (m, 2H, ArH), 5.18 (s, 2H, OCH 2), 4.08 (t, J=7.2Hz, 2H, NCH 2), 2.56 (s, 3H, Me), 1.92-1.75 (m, 2H, CH 2), 1.40-1.23 (m, 10H, (CH 2) 5), 0.87 (t, J=6.8Hz, 3H, CH 3); 13c NMR (75MHz, CDCl 3) δ 163.9,152.7,143.8,135.9,133.5,129.3,128.3,128.0,127.9,127.8,127.7,108.8,65.5,49.3,31.7,30.0,29.09,29.07,26.6,22.6,14.0,11.3; IR (neat) 1702,1537,1454,1297,1159,1128,1068cm -1; MS (EI) is 405 ((M+1) (m/z) +, 7.52), 404 (M +, 24.60), 91 (100); HRMS calculated value C 26h 32n 2o 2[M +]: 404.2464; Measured value: 404.2463.
Embodiment 9
Figure BDA00003329383200102
Operation reference example 1.1a (33.8mg, 0.2mmol), 2i (30.0mg, 0.3mmol) Cu (OAc) 2(72.9mg, 0.4mmol) reacts and obtains 3i (37.6mg, 52%) (twice of petroleum ether/ethyl acetate=20/1) in cyanobenzene (1+1mL): oil; 1h NMR (300MHz, CDCl 3) δ 7.58-7.48 (m, 2H, ArH), 7.36-7.22 (m, 6H, ArH), 7.16-7.09 (m, 2H, ArH), 5.17 (s, 2H, OCH 2), 4.05 (tt, J=11.6,3.8Hz, 1H, NCH), 2.57 (s, 3H, Me), 2.11-1.83 (m, 6H, (CH 2) 3), 1.75-1.64 (m, 1H, a proton (one proton in), CH 2), 1.50-1.20 (m, 3H, three protons (three proton in), (CH 2) 2); 13c NMR (75MHz, CDCl 3) δ 164.2,152.3,143.0,136.0,133.9,129.4,128.3,128.0,127.8,127.6,108.6,65.5,57.7,32.3,25.5,25.0,11.0; IR (neat) 2932,2856,1700,1537,1498,1451,1426,1299,1259,1221,1160,1151,1128,1091,1029cm -1; MS (EI) is 375 ((M+1) (m/z) +, 8.73), 374 (M +, 32.55), 185 (100); HRMS calculated value C 24h 26n 2o 2[M +]: 374.1994; Measured value: 374.1993.
Embodiment 10
Figure BDA00003329383200111
Wherein, equiv represents equivalent, and h represents hour, and MS represents molecular sieve.
Operation reference example 1.1a (34.9mg, 0.2mmol), 2a (32.3mg, 0.3mmol),
Figure BDA00003329383200112
mS (50.0mg), Cu (OAc) 2(72.9mg, 0.4mmol) exists nbuCN (1+1mL) reaction obtains 3j (35.4mg, 49%) (petroleum ether/ethyl acetate=10/1): oil; 1h NMR (300MHz, CDCl 3) δ 7.50-7.22 (m, 8H, ArH), 7.15-7.04 (m, 2H, ArH), 5.27 (s, 2H, OCH 2), 5.25 (s, 2H, NCH 2), 2.90-2.78 (m, 2H, CH 2), 2.42 (s, 3H, Me), 1.68-1.52 (m, 2H, CH 2), 1.40-1.22 (m, 2H, CH 2), 0.87 (t, J=7.2Hz, 3H, CH 3); 13c NMR (75MHz, CDCl 3) δ 164.2,154.9,144.4,136.2,136.1,128.7,128.5,128.3,128.1,127.7,126.6,109.1,65.6,52.9,31.7,28.2,22.7,13.9,11.4; IR (neat) 2956,2930,1702,1546,1496,1455,1305,1235,1211,1189,1113,1086,1029cm -1; MS (EI) is 362 (M (m/z) +, 2.90), 91 (100); HRMS calculated value C 23h 26n 2o 2[M +]: 362.1994; Measured value: 362.1996.
Embodiment 11
Figure BDA00003329383200121
Wherein, equiv represents equivalent, and h represents hour, and sealed represents tube sealing
