CN106366069A - Preparation method of N-heteroaryl carbazole compounds - Google Patents

Preparation method of N-heteroaryl carbazole compounds Download PDF

Info

Publication number
CN106366069A
CN106366069A CN201610769719.0A CN201610769719A CN106366069A CN 106366069 A CN106366069 A CN 106366069A CN 201610769719 A CN201610769719 A CN 201610769719A CN 106366069 A CN106366069 A CN 106366069A
Authority
CN
China
Prior art keywords
carbazole
derivant
formula
heteroaryl
bromo
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
CN201610769719.0A
Other languages
Chinese (zh)
Other versions
CN106366069B (en
Inventor
佘远斌
李贵杰
赵向东
方坤
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.)
Zhejiang University of Technology ZJUT
Original Assignee
Zhejiang University of Technology ZJUT
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 Zhejiang University of Technology ZJUT filed Critical Zhejiang University of Technology ZJUT
Priority to CN201610769719.0A priority Critical patent/CN106366069B/en
Publication of CN106366069A publication Critical patent/CN106366069A/en
Application granted granted Critical
Publication of CN106366069B publication Critical patent/CN106366069B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen 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
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Indole Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

The invention relates to a preparation method of N-heteroaryl carbazole compounds. The method comprises the following steps: by using carbazole compounds and heteroaryl halides as raw materials, Cu (I) salt as a catalyst and 1-methylimidazole as a ligand, carrying out reaction in an organic solvent at 110-130 DEG C in a nitrogen protective atmosphere in the presence of an alkaline matter tert-butyl alcohol lithium for 1.2 hours-5.0 days; and after the reaction finishes, carrying out separation purification on the reaction mixture to obtain the N-heteroaryl carbazole compounds disclosed as Formula (I), Formula (II) or Formula (III), wherein the heteroaryl halides are heteroaryl bromides or heteroaryl iodides. The method has the advantages of low raw material price, simple reaction technique and operation and high yield (up to 90% or above), is suitable for mass preparation and industrialization, and has wide application prospects.

Description

A kind of preparation method of n- heteroaryl carbazole compound
Technical field
The present invention relates to a kind of preparation method of n- heteroaryl carbazole compound.
Background technology
N- heteroaryl carbazole compound is the important organic functional material of a class, in field of organic electroluminescent materials (oled) have a wide range of applications.Such compound, due to having good heat stability, electrochemical stability and electric conductivity, is The important component part of Phosphorescent luminescent material, acts not only as the auxiliary group of phosphorescent molecules, in specific molecule knot The four ring gear metal platinum developing in recent years and the luminous material of palladium complex phosphorescence can also be widely present in as luminophore in structure (angew.chem.int.ed.2013,52,6753 in material；org.electronics,2014,15,1862； adv.mater.2014,26,7116；acs appl.mater.&interfaces,2015,7,16240；adv.optical mater.2015,3,390；adv.mater.2015,27,2533).Secondly, n- heteroaryl carbazole structure unit exists in In oled device main body material 9- { 2- [6- (9- carbazyl)-pyridine radicals] } carbazole (26-mcpy) molecular structure, because it is good Performance, this material of main part is widely used (adv.mater.2007,19,197) in oled device.Additionally, n- is miscellaneous Heteroaryl in aryl carbazole class compound also by as a kind of homing device, induces transition metal palladium and the carbazole α of ruthenium catalysis The functionalization of position hydrogen, the such as (organometallics 2013,32,272 such as the arylation of α position hydrogen, acetoxylation； Org.lett.2016,18,1150), therefore also have a wide range of applications in terms of organic synthesiss.
The arylation reaction of nitrogen heteroatom not only has a wide range of applications in organic functional material field, Er Qieju J.med.chem.2016,59,4385 reports, in 30 years of past, this kind of reaction is also that two the most frequently used classes of drugmaker have Machine synthesis one of method for transformation, its most representational reaction be Massachusetts Institute Technology buchwald professor and now take office in The coupling reaction of the c-n key of relevant palladium chtalyst of professor's hartwig development of University of California Berkeley, referred to as Buchwald-hartwig reacts (nature protocols 2007,2,2881；angew.chem.int.ed.2008,47, 6338；acc.chem.res.2008,41,1534；chem.sci.2011,2,27).But such reaction needs to use noble metal As catalyst, the Phosphine ligands of xenyl phosphine part used and big steric hindrance are also costly and synthesize more numerous for palladium class compound Trivial；Additionally due to heavy metal palladium toxicity is larger, medicine production also exists heavy-metal residual problem.Buchwald teaches Award the arylation reaction that organic with Shanghai horse such as greatly teaches at the nitrogen heteroatom that have also been developed mantoquita catalysis, enter in this regard Go extensively in-depth study achieve good result.It is catalyst that such reaction typically adopts Hydro-Giene (Water Science). (cui), And a lot of catalysts consumption is generally large, it is 10% even more many；Experimental studies have found that part reaction is had critically important Effect, for different types of substrate, need to select appropriate part that reaction can be made to be smoothed out to obtain good receipts Rate；Part used is generally phenodiazine, nitrogen oxygen and dioxy class part, such as trans-cyclohexanediamine, trans-n, n- dimethyleyelohexane two Amine, 1,10- phenanthroline and its derivant, amino acidses, adjacent dicarbapentaborane class compound etc., some of which catalytic performance is good Part expensive or need laboratory to synthesize, the application that is unfavorable for preparing in a large number (nature protocols 2007,2, 2474；chem.sci.2010,1,13；j.am.chem.soc.2015,137,11942).And current, not yet there is carbazoles chemical combination The systematic study report that thing is coupled with 2- bromopyridine class compound.2011, the yum of Korea S taught in document The carbazole of microwave assisted and the coupling of 2- bromopyridine under 10%cui catalysis are reported on tetrahedron2011,67,4820 anti- Should, but up to 220 DEG C of reaction temperature, and need with more expensive cs2co3Do alkali, microwave reaction is unfavorable for a large amount of of product in addition Preparation；The same year bull.korean.chem.soc.2011,32,2461 reports this reaction also can be under licl promotes at 150 DEG C Carry out, but reaction yield only has 74%, and unclear to the facilitation principle of licl.In research before, we send out Now with k2co3For alkaline matter, n- Methylimidazole. is catalyst, and 10%cui can be catalyzed the coupling of 2- bromine carbazole and 2- bromopyridine, Reaction needs to carry out in tube sealing, in order that 2- bromine carbazole reaction completely, will add the 2- bromopyridine of 3 equivalents, and reaction is carried out Very slow, generally require 3-6 days；In addition excessive 2- bromopyridine and product are difficult to separate, and this greatly reduces the effect of organic synthesiss Rate (adv.optical mater.2015,3,396；us 2014/0364605 a1).Adv.mater.2014,26,7116 and Us 9224963 b2 reports pd2(dba)3The carbazole derivates of/johnphos catalysis and the idol of 2- bromo- 4- tert .-butylpyridine Connection, yield reaches more than 80%, but catalyst and part are expensive, and equally expensive 2- bromo- 4- tert .-butylpyridine needs greatly Excessive greatly.Professor kobyashi of Japan in 2016 achieves carbazole and the 2- iodine pyridine that visible ray promotes lower 10%cui catalysis Coupling reaction, yield is up to 93%, but is intended to use precious metal chemical complex ir (ppy)3Make photocatalyst.
In sum although being related to prepare the report of the synthetic method in n- heteroaryl carbazole compound, but still And do not have the system synthesis research report to such compound, and generally existing uses noble metal catalyst, response time length, receipts Rate is low, be difficult to the shortcomings of prepare in a large number, therefore how to design a kind of cheap, succinct, the efficiently such compound of synthesis method Just seem very necessary.
Content of the invention
It is an object of the invention to provide a kind of preparation method of n- heteroaryl carbazole compound.The method can be honest and clean Valency, succinct, be efficiently synthesized n- (2- pyridine radicals) carbazoles and n- (2- thiazolyl) carbazole compound, it is possible to achieve suchization The even more substantial preparation of tens grams of levels of compound.
The technical solution used in the present invention is as follows:
A kind of preparation method of n- heteroaryl carbazole compound, methods described specifically sequentially includes the following steps:
With carbazole compound and hetaryl halogenides as raw material, cu (i) salt is catalyst, and 1- Methylimidazole. is part, React in organic solvent at 110～130 DEG C 1.2 hours in nitrogen protective condition in the presence of alkaline matter tert-butyl alcohol lithium ～5 days, reaction is followed the tracks of by tlc, after question response terminates, reactant mixture is isolated and purified, obtain formula (i), formula (ii) or formula (iii) the n- heteroaryl carbazole compound shown in；For the compound shown in formula (i) or formula (iii), described carbazoles Compound is 1:1.1～3 with the ratio of the amount of the material of hetaryl halogenides；For the compound shown in formula (ii), described carbazole Class compound is 2.2～4:1 with the ratio of the amount of the material of hetaryl halogenides；Described hetaryl halogenides are hetaryl bromides Or heteroaryl iodide,
In formula (i): x, y each stand alone as n or ch；In formula (iii): z is o, s or nr；
R in formula (i), formula (ii) and formula (iii)1～r10Identical, r1～r19Each stand alone as h or, h is by deuterium, halogen, alkane Base or adjacent two substituent groups form benzo ring substituents with the heteroaryl being connected and replace.