Operation reference example 1.1a (34.7mg, 0.2mmol), 2a (32.4mg, 0.3mmol) Cu (OAc) 2(72.8mg, 0.4mmol) reacts and obtains 3k (38.3mg, 60%) (petroleum ether/ethyl acetate=10/1to5/1) in MeCN (1+1mL): oil; 1h NMR (400MHz, CDCl 3) δ 7.45-7.24 (m, 8H, ArH), 7.13-7.04 (m, 2H, ArH), 5.28 (s, 2H, OCH 2), 5.24 (s, 2H, NCH 2), 2.45 (s, 3H, CH 3), 2.43 (s, 3H, CH 3); 13c NMR (100MHz, CDCl 3) δ 164.2,150.7,144.4,136.3,136.0,128.8,128.5,128.03,127.98,127.8,126.6,109.7,65.5,52.8,14.5,11.4; IR (neat) 1685,1549,1495,1452,1430,1372,1295,1271,1205,1194,1115cm -1; MS (EI) is 320 (M (m/z) +, 15.65), 91 (100); HRMS calculated value C 20h 20n 2o 2[M +]: 320.1525; Measured value: 320.1526.
Embodiment 12
Figure BDA00003329383200122
Wherein, equiv represents equivalent, and h represents hour, and oil bath represents oil bath heating.
In a dry Schlenk reaction tubes, add successively Cu (OAc) 2(367.9mg, 2mmol), n-Butyl Amine 99 BnNH 2(108.6mg; 1mmol); PhCN (2mL), after adding puts into system 120 ℃ of oil baths that heat in advance, reaction 20h; be cooled to room temperature; add the dilution of 50mL ether, filter short column, filtrate is concentrated; silica gel column chromatography (eluent:petroleum ether/ethyl acetate=40/1to10/1) to afford4a (139.7mg, 44%): solid; 1h NMR (300MHz, CDCl 3) δ 8.25-8.14 (m, 2H, ArH), 7.66-7.57 (m, 2H, ArH), 7.52-7.27 (m, 9H, ArH), 7.25-7.16 (m, 2H, ArH), 5.46 (s, 2 H, CH 2).
The synthetic 4a of gram level:
In a dry 100mL there-necked flask, add successively Cu (OAc) 2(3.6321g, 20mmol), BnNH 2(1.0704g; 10mmol); PhCN (20mL). after adding, system is put into 120 ℃ of oil baths that heat in advance; reaction 48h, is cooled to room temperature, adds the dilution of 50mL ether; filter short column; filtrate is concentrated, and silica gel column chromatography (eluent:petroleum ether/ethyl acetate=30/1to10/1) obtains 4a (1.3062g, 42%): solid; 1h NMR (300MHz, CDCl 3) δ 8.27-8.14 (m, 2H, ArH), 7.64-7.52 (m, 2H, ArH), 7.48-7.13 (m, 11H, ArH), 5.40 (s, 2H, CH 2).
Figure BDA00003329383200131
Wherein, equiv represents equivalent, and mins represents minute, and MW represents microwave heating.
In a dry microwave reaction pipe, add successively Cu (OAc) 2(363.9mg, 2mmol), BnNH 2(106.8mg, 1mmol), PhCN (5mL), tightens cock, puts into microwave reactor MILESTONE S.r.l
Figure BDA00003329383200132
(120 ℃ of microwave heatings; 30minutes; maximum power800W); then treat that system is cooled to room temperature; add the dilution of 50mL ether, filter short column, filtrate is removed most of solvent at oil pump decompression backspin; silica gel column chromatography (eluent:petroleum ether/ethyl acetate=10/1) obtains 4a (127.0mg, 41%): solid (solid); M.p.99-100 ℃ of (hexane hexane/ ether Et 2o) (lit.m.p.98.5-99.5 ℃); 1h NMR (300MHz, CDCl 3) δ 8.21 (d, J=7.2Hz, 2H, ArH), 7.62-7.51 (m, 2H, ArH), 7.48-7.13 (m, 11H, ArH), 5.39 (s, 2H, CH 2); 13c NMR (CDCl 3, 75MHz) δ 161.4,156.0, and 135.9,130.9,130.0,129.0,128.70,128.67,128.6,128.4,127.9,127.8,126.6,126.3,52.6.IR (neat) 3067,3035,2926,2854,1519,1497,1476,1463,1443,1406,1353,1266,1237,1131,1072,1016cm -1; MS (EI) is 312 ((M+1) (m/z) +, 5.71), 311 (M +, 27.09), 91 (100).
This compound is known compound, can pass through known steps one step (Vlahakis, J.Z.; Lazar, C.; Crandall, I.E.; Szarek, W.A.Biorg.Med.Chem.2010,18,6184) be converted into the triazolium salt compound with antiplasmodial activities
Figure BDA00003329383200141
iC 50(7.8 ± 0.2 μ M) P.falciparum.
Embodiment 13
Figure BDA00003329383200142
Operation reference example 13.Cu (OAc) 2(362.4mg, 2mmol), 4-fluorobenzene methylamine 4-fluorobenzylamine (129.7mg; 97%purity; 1mmol), in PhCN (5mL), reaction obtains 4b (150.3mg, 45%) (eluent:petroleum ether/ethyl acetate=10/1): oil; 1h NMR (300MHz, CDCl 3) δ 8.24-8.16 (m, 2H, ArH), 7.64-7.52 (m, 2H, ArH), 7.50-7.33 (m, 6H, ArH), 7.20-7.10 (m, 2H, ArH), 7.05-6.92 (m, 2H, ArH), 5.37 (s, 2H, NCH 2); 13c NMR (CDCl 3, 75MHz) δ 162.2 (d, J=245.9Hz), 161.5,155.9,131.6 (d, J=3.5Hz); 130.8,130.2,129.2,128.8,128.63,128.61 (d, J=8.1Hz); 128.45,127.8,126.3,115.7 (d, J=20.9Hz), 51.9; 19f NMR (CDCl 3, 282MHz)-113.9; IR (neat) 1605,1509,1478,1458,1446,1405,1353,1222,1156,1141,1016cm -1; MS (EI) is 330 ((M+1) (m/z) +, 11.24), 329 (M +, 49.41), 109 (100); HRMS calculated value C 21h 16n 3f(M +): 329.1328, measured value: 329.1329.
Embodiment 14
Figure BDA00003329383200151
Operation reference example 13.Cu (OAc) 2(363.9mg, 2mmol), n-butylamine n-BuNH 2(73.1mg, 1mmol), in PhCN (5mL), reaction obtains 4c (147.8mg, 53%) (leacheate eluent:petroleum ether/ethyl acetate=10/1): oil; 1h NMR (300MHz, CDCl 3) δ 8.19 (d, J=7.2Hz, 2H, ArH), 7.66-7.61 (m, 2H, ArH), 7.60-7.24 (m, 6H, ArH), 4.18 (t, J=7.2Hz, 2H, NCH 2), 2.00-1.83 (m, 2H, CH 2), 1.40-1.21 (m, 2H, CH 2), 0.86 (t, J=7.2Hz, 3H, CH 3); 13c NMR (CDCl 3, 75MHz) δ 161.0,155.3, and 131.1,129.8,128.8,128.6,128.3,126.2,48.8,31.9,19.5,13.3; IR (neat) 3068,2959,2933,2873,1957,1893,1815,1767,1519,1476,1463,1442,1410,1354,1132,1019cm -1; MS (EI) is 278 ((M+1) (m/z) +, 11.49), 277 (M +, 55.63), 234 (100); HRMS calculated value C 18h 19n 3(M +): 277.1579, measured value: 277.1578.
Figure BDA00003329383200152
Cu (OAc) 2(363.2mg, 2mmol), n-BuNH 2(74.0mg, 1mmol), obtains 4c (125.3mg, 45%) (eluent:petroleum ether/ethyl acetate=10/1) in PhCN (2mL) reaction: oil; 1h NMR (300MHz, CDCl 3) δ 8.18 (d, J=7.5Hz, 2H, ArH), 7.66-7.60 (m, 2H, ArH), 7.59-7.30 (m, 6H, ArH), 4.20 (t, J=7.2Hz, 2H, NCH 2), 2.00-1.80 (m, 2H, CH 2), 1.40-1.21 (m, 2H, CH 2), 0.87 (t, J=7.2Hz, 3H, CH 3).
Embodiment 15
Figure BDA00003329383200153