Further, when in preferably described formula (i), x, y are ch, r2For bromine, remaining substituent group each stand alone as h or, h Replaced with the heteroaryl being connected by deuterium, halogen, alkyl or adjacent two substituent groups；Or r3For bromine, remaining substituent group is each Stand alone as h or, h is replaced with the heteroaryl being connected by deuterium, halogen, alkyl or adjacent two substituent groups.
Further, in preferably described formula (i), x is n, when y is ch, r1～r10Each stand alone as h or, h by deuterium, halogen, Alkyl or adjacent two substituent groups are replaced with the heteroaryl being connected.
Further, in preferably described formula (i), x is ch, when y is n, r1～r10Each stand alone as h or, h by deuterium, halogen, Alkyl or adjacent two substituent groups are replaced with the heteroaryl being connected.
Further, r in preferably described formula (ii)1～r19It is alkyl substituent.
Further, when in preferably described formula (iii), z is s, r1～r10Each stand alone as h or, h is by deuterium, halogen, alkyl Or two adjacent substituent groups are replaced with the heteroaryl being connected.
Further, when in preferably described formula (iii), z is nme, r1～r10Each stand alone as h or, h by deuterium, halogen, Alkyl or adjacent two substituent groups are monosubstituted with the heteroaryl being connected or polysubstituted.
Further, described carbazole compound is carbazole, 2- bromine carbazole, 3- bromine carbazole, 2,7- dibromo carbazole, 3,6- bis- Bromine carbazole, 3- phenyl carbazole, 3,6- di-t-butyl bromine carbazole or 1,3,6- tri-tert bromine carbazole.
Further, described hetaryl halogenides are 2- bromopyridine and its derivant, 2,6- dibromo pyridines and its derivant, 2- bromoquinoline and its derivant, 2- bromo-isoquinoline and its derivant, 2- bromo-pyrazine and its derivant, 2,5- bis- bromo-pyrazines and its spread out Biology, 2- Bromopyrimidine and its derivant, the bromo- 1,3,5-triazines of 2- and its derivant, bromo- 1,2, the 5- triazines of 2- and its derivant, 2- bromo thiazole and its derivant, 2- bromo benzothiazole and its derivant, 2- bromobenzene imidazole and its derivants, 2- iodine pyridine and its Derivant, 2,6- diiodopyridines and its derivant, 2- iodine quinoline and its derivant, 2- iodine isoquinolin and its derivant, 2- iodine pyrrole Piperazine and its derivant, 2,5- diiodo- pyrazines and its derivant, 2- iodine pyrimidine and its derivant, the iodo- 1,3,5-triazines of 2- and its spread out Biology, iodo- 1,2, the 5- triazines of 2- and its derivant, 2- iodine thiazole and its derivant, 2- iodine benzothiazole and its derivant, 2- iodine Benzimidazole and its derivant and their bromoiodide.
Further, described catalyst cu (i) salt is Hydro-Giene (Water Science)., Cu-lyt. or cuprous bromide.
Further, described catalyst cu (i) salt and the ratio of the amount of carbazole compound material are 0.01～0.1:1, more Further, preferably 0.01～0.05:1.
Further, described ligand 1-Methylimidazole. and the ratio of the amount of cu (i) salt catalyst material enter for 2.0～5.0:1 again One step, preferably 2.0:1.
Further, described tert-butyl alcohol lithium and the ratio of the amount of carbazole compound material are 1.2～3.0:1；Further, excellent Elect 1.2～1.5:1 as.
Further, described organic solvent is toluene, the mixture of dimethylbenzene, benzene or any ratio of two of which；Further, Preferred solvent is toluene.
Further, the addition of described organic solvent is calculated as 1～100ml/ with the amount of the material of carbazole compound mmol.
Reactant liquor Separation ＆ Purification method of the present invention is: after reaction terminates, adds saturation sulfurous acid in reactant liquor Sodium solution is quenched, and filters and fully washs insoluble matter with ethyl acetate, takes organic faciess anhydrous sodium sulfate drying, filter to take Filtrate, gained filtrate decompression is distilled off after solvent, separated with silica gel column chromatography or recrystallization obtain formula (i), formula (ii) or N- heteroaryl carbazole compound shown in formula (iii).
Compared with prior art, beneficial effects of the present invention are embodied in:
(1) make the alkali reaction time using tert-butyl alcohol lithium to greatly shorten, improve the efficiency of reaction；Heteroaryl halide can be reduced 1.1 times of the consumption of thing, the most as little as amount of carbazole compound material；
(2) reaction dissolvent need not carry out strict Non-aqueous processing, using anhydrous sodium sulfate drying；
(3) low in raw material price, reaction process and simple to operate, yield up to more than 90% and be suitable to prepare in a large number and work Industry, has broad application prospects；
(4) used catalyst not only can be Hydro-Giene (Water Science)., can also use more economic cuprous bromide or protochloride Copper, and the consumption of catalyst can be reduced to the 1% of the amount of carbazole compound material.
Specific embodiment
Below by specific embodiment, the invention will be further described, but protection scope of the present invention is not limited in This.
The preparation (Hydro-Giene (Water Science). makees catalyst) of the bromo- 9- of embodiment 1:2- (2- pyridine radicals) carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add 2- bromine carbazole (3.69g, 15.00mmol, 1.0eq), Hydro-Giene (Water Science). (286mg, 1.5mmol, 0.1eq), tert-butyl alcohol lithium (3.60g, 45.00mmol, 3.0eq), substitute nitrogen three times, be subsequently adding 2- bromopyridine (4.28ml, 45.00mmol, 3.0eq), 1- Methylimidazole. (595ul, 7.50mmol, 0.5eq) and toluene (56.6ml).Reactant mixture flows back 24.0 hours at 130 DEG C, tlc thin layer Chromatogram monitoring finishes to raw material 2- bromine carbazole reaction.Saturated sodium bisulfite solution 30ml is quenched, and filters, and ethyl acetate is fully washed Insoluble matter, separates the organic faciess in mother solution, and aqueous phase adopts 30ml ethyl acetate to extract 3 times, merges organic faciess, and anhydrous sodium sulfate is done Dry, filter, vacuum distillation removes solvent and excessive 2- bromopyridine, and gained crude product is passed through silica gel column chromatogram separating purification, drenches Lotion: petroleum ether/dichloromethane=1:1-0:1, obtain white solid 4.64g, yield 96%.
1h nmr(500mhz,cdcl3): δ 7.31-7.34 (m, 2h), 7.42 (dd, j=8.0,1.5hz, 1h), 7.44- 7.47 (m, 1h), 7.61 (d, j=8.5hz, 1h), 7.77 (d, j=8.0hz, 1h), 7.93-7.96 (m, 2h), 8.01 (d, j= 1.5hz, 1h), 8.08 (d, j=7.5hz, 1h), 8.73 (d, j=5.0,1.5hz, 1h).
The preparation (Hydro-Giene (Water Science). makees catalyst) of the bromo- 9- of embodiment 2:2- (2- pyridine radicals) carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add 2- bromine carbazole (3.69g, 15.00mmol, 1.0eq), Hydro-Giene (Water Science). (286mg, 1.5mmol, 0.1eq), tert-butyl alcohol lithium (2.40g, 30.00mmol, 2.0eq), substitute nitrogen three times, be subsequently adding 2- bromopyridine (1.71ml, 18.00mmol, 1.2eq), 1- Methylimidazole. (595ul, 7.50mmol, 0.5eq) and toluene (56.6ml).Reactant mixture flows back 24.0 hours at 130 DEG C, tlc thin layer Chromatogram monitoring finishes to raw material 2- bromine carbazole reaction.Saturated sodium bisulfite solution 30ml is quenched, and filters, and ethyl acetate is fully washed Wash insoluble matter, separate the organic faciess in mother solution, aqueous phase adopts 30ml ethyl acetate to extract 3 times, merges organic faciess, anhydrous sodium sulfate It is dried, filters, vacuum distillation removes solvent and excessive 2- bromopyridine, and gained crude product is passed through silica gel column chromatogram separating purification, Eluent: petroleum ether/dichloromethane=1:1-0:1, obtain white solid 4.74g, yield 98%.
1h nmr(500mhz,cdcl3): δ 7.31-7.34 (m, 2h), 7.42 (dd, j=8.0,1.5hz, 1h), 7.44- 7.47 (m, 1h), 7.61 (d, j=8.5hz, 1h), 7.77 (d, j=8.0hz, 1h), 7.93-7.96 (m, 2h), 8.01 (d, j= 1.5hz, 1h), 8.08 (d, j=7.5hz, 1h), 8.73 (d, j=5.0,1.5hz, 1h).
The preparation (Hydro-Giene (Water Science). makees catalyst) of the bromo- 9- of embodiment 3:2- (2- pyridine radicals) carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add 2- bromine carbazole (3.69g, 15.00mmol, 1.0eq), Hydro-Giene (Water Science). (286mg, 1.5mmol, 0.1eq), tert-butyl alcohol lithium (2.40g, 30.00mmol, 2.0eq), substitute nitrogen three times, be subsequently adding 2- bromopyridine (1.71ml, 18.00mmol, 1.2eq), 1- Methylimidazole. (298ul, 3.75mmol, 0.25eq) and toluene (56.6ml).Reactant mixture flows back 24.0 hours at 130 DEG C, tlc thin layer Chromatogram monitoring finishes to raw material 2- bromine carbazole reaction.Saturated sodium bisulfite solution 30ml is quenched, and filters, and ethyl acetate is fully washed Insoluble matter, separates the organic faciess in mother solution, and aqueous phase adopts 30ml ethyl acetate to extract 3 times, merges organic faciess, and anhydrous sodium sulfate is done Dry, filter, vacuum distillation removes solvent and excessive 2- bromopyridine, and gained crude product is passed through silica gel column chromatogram separating purification, drenches Lotion: petroleum ether/dichloromethane=1:1-0:1, obtain white solid 4.79g, yield 99%.