Operation reference example 13.Cu (OAc) 2(362.5mg, 2mmol), isobutylamine isobutylNH 2(74.1mg, 1mmol), in PhCN (5mL), reaction obtains 4d (132.4mg, 47%) (eluent:petroleum ether/ethyl acetate=10/1): oil; 1h NMR (300MHz, CDCl 3) δ 8.19 (d, J=7.2Hz, 2H, ArH), 7.68-7.57 (m, 2H, ArH), 7.55-7.30 (m, 6H, ArH), 4.02 (d, J=7.2Hz, 2H, NCH 2), 2.45-2.25 (m, 1H, CH), 0.86 (d, J=6.6Hz, 6H, (CH 3) 2); 13c NMR (CDCl 3, 75MHz) δ 161.0,156.0, and 131.1,129.8,128.9,128.7,128.5,128.4,126.3,56.2,29.2,19.7; IR (neat) 3069,2940,2872,1958,1894,1815,1730,1519,1476,1463,1442,1409,1391,1354,1285,1193,1174,1132,1071,1018cm -1; MS (EI) is 278 ((M+1) (m/z) +, 14.65), 277 (M +, 67.21), 104 (100); HRMS calculated value C 18h 19n 3(M +): 277.1579, measured value: 277.1577.
Embodiment 16
Figure BDA00003329383200161
Operation reference example 13.Cu (OAc) 2(363.3mg, 2mmol), n-pentyl amine n-C 5h 11nH 2(88.1mg, 1mmol), in PhCN (5mL), reaction obtains 4e (135.1mg, 46%) (eluent:petroleum ether/ethyl acetate=15/1): oil; 1h NMR (300MHz, CDCl 3) δ 8.18 (d, J=7.5Hz, 2H, ArH), 7.72-7.60 (m, 2H, ArH), 7.55-7.30 (m, 6H, ArH), 4.19 (t, J=7.4Hz, 2H, NCH 2), 2.00-1.82 (m, 2H, CH 2), 1.38-1.20 (m, 4H ,-(CH 2) 2-), 0.85 (t, J=5.9Hz, 3H, CH3); 13c NMR (CDCl 3, 75MHz) δ 161.1,155.4, and 131.1,129.9,128.9,128.7,128.4,126.3,49.2,29.7,28.5,22.0,13.8; IR (neat) 2958,2926,2856,1476,1463,1441,1408,1355cm -1; MS (EI) is 292 ((M+1) (m/z) +, 12.96), 291 (M +, 59.60), 234 (100); HRMS calculated value C 19h 21n 3(M +): 291.1735, measured value: 291.1734.
Embodiment 17
Figure BDA00003329383200171
Operation reference example 13.Cu (OAc) 2(363.1mg, 2mmol), cyclo-hexylamine CyNH 2(99.4mg, 1mmol), in PhCN (5mL), reaction obtains 19f (137.7mg, 45%) (eluent:petroleum ether/ethyl acetate=10/1): solid, 107-108 ℃ of (petroleum ether/Et 2o) (lit. 2m.p.106-107 ℃); 1h NMR (300MHz, CDCl 3) δ 8.18 (d, J=7.8Hz, 2H, ArH), 7.68-7.57 (m, 2H, ArH), 7.56-7.47 (m, 3H, ArH), 7.46-7.30 (m, 3H, ArH), 4.22 (tt, J=11.4,4.1Hz, 1H, NCH 2), 2.23-2.02 (m, 2H, CH 2), 2.02-1.80 (m, 4H ,-(CH 2) 2-), 1.78-1.61 (m, 1H, one proton in CH 2), 1.40-1.20 (m, 3H, three proton in (CH 2) 2); 13c NMR (CDCl 3, 75MHz) δ 160.9,154.6, and 131.4,129.8,128.9,128.8,128.7,128.4,126.3,58.0,33.1,25.4,24.9; IR (neat) 3060,3032,2928,2853,1476,1439,1402,1380,1350,1326,1300,1263,1174,1026cm -1; MS (EI) is 304 ((M+1) (m/z) +, 8.77), 303 (M +, 36.94), 221 (100).
Embodiment 18
Figure BDA00003329383200172
Operation reference example 13.Cu (OAc) 2(363.5mg, 2mmol), n-hexyl amine n-hexylNH 2(102.0mg, 1mmol), in PhCN (5mL), reaction obtains 4g (146.1mg, 48%) (eluent:petroleum ether/ethyl acetate=10/1): oil; 1h NMR (400MHz, CDCl 3) δ 8.17 (d, J=7.2Hz, 2H, ArH), 7.70-7.63 (m, 2H, ArH), 7.59-7.50 (m, 3H, ArH), 7.49-7.35 (m, 3H, ArH), 4.21 (t, J=7.4Hz, 2H, NCH 2), 2.00-1.87 (m, 2H, CH 2), 1.36-1.20 (m, 6 H ,-(CH2) 3-), 0.85 (t, J=6.8Hz, 3H, CH 3); 13c NMR (CDCl 3, 75MHz) δ 161.1,155.4, and 131.2,129.9,128.9,128.8,128.4,126.3,49.2,31.1,30.0,26.1,22.4,13.9; IR (neat) 3069,2954,2929,2857,1956,1893,1814,1764,1519,1476,1442,1410,1353,1132,1071,1018cm -1; MS (EI) is 306 ((M+1) (m/z) +, 11.44), 305 (M +, 50.21), 234 (100); HRMS calculated value C 20h 23n 3(M +): 305.1892, measured value: 305.1893.
Embodiment 19
Operation reference example 13.Cu (OAc) 2(363.8mg, 2mmol), n-octylamine n-C 8h 17nH 2(128.5mg, 1mmol), in PhCN (5mL), reaction obtains 4h (166.9mg, 50%) (eluent:petroleum ether/ethyl acetate=15/1): oil; 1h NMR (300MHz, CDCl 3) δ 8.18 (d, J=7.8Hz, 2H, ArH), 7.67-7.60 (m, 2H, ArH), 7.53-7.30 (m, 6H, ArH), 4.19 (t, J=7.4Hz, 2H, NCH 2), 2.00-1.83 (m, 2H, CH 2), 1.38-1.07 (m, 10H ,-(CH 2) 5-), 0.85 (t, J=6.5Hz, 3H, CH 3); 13c NMR (CDCl 3, 75MHz) δ 161.0,155.4, and 131.1,129.8,128.9,128.7,128.4,126.2,49.1,31.6,30.0,28.9,28.8,26.3,22.5,13.9; IR (neat) 2926,2855,1955,1893,1813,1727,1519,1476,1442,1354,1133,1071cm -1; MS (EI) is 334 ((M+1) (m/z) +, 3.84), 333 (M +, 17.96), 221 (100).
Operation reference example 13.Cu (OAc) 2(363.4mg, 2mmol), n-C 8h 17nH 2(128.9mg, 1mmol), in PhCN (2mL), oil bath reaction obtains 4h (143.6mg, 43%) (eluent:petroleum ether/ethyl acetate=10/1): oil; 1h NMR (300MHz, CDCl 3) δ 8.22 (m, 2H, ArH), 7.69-7.60 (m, 2H, ArH), 7.55-7.30 (m, 6H, ArH), 4.20 (t, J=7.4Hz, 2H, NCH 2), 2.00-1.84 (m, 2H, CH 2), 1.38-1.10 (m, 10H ,-(CH 2) 5-), 0.86 (t, J=6.8Hz, 3H, CH 3).
Embodiment 20
Figure BDA00003329383200191
Operation reference example 13.Cu (OAc) 2(363.4mg, 2mmol), dodecyl amine n-C 12h 25nH 2(185.7mg, 1mmol), in PhCN (5mL), reaction obtains 4i (214.7mg, 55%) (eluent:petroleum ether/ethyl acetate=10/1): oil; 1h NMR (300MHz, CDCl 3) δ 8.17 (d, J=7.5Hz, 2H, ArH), 7.72-7.60 (m, 2H, ArH), 7.58-7.30 (m, 6H, ArH), 4.20 (t, J=7.2Hz, 2H, NCH 2), 2.00-1.82 (m, 2H, CH 2), 1.38-1.12 (m, 18H ,-(CH 2) 9-), 0.88 (t, J=6.0Hz, 3H, CH 3); 13c NMR (CDCl 3, 75MHz) δ 161.1,155.5, and 131.2,129.9,128.9,128.81,128.79,128.4,126.3,49.2,31.8,30.1,29.5,29.4,29.34,29.27,28.9,26.4,22.6,14.1; IR (neat) 2924,2853,1953,1891,1812,1763,1464,1442,1354,1018cm -1; MS (EI) is 390 ((M+1) (m/z) +, 5.76), 389 (M +, 19.41), 221 (100); HRMS calculated value C 26h 35n 3(M +): 389.2831, measured value: 389.2832.
Embodiment 21
Figure BDA00003329383200192
Operation reference example 13.Cu (OAc) 2(363.4mg, 2mmol), benzylamine BnNH 2(107.1mg, 1 mmol), in PhCN (2mL), reaction obtains 4j (163.8mg, 48%) (eluent:petroleum ether/ethyl acetate=15/1): oil; 1h NMR (300MHz, CDCl 3) δ 8.10-7.95 (m, 2H, ArH), 7.46 (s, 1H, ArH), 7.39-7.15 (m, 10H, ArH), 5.40 (s, 2H, NCH 2), 2.38 (s, 3H, Me), 2.33 (s, 3H, Me); 13c NMR (CDCl 3, 75MHz) δ 161.4,156.0, and 138.5,138.0,136.0,130.7,130.0,129.8,129.4,128.6,128.5,128.3,127.71,127.67,126.8,126.6,125.4,123.4,52.5,21.19,21.14; IR (neat) 1611,1592,1512,1496,1452,1433,1358,1339,1301,1262,1143cm -1; MS (EI) is 340 ((M+1) (m/z) +, 23.42), 339 (M +, 94.69), 91 (100); HRMS calculated value C 23h 21n 3(M +): 339.1735, measured value: 339.1736.