1h nmr(500mhz,cdcl3): δ 7.31-7.34 (m, 2h), 7.42 (dd, j=8.0,1.5hz, 1h), 7.44- 7.47 (m, 1h), 7.61 (d, j=8.5hz, 1h), 7.77 (d, j=8.0hz, 1h), 7.93-7.96 (m, 2h), 8.01 (d, j= 1.5hz, 1h), 8.08 (d, j=7.5hz, 1h), 8.73 (d, j=5.0,1.5hz, 1h).
The preparation (Hydro-Giene (Water Science). makees catalyst) of the bromo- 9- of embodiment 4:2- (2- pyridine radicals) carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add 2- bromine carbazole (3.69g, 15.00mmol, 1.0eq), Hydro-Giene (Water Science). (143mg, 0.75mmol, 0.05eq), the tert-butyl alcohol lithium (2.40g, 30.00mmol, 2.0 Eq), substitute nitrogen three times, be subsequently adding 2- bromopyridine (1.71ml, 18.00mmol, 1.2eq), 1- Methylimidazole. (119ul, 1.50mmol, 0.10eq) and toluene (56.6ml).Reactant mixture flows back 1.2 hours at 130 DEG C, and tlc thin layer chromatography is monitored Finish to raw material 2- bromine carbazole reaction.Saturated sodium bisulfite solution 30ml is quenched, and filters, and ethyl acetate fully washs insoluble matter, Separate the organic faciess in mother solution, aqueous phase adopts 30ml ethyl acetate to extract 3 times, merges organic faciess, anhydrous sodium sulfate drying, mistake Filter, vacuum distillation removes solvent and excessive 2- bromopyridine, gained crude product is passed through silica gel column chromatogram separating purification, eluent: Petroleum ether/dichloromethane=1:1-0:1, obtains white solid 4.40g, yield 91%.
1h nmr(500mhz,cdcl3): δ 7.31-7.34 (m, 2h), 7.42 (dd, j=8.0,1.5hz, 1h), 7.44- 7.47 (m, 1h), 7.61 (d, j=8.5hz, 1h), 7.77 (d, j=8.0hz, 1h), 7.93-7.96 (m, 2h), 8.01 (d, j= 1.5hz, 1h), 8.08 (d, j=7.5hz, 1h), 8.73 (d, j=5.0,1.5hz, 1h).
The preparation (Hydro-Giene (Water Science). makees catalyst) of the bromo- 9- of embodiment 5:2- (2- pyridine radicals) carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add 2- bromine carbazole (3.69g, 15.00mmol, 1.0eq), Hydro-Giene (Water Science). (57mg, 0.30mmol, 0.02eq), tert-butyl alcohol lithium (2.40g, 30.00mmol, 2.0eq), substitute nitrogen three times, be subsequently adding 2- bromopyridine (1.71ml, 18.00mmol, 1.2eq), 1- Methylimidazole. (48ul, 0.60mmol, 0.04eq) and toluene (56.6ml).Reactant mixture flows back 2.7 hours at 130 DEG C, and tlc thin layer chromatography is monitored Finish to raw material 2- bromine carbazole reaction.Saturated sodium bisulfite solution 30ml is quenched, and filters, and ethyl acetate fully washs insoluble matter, Separate the organic faciess in mother solution, aqueous phase adopts 30ml ethyl acetate to extract 3 times, merges organic faciess, anhydrous sodium sulfate drying, mistake Filter, vacuum distillation removes solvent and excessive 2- bromopyridine, gained crude product is passed through silica gel column chromatogram separating purification, eluent: Petroleum ether/dichloromethane=1:1-0:1, obtains white solid 4.79g, yield 99%.
1h nmr(500mhz,cdcl3): δ 7.31-7.34 (m, 2h), 7.42 (dd, j=8.0,1.5hz, 1h), 7.44- 7.47 (m, 1h), 7.61 (d, j=8.5hz, 1h), 7.77 (d, j=8.0hz, 1h), 7.93-7.96 (m, 2h), 8.01 (d, j= 1.5hz, 1h), 8.08 (d, j=7.5hz, 1h), 8.73 (d, j=5.0,1.5hz, 1h).
The preparation (Hydro-Giene (Water Science). makees catalyst) of the bromo- 9- of embodiment 6:2- (2- pyridine radicals) carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add 2- bromine carbazole (3.69g, 15.00mmol, 1.0eq), Hydro-Giene (Water Science). (29mg, 0.15mmol, 0.01eq), tert-butyl alcohol lithium (2.40g, 30.00mmol, 2.0eq), substitute nitrogen three times, be subsequently adding 2- bromopyridine (1.71ml, 18.00mmol, 1.2eq), 1- Methylimidazole. (24ul, 0.30mmol, 0.02eq) and toluene (56.6ml).Reactant mixture flows back 4.0 hours at 130 DEG C, and tlc thin layer chromatography is monitored Finish to raw material 2- bromine carbazole reaction.Saturated sodium bisulfite solution 30ml is quenched, and filters, and ethyl acetate fully washs insoluble matter, Separate the organic faciess in mother solution, aqueous phase adopts 30ml ethyl acetate to extract 3 times, merges organic faciess, anhydrous sodium sulfate drying, mistake Filter, vacuum distillation removes solvent and excessive 2- bromopyridine, gained crude product is passed through silica gel column chromatogram separating purification, eluent: Petroleum ether/dichloromethane=1:1-0:1, obtains white solid 4.74g, yield 98%.
1h nmr(500mhz,cdcl3): δ 7.31-7.34 (m, 2h), 7.42 (dd, j=8.0,1.5hz, 1h), 7.44- 7.47 (m, 1h), 7.61 (d, j=8.5hz, 1h), 7.77 (d, j=8.0hz, 1h), 7.93-7.96 (m, 2h), 8.01 (d, j= 1.5hz, 1h), 8.08 (d, j=7.5hz, 1h), 8.73 (d, j=5.0,1.5hz, 1h).
The preparation (Hydro-Giene (Water Science). makees catalyst) of the bromo- 9- of embodiment 7:2- (2- pyridine radicals) carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add 2- bromine carbazole (3.69g, 15.00mmol, 1.0eq), Hydro-Giene (Water Science). (29mg, 0.15mmol, 0.01eq), tert-butyl alcohol lithium (1.80g, 22.50mmol, 1.5eq), substitute nitrogen three times, be subsequently adding 2- bromopyridine (1.57ml, 16.50mmol, 1.1eq), 1- Methylimidazole. (24ul, 0.30mmol, 0.02eq) and toluene (56.6ml).Reactant mixture flows back 5.5 hours at 130 DEG C, and tlc thin layer chromatography is monitored Finish to raw material 2- bromine carbazole reaction.Saturated sodium bisulfite solution 30ml is quenched, and filters, and ethyl acetate fully washs insoluble matter, Separate the organic faciess in mother solution, aqueous phase adopts 30ml ethyl acetate to extract 3 times, merges organic faciess, anhydrous sodium sulfate drying, mistake Filter, vacuum distillation removes solvent and excessive 2- bromopyridine, gained crude product is passed through silica gel column chromatogram separating purification, eluent: Petroleum ether/dichloromethane=1:1-0:1, obtains white solid 4.79g, yield 99%.
1h nmr(500mhz,cdcl3): δ 7.31-7.34 (m, 2h), 7.42 (dd, j=8.0,1.5hz, 1h), 7.44- 7.47 (m, 1h), 7.61 (d, j=8.5hz, 1h), 7.77 (d, j=8.0hz, 1h), 7.93-7.96 (m, 2h), 8.01 (d, j =1.5hz, 1h), 8.08 (d, j=7.5hz, 1h), 8.73 (d, j=5.0,1.5hz, 1h).
The preparation (Hydro-Giene (Water Science). makees catalyst) of the bromo- 9- of embodiment 8:2- (2- pyridine radicals) carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add 2- bromine carbazole (3.69g, 15.00mmol, 1.0eq), Hydro-Giene (Water Science). (29mg, 0.15mmol, 0.01eq), tert-butyl alcohol lithium (1.44g, 18.00mmol, 1.2eq), substitute nitrogen three times, be subsequently adding 2- bromopyridine (1.57ml, 16.50mmol, 1.1eq), 1- Methylimidazole. (24ul, 0.30mmol, 0.02eq) and toluene (56.6ml).Reactant mixture flows back 9.5 hours at 130 DEG C, and tlc thin layer chromatography is monitored Finish to raw material 2- bromine carbazole reaction.Saturated sodium bisulfite solution 30ml is quenched, and filters, and ethyl acetate fully washs insoluble matter, Separate the organic faciess in mother solution, aqueous phase adopts 30ml ethyl acetate to extract 3 times, merges organic faciess, anhydrous sodium sulfate drying, mistake Filter, vacuum distillation removes solvent and excessive 2- bromopyridine, gained crude product is passed through silica gel column chromatogram separating purification, eluent: Petroleum ether/dichloromethane=1:1-0:1, obtains white solid 4.79g, yield 99%.
1h nmr(500mhz,cdcl3): δ 7.31-7.34 (m, 2h), 7.42 (dd, j=8.0,1.5hz, 1h), 7.44- 7.47 (m, 1h), 7.61 (d, j=8.5hz, 1h), 7.77 (d, j=8.0hz, 1h), 7.93-7.96 (m, 2h), 8.01 (d, j= 1.5hz, 1h), 8.08 (d, j=7.5hz, 1h), 8.73 (d, j=5.0,1.5hz, 1h).
The preparation (Hydro-Giene (Water Science). makees catalyst) of the bromo- 9- of embodiment 9:2- (2- pyridine radicals) carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add 2- bromine carbazole (3.69g, 15.00mmol, 1.0eq), Hydro-Giene (Water Science). (29mg, 0.15mmol, 0.01eq), tert-butyl alcohol lithium (1.80g, 22.50mmol, 1.5eq), substitute nitrogen three times, be subsequently adding 2- bromopyridine (1.57ml, 16.50mmol, 1.1eq), 1- Methylimidazole. (24ul, 0.30mmol, 0.02eq) and toluene (56.6ml).Reactant mixture flows back 11.0 hours at 110 DEG C, and tlc thin layer chromatography is supervised Survey and finish to raw material 2- bromine carbazole reaction.Saturated sodium bisulfite solution 30ml is quenched, and filters, ethyl acetate is fully washed insoluble Thing, separates the organic faciess in mother solution, and aqueous phase adopts 30ml ethyl acetate to extract 3 times, merging organic faciess, anhydrous sodium sulfate drying, Filter, vacuum distillation removes solvent and excessive 2- bromopyridine, and gained crude product is passed through silica gel column chromatogram separating purification, drip washing Agent: petroleum ether/dichloromethane=1:1-0:1, obtain white solid 4.69g, yield 97%.
1h nmr(500mhz,cdcl3): δ 7.31-7.34 (m, 2h), 7.42 (dd, j=8.0,1.5hz, 1h), 7.44- 7.47 (m, 1h), 7.61 (d, j=8.5hz, 1h), 7.77 (d, j=8.0hz, 1h), 7.93-7.96 (m, 2h), 8.01 (d, j= 1.5hz, 1h), 8.08 (d, j=7.5hz, 1h), 8.73 (d, j=5.0,1.5hz, 1h).
The preparation (Cu-lyt. makees catalyst) of the bromo- 9- of embodiment 10:2- (2- pyridine radicals) carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add 2- bromine carbazole (492.2mg, 2.00mmol, 1.0eq), Cu-lyt. (2.0mg, 0.02mmol, 0.01eq), tert-butyl alcohol lithium (240.2mg, 3.00mmol, 1.5eq), substitute nitrogen three times, be subsequently adding 2- bromopyridine (209.8ul, 2.20mmol, 1.1eq), 1- Methylimidazole. (3.2ul, 0.04mmol, 0.02eq) and toluene (7.6ml).Reactant mixture flows back 2.6 hours at 130 DEG C, tlc thin layer color Spectrum monitoring finishes to raw material 2- bromine carbazole reaction.Saturated sodium bisulfite solution 5ml is quenched, and filters, and ethyl acetate is fully washed not Molten thing, separates the organic faciess in mother solution, anhydrous sodium sulfate drying, filters, and vacuum distillation removes solvent and excessive 2- bromopyridine, Gained crude product is passed through silica gel column chromatogram separating purification, eluent: petroleum ether/dichloromethane=1:1-0:1, obtain white solid 600.8mg, yield 93%.
1h nmr(500mhz,cdcl3): δ 7.31-7.34 (m, 2h), 7.42 (dd, j=8.0,1.5hz, 1h), 7.44- 7.47 (m, 1h), 7.61 (d, j=8.5hz, 1h), 7.77 (d, j=8.0hz, 1h), 7.93-7.96 (m, 2h), 8.01 (d, j= 1.5hz, 1h), 8.08 (d, j=7.5hz, 1h), 8.73 (d, j=5.0,1.5hz, 1h).
The preparation (cuprous bromide makees catalyst) of the bromo- 9- of embodiment 11:2- (2- pyridine radicals) carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add 2- bromine carbazole (492.2mg, 2.00mmol, 1.0eq), cuprous bromide (2.9mg, 0.02mmol, 0.01eq), tert-butyl alcohol lithium (240.2mg, 3.00mmol, 1.5eq), substitute nitrogen three times, be subsequently adding 2- bromopyridine (209.8ul, 2.20mmol, 1.1eq), 1- Methylimidazole. (3.2 Ul, 0.04mmol, 0.02eq) and toluene (7.6ml).Reactant mixture flows back 2.6 hours at 130 DEG C, and tlc thin layer chromatography is supervised Survey and finish to raw material 2- bromine carbazole reaction.Saturated sodium bisulfite solution 5ml is quenched, and filters, and ethyl acetate fully washs insoluble matter, Separate the organic faciess in mother solution, anhydrous sodium sulfate drying, filter, vacuum distillation removes solvent and excessive 2- bromopyridine, by institute Obtain crude product and pass through silica gel column chromatogram separating purification, eluent: petroleum ether/dichloromethane=1:1-0:1, obtain white solid 615.3mg, yield 95%.
1h nmr(500mhz,cdcl3): δ 7.31-7.34 (m, 2h), 7.42 (dd, j=8.0,1.5hz, 1h), 7.44- 7.47 (m, 1h), 7.61 (d, j=8.5hz, 1h), 7.77 (d, j=8.0hz, 1h), 7.93-7.96 (m, 2h), 8.01 (d, j= 1.5hz, 1h), 8.08 (d, j=7.5hz, 1h), 8.73 (d, j=5.0,1.5hz, 1h).
The preparation (Cu-lyt. makees catalyst) of the bromo- 9- of embodiment 12:2- (2- pyridine radicals) carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add 2- bromine carbazole (3.69g, 15.00mmol, 1.0eq), Cu-lyt. (14.9mg, 0.15mmol, 0.01eq), tert-butyl alcohol lithium (1.80g, 22.50mmol, 1.5eq), substitute nitrogen three times, be subsequently adding 2- bromopyridine (1.57ml, 16.50mmol, 1.1eq), 1- Methylimidazole. (23.78ul, 0.30mmol, 0.02eq) and toluene (56.6ml).Reactant mixture flows back 4.9 hours at 130 DEG C, and tlc is thin Layer chromatography is monitored and is finished to raw material 2- bromine carbazole reaction.Saturated sodium bisulfite solution 30ml is quenched, and filters, and ethyl acetate is fully washed Wash insoluble matter, separate the organic faciess in mother solution, aqueous phase adopts 30ml ethyl acetate to extract 3 times, merges organic faciess, anhydrous sodium sulfate It is dried, filters, vacuum distillation removes solvent and excessive 2- bromopyridine, and gained crude product is passed through silica gel column chromatogram separating purification, Eluent: petroleum ether/dichloromethane=1:1-0:1, obtain white solid 4.70g, yield 97%.
1h nmr(500mhz,cdcl3): δ 7.31-7.34 (m, 2h), 7.42 (dd, j=8.0,1.5hz, 1h), 7.44- 7.47 (m, 1h), 7.61 (d, j=8.5hz, 1h), 7.77 (d, j=8.0hz, 1h), 7.93-7.96 (m, 2h), 8.01 (d, j= 1.5hz, 1h), 8.08 (d, j=7.5hz, 1h), 8.73 (d, j=5.0,1.5hz, 1h).
The preparation (cuprous bromide makees catalyst) of the bromo- 9- of embodiment 13:2- (2- pyridine radicals) carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add 2- bromine carbazole (3.69g, 15.00mmol, 1.0eq), cuprous bromide (21.5mg, 0.15mmol, 0.01eq), tert-butyl alcohol lithium (1.80g, 22.50mmol, 1.5eq), substitute nitrogen three times, be subsequently adding 2- bromopyridine (1.57ml, 16.50mmol, 1.1eq), 1- Methylimidazole. (23.8ul, 0.30mmol, 0.02eq) and toluene (56.6ml).Reactant mixture flows back 5.4 hours at 130 DEG C, tlc thin layer Chromatogram monitoring finishes to raw material 2- bromine carbazole reaction.Saturated sodium bisulfite solution 30ml is quenched, and filters, and ethyl acetate is fully washed Insoluble matter, separates the organic faciess in mother solution, and aqueous phase adopts 30ml ethyl acetate to extract 3 times, merges organic faciess, and anhydrous sodium sulfate is done Dry, filter, vacuum distillation removes solvent and excessive 2- bromopyridine, and gained crude product is passed through silica gel column chromatogram separating purification, drenches Lotion: petroleum ether/dichloromethane=1:1-0:1, obtain white solid 4.55g, yield 94%.
1h nmr(500mhz,cdcl3): δ 7.31-7.34 (m, 2h), 7.42 (dd, j=8.0,1.5hz, 1h), 7.44- 7.47 (m, 1h), 7.61 (d, j=8.5hz, 1h), 7.77 (d, j=8.0hz, 1h), 7.93-7.96 (m, 2h), 8.01 (d, j= 1.5hz, 1h), 8.08 (d, j=7.5hz, 1h), 8.73 (d, j=5.0,1.5hz, 1h).
The preparation of the bromo- 9- of embodiment 14:2- (3- methyl -2- pyridine radicals) carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add 2- bromine carbazole (492.2mg, 2.00mmol, 1.0eq), Cu-lyt. (2.0mg, 0.02mmol, 0.01eq), tert-butyl alcohol lithium (240.2mg, 3.00mmol, 1.5eq), substitute nitrogen three times, be subsequently adding 3- methyl -2- bromopyridine (334.2ul, 3.00mmol, 1.5eq), 1- methyl miaow Azoles (3.2ul, 0.04mmol, 0.02eq) and toluene (7.6ml).Reactant mixture flows back 2.5 hours at 130 DEG C, tlc thin layer Chromatogram monitoring finishes to raw material 2- bromine carbazole reaction.Saturated sodium bisulfite solution 5ml is quenched, and filters, and ethyl acetate is fully washed Insoluble matter, separates the organic faciess in mother solution, anhydrous sodium sulfate drying, filters, vacuum distillation removes solvent, and gained crude product is passed through Silica gel column chromatogram separating purification, eluent: petrol ether/ethyl acetate=40:1-1:1, obtain white solid 611.9mg, yield 91%.
1h nmr(500mhz,cdcl3): δ 2.08 (s, 3h), 7.08 (d, j=8.0hz, 1h), 7.25-7.31 (m, 2h), 7.38-7.41 (m, 3h), 7.83 (dd, j=7.5,1.0hz, 1h), 7.98 (d, j=8.0hz, 1h), 8.10 (d, j=7.5hz, 1h), 8.58 (dd, j=5.0,1.5hz, 1h).13c nmr(125mhz,cdcl3):δ17.38,110.31,113.24, 119.54,120.38,120.54,121.51,122.49,122.88,123.27,123.94,126.42,131.52,140.34, 140.70,141.01,147.94,149.12.
The preparation of the bromo- 9- of embodiment 15:2- (4- methyl -2- pyridine radicals) carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add 2- bromine carbazole (492.2mg, 2.00mmol, 1.0eq), Cu-lyt. (2.0mg, 0.02mmol, 0.01eq), tert-butyl alcohol lithium (240.2mg, 3.00mmol, 1.5eq), substitute nitrogen three times, be subsequently adding 4- methyl -2- bromopyridine (334.0ul, 3.00mmol, 1.5eq), 1- methyl miaow Azoles (3.2ul, 0.04mmol, 0.02eq) and toluene (7.6ml).Reactant mixture flows back 2.5 hours at 130 DEG C, tlc thin layer Chromatogram monitoring finishes to raw material 2- bromine carbazole reaction.Saturated sodium bisulfite solution 5ml is quenched, and filters, and ethyl acetate is fully washed Insoluble matter, separates the organic faciess in mother solution, anhydrous sodium sulfate drying, filters, vacuum distillation removes solvent, and gained crude product is passed through Silica gel column chromatogram separating purification, eluent: petroleum ether/dichloromethane=10:1-1:1, obtain white solid 643.2mg, yield 95%.
1h nmr(500mhz,cdcl3): δ 2.47 (s, 3h), 7.13 (d, j=5.0hz, 1h), 7.30 (t, j=8.0hz, 1h), 7.39-7.46 (m, 3h), 7.72 (d, j=8.0hz, 1h), 7.93 (d, j=8.0hz, 1h), 7.97 (d, j=1.5hz, 1h), 8.06 (d, j=7.5hz, 1h), 8.56 (d, j=5.0hz, 1h).13c nmr(125mhz,cdcl3):δ21.20, 111.08,114.33,119.67,119.69,120.16,121.12,121.20,122.87,123.05,123.54,123.88, 126.48,139.69,140.40,149.37,150.23,151.26.
The preparation of the bromo- 9- of embodiment 16:2- (5- methyl -2- pyridine radicals) carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add 2- bromine carbazole (492.2mg, 2.00mmol, 1.0eq), 5- methyl -2- bromopyridine (516.1mg, 3.00mmol, 1.5eq), Cu-lyt. (2.0mg, 0.02mmol, 0.01eq), tert-butyl alcohol lithium (240.2mg, 3.00mmol, 1.5eq), substitute nitrogen three times, be subsequently adding 1- methyl Imidazoles (3.2ul, 0.04mmol, 0.02eq) and toluene (7.6ml).Reactant mixture flows back 3 hours at 130 DEG C, and tlc is thin Layer chromatography is monitored and is finished to raw material 2- bromine carbazole reaction.Saturated sodium bisulfite solution 5ml is quenched, and filters, and ethyl acetate is fully washed Wash insoluble matter, separate the organic faciess in mother solution, anhydrous sodium sulfate drying, filter, vacuum distillation removes solvent, and gained crude product is led to Cross silica gel column chromatogram separating purification, eluent: petroleum ether/dichloromethane=10:1-1:1, obtain white solid 617.1mg, yield 92%.
1h nmr(500mhz,cdcl3): δ 2.44 (s, 3h), 7.30 (t, j=7.5hz, 1h), 7.41 (dd, j=8.0, 1.5hz, 1h), 7.42-7.45 (m, 1h), 7.47 (d, j=8.0hz, 1h), 7.70 (d, j=8.5hz, 1h), 7.72 (dd, j= 8.5,2.5hz, 1h), 7.93 (s, 1h), 7.94 (d, j=6.0hz, 1h), 8.06 (d, j=8.0hz, 1h), 8.54 (d, j= 1.5hz,1h).13c nmr(125mhz,cdcl3):δ18.03,110.95,114.16,118.66,119.68,120.17, 121.03,121.22,122.96,123.45,123.78,126.48,131.48,139.19,139.77,140.46,148.80, 149.92.
The preparation of the bromo- 9- of embodiment 17:2- (5- bromo-2-pyridyl base) carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add 2- bromine carbazole (246.1mg, 1.0mmol, 1.0eq), Cu-lyt. (1.0mg, 0.01mmol, 0.01eq), tert-butyl alcohol lithium (120.1mg, 1.5mmol, 1.5eq), substitute nitrogen three times, be subsequently adding 2,5- dibromo pyridine (355.3mg, 1.5mmol, 1.5eq), 1- Methylimidazole. (1.6ul, 0.02mmol, 0.02eq) and toluene (4ml).Reactant mixture flows back 5.0 hours at 130 DEG C, tlc thin layer chromatography Monitor and finish to raw material 2- bromine carbazole reaction.Saturated sodium bisulfite solution is quenched, and filters, and ethyl acetate fully washs insoluble matter, Separate the organic faciess in mother solution, anhydrous sodium sulfate drying, filter, vacuum distillation removes solvent and excessive 2,5- dibromo pyridine, Gained crude product is passed through silica gel column chromatogram separating purification, eluent: petroleum ether/dichloromethane=1:1, obtain white solid 397.8mg, yield 98%.
1h nmr(500mhz,cdcl3): δ 7.33 (t, j=7.5hz, 1h), 7.42 (dd, j=8.5,1.5hz, 1h), 7.46 (d, j=7.5hz, 1h), 7.50 (d, j=8.5hz, 1h), 7.73 (d, j=8.0hz, 1h), 7.93 (d, j=8.0hz, 1h), 7.98 (d, j=1.5hz, 1h), 8.01 (dd, j=8.5,2.5hz, 1h), 8.05 (d, j=7.5hz, 1h), 8.75 (d, j =2.0hz, 1h).13c nmr(125mhz,cdcl3): δ 111.03,114.37,117.38,119.88,119.92,120.30, 121.30,121.64,123.30,123.81,124.42, 126.73,139.28,139.99,141.19,149.87, 150.70.
The preparation of the bromo- 9- of embodiment 18:2- (4- fluoro- 2- pyridine radicals) carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add 2- bromine carbazole (246.1mg, 1.00mmol, 1.0eq), Cu-lyt. (1.0mg, 0.01mmol, 0.01eq), tert-butyl alcohol lithium (120.1mg, 1.50mmol, 1.5eq), substitute nitrogen three times, be subsequently adding 4- fluoro- 2- bromopyridine (155.0ul, 1.50mmol, 1.5eq), 1- Methylimidazole. (1.6ul, 0.02mmol, 0.02eq) and toluene (3.8ml).Reactant mixture flows back 4.0 hours at 130 DEG C, tlc thin layer color Spectrum monitoring finishes to raw material 2- bromine carbazole reaction.Saturated sodium bisulfite solution 3ml is quenched, and filters, and ethyl acetate is fully washed not Molten thing, separates the organic faciess in mother solution, anhydrous sodium sulfate drying, filters, vacuum distillation removes solvent, gained crude product is passed through silicon Glue column chromatography separating purification, eluent: petroleum ether/dichloromethane=5:1-1:1, obtain white solid 319.1mg, yield 93%.
1h nmr(500mhz,cdcl3): δ 7.05-7.08 (m, 1h), 7.32-7.36 (m, 2h), 7.44 (dd, j=8.0, 1.5hz, 1h), 7.45-7.48 (m, 1h), 7.80 (d, j=8.5hz, 1h), 7.93 (d, j=8.5hz, 1h), 8.05 (d, j= 8.0hz, 1h), 8.08 (d, j=1.5hz, 1h), 8.66-8.69 (m, 1h).13c nmr(125mhz,cdcl3): δ 106.33 (d, ), j=20.0hz 109.66 (d, j=17.4hz), 111.18,114.67,119.96,120.28,121.24,121.76, (123.37,123.91,124.56,126.76,139.59 d, j=98.75hz), 151.75 (d, j=8.8hz), 153.50 (d, ), j=10.0hz 168.89,170.98.
The preparation of the bromo- 9- of embodiment 19:2- (2- pyrimidine radicals) carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add 2- bromine carbazole (492.2mg, 2.00mmol, 1.0eq), 2- Bromopyrimidine (476.9mg, 3.00mmol, 1.5eq), Cu-lyt. (2.0mg, 0.02mmol, 0.01eq), tert-butyl alcohol lithium (240.2mg, 3.00mmol, 1.5eq), substitutes nitrogen three times, is subsequently adding 1- Methylimidazole. (3.2 Ul, 0.04mmol, 0.02eq) and toluene (7.6ml).Reactant mixture flows back 7.0 hours at 130 DEG C, and tlc thin layer chromatography is supervised Survey and finish to raw material 2- bromine carbazole reaction.Saturated sodium bisulfite solution 5ml is quenched, and filters, and ethyl acetate fully washs insoluble matter, Separate the organic faciess in mother solution, anhydrous sodium sulfate drying, filter, vacuum distillation removes solvent, gained crude product is passed through silicagel column Chromatographic separation and purification, eluent: petroleum ether/dichloromethane=5:1-1:1, obtain white solid 621.7mg, yield 96%.
1h nmr(500mhz,cdcl3): δ 7.09 (t, j=4.5hz, 1h), 7.35 (t, j=7.5hz, 1h), 7.46 (dd, J=8.0,1.5hz, 1h), 7.48-7.52 (m, 1h), 7.87 (d, j=8.0hz, 1h), 7.99 (d, j=7.5hz, 1h), 8.80 (d, j=4.5hz, 2h), 8.82 (d, j=8.5hz, 1h), 9.06 (d, j=2.0hz, 1h)；13c nmr(125mhz,cdcl3): δ116.23,116.51,119.42,119.45,120.09,120.43,122.57,124.68,125.00,125.35, 126.95,139.18,139.71,157.83,158.81.
The preparation of the bromo- 9- of embodiment 20:2- (2- pyrazinyl) carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add 2- bromine carbazole (246.1mg, 1.00mmol, 1.0eq), Cu-lyt. (1.0mg, 0.01mmol, 0.01eq), tert-butyl alcohol lithium (120.1mg, 1.50mmol, 1.5eq), substitute nitrogen three times, be subsequently adding 2- bromo-pyrazine (135.7ul, 1.50mmol, 1.5eq), 1- Methylimidazole. (1.6ul, 0.02mmol, 0.02eq) and toluene (3.8ml).Reactant mixture flows back 7.0 hours at 130 DEG C, tlc thin layer color Spectrum monitoring finishes to raw material 2- bromine carbazole reaction.Saturated sodium bisulfite solution 5ml is quenched, and filters, and ethyl acetate is fully washed not Molten thing, separates the organic faciess in mother solution, anhydrous sodium sulfate drying, filters, and vacuum distillation removes solvent and excessive 2- bromo-pyrazine, Gained crude product is passed through silica gel column chromatogram separating purification, eluent: petroleum ether/dichloromethane=5:1-1:1, obtain white solid 300.6mg, yield 93%.
1h nmr(500mhz,cdcl3): δ 7.35 (t, j=7.0hz, 1h), 7.43-7.49 (m, 2h), 7.80 (d, j= 8.0hz, 1h), 7.92 (d, j=8.0hz, 1h), 8.05 (d, j=5.0hz, 1h), 8.06 (s, 1h), 8.56 (d, j=2.5hz, 1h), 8.67 (dd, j=2.0,1.5hz, 1h), 9.01 (d, j=1.5hz, 1h).13c nmr(125mhz,cdcl3):δ 110.94,114.44,120.06,120.38,121.34,122.10,123.61,124.08,124.91,126.90,139.01, 139.79,140.51,141.54,143.54,148.25.
The preparation of the bromo- 9- of embodiment 21:2- (2- quinolyl) carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add 2- bromine carbazole (246.1mg, 1.00mmol, 1.0eq), 2- bromoquinoline (312.1mg, 1.50mmol, 1.5eq), Cu-lyt. (1.0mg, 0.01mmol, 0.01eq), tert-butyl alcohol lithium (120.1mg, 1.50mmol, 1.5eq), substitutes nitrogen three times, is subsequently adding 1- Methylimidazole. (1.6ul, 0.02mmol, 0.02eq) and toluene (3.8ml).Reactant mixture flows back 3.0 hours at 130 DEG C, tlc thin layer color Spectrum monitoring finishes to raw material 2- bromine carbazole reaction.Saturated sodium bisulfite solution 5ml is quenched, and filters, and ethyl acetate is fully washed not Molten thing, separates the organic faciess in mother solution, anhydrous sodium sulfate drying, filters, vacuum distillation removes solvent, gained crude product is passed through silicon Glue column chromatography separating purification, eluent: petroleum ether/dichloromethane=5:1-3:1, obtain white solid 351.6mg, yield 94%.
1h nmr(500mhz,cdcl3): δ 7.34 (t, j=7.5hz, 1h), 7.42-7.48 (m, 2h), 7.60 (td, j= 7.5,1.0hz, 1h), 7.74 (d, j=9.0hz, 1h), 7.78-7.81 (m, 1h), 7.91 (t, j=8.5hz, 2h), 7.96 (d, J=8.0hz, 1h), 8.08 (d, j=7.5hz, 1h), 8.17 (d, j=8.5hz, 1h), 8.18 (d, j=1.5hz, 1h), 8.35 (d, j=8.5hz, 1h).13c nmr(125mhz,cdcl3):δ111.51,114.77,117.48,119.87,120.25, 121.27,121.57,123.43,123.90,124.34,126.59,126.61,126.68,127.63,128.82,130.48, 139.00,139.60,140.31,147.65,150.27.
The preparation of the bromo- 9- of embodiment 22:2- (1- isoquinolyl) carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add 2- bromine carbazole (626.2mg, 2.54mmol, 1.0eq), 1- chlorine isoquinolin (624.2mg, 3.82mmol, 1.5eq), Cu-lyt. (5.0mg, 0.05mmol, 0.02eq), tert-butyl alcohol lithium (305.0mg, 3.82mmol, 1.5eq), substitutes nitrogen three times, is subsequently adding 1- Methylimidazole. (8.2ul, 0.10mmol, 0.04eq) and toluene (9.7ml).Reactant mixture flows back 5 days at 130 DEG C, tlc during reaction Thin layer chromatography monitors raw material 2- bromine carbazole.Saturated sodium bisulfite solution 5ml is quenched, and filters, and ethyl acetate fully washs insoluble matter, Separate the organic faciess in mother solution, anhydrous sodium sulfate drying, filter, vacuum distillation removes solvent, gained crude product is passed through silicagel column Chromatographic separation and purification, eluent: petroleum ether/dichloromethane=10:1-1:1, obtain white solid 228.6mg, yield 24%.
1h nmr(500mhz,cdcl3): δ 7.09 (d, j=8.0hz, 1h), 7.30-7.38 (m, 3h), 7.42 (dd, j= 8.5,1.5hz, 1h), 7.50-7.53 (m, 1h), 7.63 (d, j=8.0hz, 1h), 7.77-7.80 (m, 1h), 7.86 (d, j= 5.5hz, 1h), 8.02 (d, j=8.5hz, 2h), 8.14 (d, j=8.0hz, 1h), 8.64 (d, j=5.5hz, 1h).13c nmr (126mhz,cdcl3): δ 111.11,114.02,119.61,120.31,120.92,121.45,121.63,122.90, 123.25,123.73,125.03,125.46,126.44,127.31,128.26,131.20,138.69,141.44,141.99, 142.26,149.58.
The preparation of embodiment 23:2- benzothiazolyl carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add 2- bromine carbazole (123.1mg, 0.5mmol, 1.0eq), Cu-lyt. (0.5mg, 0.005mmol, 0.01eq), tert-butyl alcohol lithium (60.0mg, 0.75mmol, 1.5eq), substitute nitrogen three times, be subsequently adding 2- bromo benzothiazole (160.6mg, 0.75mmol, 1.5eq), 1- Methylimidazole. (0.82ul, 0.01mmol, 0.02eq) and toluene (4ml).Reactant mixture flows back 48 hours at 130 DEG C, tlc thin layer chromatography Monitor and finish to raw material 2- bromine carbazole reaction.Saturated sodium bisulfite solution is quenched, and filters, and ethyl acetate fully washs insoluble matter, Separate the organic faciess in mother solution, anhydrous sodium sulfate drying, filter, vacuum distillation removes solvent and excessive 2- bromo benzothiazole, Gained crude product is passed through silica gel column chromatogram separating purification, eluent: petroleum ether/dichloromethane=1:1, obtain light yellow solid 58.5mg, yield 79%.
1h nmr(500mhz,cdcl3): δ 7.39-7.44 (m, 2h), 7.52 (dd, j=8.0,1.5hz, 1h), 7.54- 7.58 (m, 2h), 7.90 (d, j=8.5hz, 1h), 7.92 (d, j=8.0hz, 1h), 8.05 (d, j=7.5hz, 1h), 8.09 (d, j=8.0hz, 1h), 8.37 (d, j=8.5hz, 1h), 8.71 (d, j=1.5hz, 1h).13c nmr(125mhz, cdcl3):δ112.92,116.71,120.19,120.57,121.06,121.18,122.50,122.99,124.03, 124.56,124.86,125.92,126.72,127.34,132.06,139.14,139.98, 150.10,157.22.
The preparation of embodiment 24:2- bromo- (2- thiazolyl) carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add 2- bromine carbazole (492.2mg, 2.0mmol, 1.0eq), Hydro-Giene (Water Science). (3.8mg, 0.02mmol, 0.01eq), tert-butyl alcohol lithium (240.2mg, 3.0mmol, 1.5eq), substitute nitrogen three times, be subsequently adding 2- bromo thiazole (270.4mg, 3.0mmol, 1.5eq), 1- Methylimidazole. (3.3mg, 0.04mmol, 0.02eq) and toluene (8ml).Reactant mixture flows back 8 hours at 130 DEG C, and tlc thin layer chromatography is monitored to former Material 2- bromine carbazole reaction finishes.Saturated sodium bisulfite solution is quenched, and filters, and ethyl acetate is fully washed insoluble matter, separated mother solution In organic faciess, anhydrous sodium sulfate drying, filter, vacuum distillation removes solvent and excessive 2- bromo thiazole, and gained crude product is led to Cross silica gel column chromatogram separating purification, eluent: petroleum ether/dichloromethane=10:1, obtain white solid 606.5mg, yield 92%.
1h nmr(500mhz,cdcl3): δ 7.27 (d, j=4hz, 1h), 7.35-7.38 (m, 1h), 7.47 (dd, j= 1.5,8.0hz, 1h), 7.52 (td, j=1.0,7.0hz, 1h), 7.79 (d, j=3.5hz, 1h), 7.90 (d, j=8.5hz, 1h), 8.03 (d, j=8.0hz, 1h), 8.12 (d, j=8.5hz, 1h), 8.46 (d, j=1.5hz, 1h).13c nmr (125mhz,cdcl3):δ112.09,115.08,115.88,120.18,120.39,121.08,122.47,123.52, 124.10,125.37,127.17,139.25,140.00,140.10,158.47.
The preparation of the bromo- 9- of embodiment 25:3- (2- pyridine radicals) carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add 3- bromine carbazole (492.2mg, 2.00mmol, 1.0eq), Cu-lyt. (2.0mg, 0.02mmol, 0.01eq), tert-butyl alcohol lithium (240.2mg, 3.00mmol, 1.5eq), substitute nitrogen three times, be subsequently adding 2- bromopyridine (286.1ul, 3.00mmol, 1.5eq), 1- Methylimidazole. (3.2ul, 0.04mmol, 0.02eq) and toluene (7.6ml).Reactant mixture flows back 3.5 hours at 130 DEG C, tlc thin layer Chromatogram monitoring finishes to raw material 3- bromine carbazole reaction.Saturated sodium bisulfite solution 5ml is quenched, and filters, and ethyl acetate is fully washed Insoluble matter, separates the organic faciess in mother solution, anhydrous sodium sulfate drying, filters, vacuum distillation removes solvent, and gained crude product is passed through Silica gel column chromatogram separating purification, eluent: petroleum ether/dichloromethane=3:1-1:1, obtain white solid 613.7mg, yield 95%.
1h nmr(500mhz,cdcl3): δ 7.29-7.33 (m, 2h), 7.45 (t, j=8.0hz, 1h), 7.50 (dd, j= 8.5,2.0hz, 1h), 7.58 (d, j=8.0hz, 1h), 7.72 (d, j=9.0hz, 1h), 7.79 (d, j=8.5hz, 1h), 7.91 (td, j=7.5,1.5hz, 1h), 8.05 (d, j=8.0hz, 1h), 8.21 (d, j=2.0hz, 1h), 8.71 (dd, j= 4.5,1.5hz,1h).13c nmr(125mhz,cdcl3):δ111.18,112.76,113.67,118.92,120.36, 121.23,121.47,122.89,123.15,126.03,126.89,128.81,138.22,138.55,139.76,149.67, 151.38.
The preparation of the bromo- 9- of embodiment 26:2,7- bis- (2- pyridine radicals) carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add 2,7- dibromo carbazole (325.0mg, 1.00mmol, 1.0eq), Cu-lyt. (1.0mg, 0.01mmol, 0.01eq), tert-butyl alcohol lithium (120.1mg, 1.50mmol, 1.5eq), substitute nitrogen three times, be subsequently adding 2- bromopyridine (143.0ul, 1.50mmol, 1.5eq), 1- Methylimidazole. (1.6ul, 0.02mmol, 0.02eq) and toluene (3.8ml).Reactant mixture flows back 4.3 hours at 130 DEG C, tlc thin layer color Spectrum monitoring finishes to raw material 2,7- dibromo carbazole reaction.Saturated sodium bisulfite solution 5ml is quenched, and filters, and ethyl acetate is fully washed Wash insoluble matter, separate the organic faciess in mother solution, anhydrous sodium sulfate drying, filter, vacuum distillation removes solvent, and gained crude product is led to Cross silica gel column chromatogram separating purification, eluent: petroleum ether/dichloromethane=10:1-1:1, obtain white solid 332.9mg, yield 83%.
1h nmr(500mhz,cdcl3): δ 7.35-7.37 (m, 1h), 7.42 (dd, j=8.0,1.5hz, 2h), 7.57 (d, J=8.0hz, 1h), 7.89-7.99 (m, 5h), 8.74 (d, j=4.0hz, 1h)；13c nmr(125mhz,cdcl3):δ 114.38,119.00,120.20,121.29,122.05,122.54,124.52,138.91,140.38,149.96,150.73.
The preparation of the bromo- 9- of embodiment 27:3,6- bis- (2- pyridine radicals) carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add 3,6- dibromo carbazole (650.0mg, 2.00mmol, 1.0eq), Cu-lyt. (2.0mg, 0.02mmol, 0.01eq), tert-butyl alcohol lithium (240.2mg, 3.00mmol, 1.5eq), substitute nitrogen three times, be subsequently adding 2- bromopyridine (286.1ul, 3.00mmol, 1.5eq), 1- Methylimidazole. (3.2ul, 0.04mmol, 0.02eq) and toluene (7.6ml).Reactant mixture flows back 9.0 hours at 130 DEG C, tlc thin layer color Spectrum monitoring finishes to raw material 3,6- dibromo carbazole reaction.Saturated sodium bisulfite solution 5ml is quenched, and filters, and ethyl acetate is fully washed Wash insoluble matter, separate the organic faciess in mother solution, anhydrous sodium sulfate drying, filter, vacuum distillation removes solvent, and gained crude product is led to Cross silica gel column chromatogram separating purification, eluent: petrol ether/ethyl acetate=20:1-5:1, obtain white solid 738.0mg, yield 92%.
1h nmr(500mhz,cdcl3): δ 7.35 (dd, j=7.0,5.0hz, 1h), 7.53 (dd, j=8.5,1.5hz, 2h), 7.57 (d, j=8.0hz, 1h), 7.70 (d, j=9.0hz, 2h), 7.95 (td, j=7.5,1.5hz, 1h), 8.17 (d, j =1.5hz, 2h), 8.72 (d, j=3.5hz, 1h).13c nmr(125mhz,cdcl3): δ 112.88,114.05,118.89, 121.81,123.14,124.89,129.62,138.74,138.51,149.82,151.05.
The preparation of embodiment 28:3,6- di-t-butyl -9- (2- pyridine radicals) carbazole
Sequentially add 3,6- di-t-butyl carbazole to reflux condensing tube and being dried in there-necked flask of magnetic rotor (89.1mg, 0.25mmol, 1.0eq), Cu-lyt. (0.5mg, 0.005mmol, 0.02eq), tert-butyl alcohol lithium (40.0mg, 0.50mmol, 2.0eq), substitute nitrogen three times, be subsequently adding 2- bromopyridine (47.7ul, 0.50mmol, 2.0eq), 1- methyl miaow Azoles (0.8ul, 0.01mmol, 0.04eq) and toluene (1.0ml).Reactant mixture flows back 29 hours at 130 DEG C, tlc thin layer Chromatogram monitoring finishes to raw material 3,6- di-t-butyl carbazole reaction.Saturated sodium bisulfite solution 2ml is quenched, and filters, ethyl acetate Fully washing insoluble matter, separates the organic faciess in mother solution, anhydrous sodium sulfate drying, filters, vacuum distillation removes solvent, by gained Crude product passes through silica gel column chromatogram separating purification, eluent: petroleum ether/dichloromethane=10:1-1:1, obtains white solid 85.4mg, Yield 96%.
1h nmr(500mhz,cdcl3): δ 1.46 (s, 18h), 7.21-7.23 (m, 1h), 7.49 (dd, j=8.5, 2.0hz, 2h), 7.62 (d, j=8.0hz, 1h), 7.79 (d, j=8.5hz, 2h), 7.87 (td, j=8.0,2.0hz, 1h), 8.11 (d, j=2.0hz, 2h), 8.68 (dd, j=5.0,1.5hz, 1h)；13c nmr(125mhz,cdcl3):δ31.92, 34.71,110.74,116.05,118.29,120.54,123.87,124.35,137.86,138.22,143.84,149.45, 152.24.
The preparation of embodiment 29:3,6,8- tri-tert -9- (2- pyridine radicals) carbazole
Sequentially add 3,6,8- tri-tert carbazole to reflux condensing tube and being dried in there-necked flask of magnetic rotor (167.8mg, 0.50mmol, 1.0eq), Cu-lyt. (2.5mg, 0.025mmol, 0.05eq), tert-butyl alcohol lithium (80.1mg, 1.00mmol, 2.0eq), substitute nitrogen three times, be subsequently adding 2- bromopyridine (95.4ul, 1.00mmol, 2.0eq), 1- methyl miaow Azoles (4.0ul, 0.05mmol, 0.1eq) and toluene (2.0ml).Reactant mixture flows back 29 hours at 130 DEG C.Saturation sulfurous Acid sodium solution 2ml is quenched, and filters, and ethyl acetate is fully washed insoluble matter, separated the organic faciess in mother solution, and anhydrous sodium sulfate is done Dry, filter, vacuum distillation removes solvent, gained crude product is passed through silica gel column chromatogram separating purification, eluent: petroleum ether/dichloro Methane=10:1-1:1, obtains white solid 121.5mg, yield 59%, reclaims raw material 3,6,8- tri-tert carbazole simultaneously 42.5mg, the response rate 25%.
1h nmr(500mhz,cdcl3): δ 1.18 (s, 9h), δ 1.41 (s, 9h), δ 1.46 (s, 9h), 7.13 (d, j= 8.0hz, 1h), 7.24-7.27 (m, 2h), 7.34 (dd, j=8.5,2.0hz, 1h), 7.56 (d, j=2.0hz, 1h), 7.72 (td, j=8.0,2.0hz, 1h), 7.92 (d, j=2.0hz, 1h), 7.99 (d, j=1.5hz, 1h), 8.62 (dd, j=5.0, 1.5hz,1h).13c nmr(125mhz,cdcl3):δ31.57,31.86,31.88,34.61,34.78,35.37,112.13, 113.97,115.57,122.17,122.27,123.82,124.45,125.69,128.96,136.96,138.04,139.65, 143.87,144.39,144.63,149.23,158.22.
The preparation of embodiment 30:2- phenyl -9- (2- pyridine radicals) carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add 2- phenyl carbazole (60.8mg, 0.25mmol, 1.0eq), Cu-lyt. (0.5mg, 0.005mmol, 0.02eq), tert-butyl alcohol lithium (40.0mg, 0.50mmol, 2.0eq), substitute nitrogen three times, be subsequently adding 2- bromopyridine (35.8ul, 0.375mmol, 1.5eq), 1- Methylimidazole. (0.8ul, 0.01mmol, 0.04eq) and toluene (1.0ml).Reactant mixture flows back 3 hours at 130 DEG C, tlc thin layer chromatography Monitor and finish to the reaction of raw material 2- phenyl carbazole.Saturated sodium bisulfite solution 2ml is quenched, and filters, and ethyl acetate is fully washed not Molten thing, separates the organic faciess in mother solution, anhydrous sodium sulfate drying, filters, vacuum distillation removes solvent, gained crude product is passed through silicon Glue column chromatography separating purification, eluent: petroleum ether/dichloromethane=5:1-1:1, obtain white solid 79.0mg, yield 99%.
1h nmr(500mhz,cdcl3): δ 7.27-7.35 (m, 3h), 7.42-7.50 (m, 3h), 7.55 (dd, j=8.5, 1.5hz, 1h), 7.63-7.67 (m, 3h), 7.82 (d, j=8.5hz, 1h), 7.89 (td, j=8.0,2.0hz, 1h), 8.02 (d, j=1.0hz, 1h), 8.11 (d, j=8.0hz, 1h), 8.14 (d, j=8.0hz, 1h), 8.72 (dd, j=4.5,1.5hz, 1h)；13c nmr(125mhz,cdcl3):δ109.69,111.07,119.15,120.19,120.37,120.57,121.00, 121.28,123.47,124.02,126.19,127.03,127.55,128.66,138.48,139.68,140.04,140.09, 142.00,149.67,151.72.
The preparation of embodiment 31:2- benzothiazolyl carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add carbazole (41.8mg, 0.25mmol, 1.0eq), Cu-lyt. (0.3mg, 0.0025mmol, 0.01eq), tert-butyl alcohol lithium (30.0mg, 0.375mmol, 1.5eq), take out Change nitrogen three times, be subsequently adding 2- bromo benzothiazole (80.28mg, 0.375mmol, 1.5eq), 1- Methylimidazole. (0.41ul, 0.005mmol, 0.02eq) and toluene (2ml).Reactant mixture flows back 26 hours at 130 DEG C, tlc thin layer chromatography monitor to Raw material carbazole reaction finishes.Saturated sodium bisulfite solution is quenched, and filters, and ethyl acetate is fully washed insoluble matter, separated in mother solution Organic faciess, anhydrous sodium sulfate drying, filter, vacuum distillation removes solvent and excessive 2- bromo benzothiazole, by gained crude product By silica gel column chromatogram separating purification, eluent: petroleum ether/dichloromethane=10:1, obtain white solid 58.5mg, yield 78%.
1h nmr(500mhz,cdcl3): δ 7.38-7.42 (m, 3h), 7.52-7.57 (m, 3h), 7.89 (d, j=8.0hz, 1h), 8.07 (d, j=8.5hz, 1h), 8.09 (d, j=8.0hz, 2h), 8.49 (d, j=8.5hz, 2h)；13c nmr (500mhz,cdcl3): δ 113.25,120.11,121.13,122.27,122.72,124.57,125.25,126.58, 127.02,132.07,139.25,150.27,157.77.
The preparation of embodiment 32:9- [2- (1- tolimidazole base)] carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add carbazole (83.6mg, 0.5mmol, 1.0eq), 1- methyl -2- bromine benzimidazole (158.3mg, 0.75mmol, 1.5eq), Cu-lyt. (0.25mg, 0.025mmol, 0.05eq), tert-butyl alcohol lithium (120.0mg, 1.50mmol, 3.0eq), substitutes nitrogen three times, is subsequently adding 1- Methylimidazole. (0.40ul, 0.05mmol, 0.10eq) and toluene (2.0ml).Reactant mixture flows back 24 hours at 130 DEG C, tlc thin layer color Spectrum monitoring raw material carbazole.Saturated sodium bisulfite solution 2ml is quenched, and filters, and ethyl acetate is fully washed insoluble matter, separated in mother solution Organic faciess, anhydrous sodium sulfate drying, filter, vacuum distillation removes solvent, gained crude product passed through silica gel column chromatography separately pure Change, eluent: petrol ether/ethyl acetate=10:1, obtain water white transparency solid 30.6mg, yield 21%.
1h nmr(500mhz,cdcl3):δ3.52(s,3h),7.30-7.34(m,4h),7.37-7.44(m,5h)7.87- 7.90 (m, 1h), 8.10 (d, j=8.0hz, 2h).13c nmr(125mhz,cdcl3):δ30.62,109.73,110.73, 120.17,120.45,121.37,122.86,123.34,124.03,126.64,135.17,140.41,141.59,144.57.
The preparation of embodiment 33:9- [2- (1- tolimidazole base)] carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add carbazole (83.6mg, 0.5mmol, 1.0eq), 1- methyl -2- bromine benzimidazole (158.3mg, 0.75mmol, 1.5eq), Cu-lyt. (0.5mg, 0.005mmol, 0.01eq), tert-butyl alcohol lithium (60.0mg, 0.75mmol, 1.5eq), substitutes nitrogen three times, is subsequently adding 1- Methylimidazole. (0.8ul, 0.01mmol, 0.02eq) and toluene (2.0ml).Reactant mixture flows back 3.4 days hours at 130 DEG C, tlc thin layer Chromatogram monitoring raw material carbazole.Saturated sodium bisulfite solution 2ml is quenched, and filters, and ethyl acetate is fully washed insoluble matter, separated mother solution In organic faciess, anhydrous sodium sulfate drying, filter, vacuum distillation removes solvent, gained crude product passed through silica gel column chromatography separately Purification, eluent: petrol ether/ethyl acetate=10:1, obtain water white transparency solid 30.6mg, yield 21%.
1h nmr(500mhz,cdcl3):δ3.52(s,3h),7.30-7.34(m,4h),7.37-7.44(m,5h)7.87- 7.90 (m, 1h), 8.10 (d, j=8.0hz, 2h).13c nmr(125mhz,cdcl3):δ30.62,109.73,110.73, 120.17,120.45,121.37,122.86,123.34,124.03,126.64,135.17,140.41,141.59,144.57.
The preparation of embodiment 34:9- (2- pyridine radicals) azophenlyene
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add azophenlyene (183.2mg, 1.00mmol, 1.0eq), Cu-lyt. (2.0mg, 0.02mmol, 0.02eq), tert-butyl alcohol lithium (160.1mg, 2.00mmol, 2.0eq), substitute nitrogen three times, be subsequently adding 2- bromopyridine (190.7ul, 2.00mmol, 2.0eq), 1- Methylimidazole. (3.2ul, 0.04mmol, 0.04eq) and toluene (3.8ml).Reactant mixture flows back 24 hours at