Claims (6)

1. a polyazin, it has multi-substituted pyrazol or 1,2, the 4-triazole class compounds of following structural formula:
Figure FDA00003329383100011
Wherein, R 1=H or C 1～C 10alkyl, R 2=benzyl, R 3=phenyl or C 1～C 10alkyl, R 4=C 1～C 12alkyl, benzyl, halogeno-benzyl, C 1～C 4alkyl substituted benzyl base or C 1～C 4alkoxyl group substituted benzyl, R 5=phenyl, contain C 1～C 4alkyl-substituted phenyl.
2. a synthetic method for polyazin as claimed in claim 1, is characterized in that obtaining by following step:
Figure FDA00003329383100012
At 100-150 ℃ of temperature and in organic nitrile kind solvent, take neutralized verdigris as oxygenant, with amine and 2,3-, join olefin(e) acid ester for substrate, add or do not add molecular sieve water-removal agent, the reaction times is 6-48 hour, generation pyrazole compound reacts; Wherein, described neutralized verdigris: the mol ratio of amine: 2,3-connection olefin(e) acid ester and molecular sieve is 1-3:1-2:0-1:0-5;
Described, R 1, R 2, R, R 4and R 5definition with described in claim 1.
3. the synthetic method of polyazin as claimed in claim 2, is characterized in that, when the mol ratio of described neutralized verdigris: amine: 2,3-connection olefin(e) acid ester and molecular sieve is 1-3:1-2:0.5-1:0-5, obtains pyrazole compound.
4. the synthetic method of polyazin as claimed in claim 2, is characterized in that, when the mol ratio of described neutralized verdigris: amine: 2,3-connection olefin(e) acid ester and molecular sieve is 1-3:1-2:1:0:0-5, obtains 1,2,4-triazole class compounds.
5. the synthetic method of polyazin as claimed in claim 2 or claim 3, is characterized in that, described 1,2, R in 4-triazole class compounds 5=phenyl, R 4=n-octylamine, phenyl or benzyl.
6. the synthetic method of multi-substituted pyrazol as claimed in claim 2 and 1,2,4-triazole class compounds, is characterized in that: described product is through ether dilution, and short column is separated, and filtrate is concentrated, purification by silica gel column chromatography.
CN201310229542.1A 2013-06-09 2013-06-09 Polyazin and synthetic method thereof Active CN103588707B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201310229542.1A CN103588707B (en) 2013-06-09 2013-06-09 Polyazin and synthetic method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201310229542.1A CN103588707B (en) 2013-06-09 2013-06-09 Polyazin and synthetic method thereof

Publications (2)

Publication Number Publication Date
CN103588707A true CN103588707A (en) 2014-02-19
CN103588707B CN103588707B (en) 2016-06-01

Family

ID=50079060

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201310229542.1A Active CN103588707B (en) 2013-06-09 2013-06-09 Polyazin and synthetic method thereof

Country Status (1)

Country Link
CN (1) CN103588707B (en)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020032184A1 (en) * 2000-07-07 2002-03-14 Corbau Romuald Gaston Pyrazole derivatives
KR20100015080A (en) * 2008-08-04 2010-02-12 이화여자대학교 산학협력단 Process of preparing pyrazoles
WO2011120861A1 (en) * 2010-03-29 2011-10-06 Westfälishe Wilhelms-Universität Münster Pyrazole synthesis by coupling of carboxylic acid derivatives and enamines

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020032184A1 (en) * 2000-07-07 2002-03-14 Corbau Romuald Gaston Pyrazole derivatives
KR20100015080A (en) * 2008-08-04 2010-02-12 이화여자대학교 산학협력단 Process of preparing pyrazoles
WO2011120861A1 (en) * 2010-03-29 2011-10-06 Westfälishe Wilhelms-Universität Münster Pyrazole synthesis by coupling of carboxylic acid derivatives and enamines

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
JULIA J. NEUMANN等: "Efficient Synthesis of Pyrazoles：Oxidative C－C/N－N Bond-Formation Cascade", 《ANGEW. CHEM. INT. ED.》, vol. 49, 6 September 2010 (2010-09-06), pages 7790 - 7794 *
ODD REIDAR GAUTUN等: "Substituent effects in the rearrangement of 4-alkyl-4H-1,2,4-trizoles", 《ACTA CHEMICA SCANDINAVICA》, vol. 48, 31 December 1994 (1994-12-31), pages 411 - 416 *
PER H.J. CARLSEN等: "Thermolysis of N-Allylic-1,2,4-Triazoles", 《J.HETEROCYCLIC CHEM.》, vol. 34, 30 June 1997 (1997-06-30), pages 797 - 806 *

Also Published As

Publication number Publication date
CN103588707B (en) 2016-06-01

Similar Documents

Publication Publication Date Title
CN113336689B (en) Synthesis method and anticancer activity of 3- (alpha-fluorovinyl/carbonyl) indole compound
CN109232363B (en) Synthetic method of 3-selenocyanoindole compound
CN110452270B (en) Azacarbene palladium complex crystal, synthesis method thereof and application thereof in preparation of alpha, beta-unsaturated ketone compound
Cao et al. Direct Enamido C (sp2)− H Diphosphorylation Enabled by a PCET‐Triggered Double Radical Relay: Access to gem‐Bisphosphonates
CN110437124A (en) A kind of indoles quinone derivative and preparation method thereof
CN104072429B (en) A kind of synthetic method of 1,2,4-triazole derivative
CN106699632A (en) Preparation method of 3-methylene isoindole-1-one derivatives
CN103588707B (en) Polyazin and synthetic method thereof
CN111454194A (en) Method for preparing phenyl-2-indolyl selenium sulfone compound for treating cerebral ischemia through magnesium catalysis
CN104610267B (en) Method for efficiently synthesizing 6-alkyl pyrazolo [1,5-c ] quinazoline framework compound under non-catalytic condition
CN114835652B (en) Method for synthesizing iminobenzotriazole compound under photocatalysis condition
CN109851544A (en) A kind of preparation method of polysubstituted pyrrole compound
CN110156673B (en) Method for preparing quinoline compound by catalysis of zirconocene dichloride
Ma et al. Alkali salt-catalyzed aza-Michael addition of 1, 2, 4-triazole to α, β-unsaturated ketones and imides
CN110028448B (en) Preparation method of 3-hydroxy-2,3-dihydroisoquinoline-1, 4-diketone compound
CN112442025B (en) Method for synthesizing imidazo [1, 2a ] pyridine compound
CN107382899B (en) Polysubstituted 2-hydroxy-1, 4-benzoxazine derivative
CN113603679B (en) Synthesis method and anticancer activity of 2-hydroxysuccinimide substituted indolone compound
CN110590636A (en) 4-sulfonyl pyrrolidone compound and synthesis method thereof
CN110845423A (en) Preparation method of 1, 2-substituted benzimidazole compound
CN110526850A (en) The preparation method of 2,5- diaryl -3- cyanopyrrole compound
CN111004164A (en) Preparation method of polysubstituted 2-aryl indole derivative
CN114751868B (en) Diaryl substituted triazole acetic acid compound, and preparation method and application thereof
CN114214646B (en) Synthesis method of electrochemical oxidation 2-trifluoromethyl-alpha-carbonyl dithio ketene compound
CN112194604B (en) Beta-sulfuryl hydrazone derivative and preparation method and application thereof

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant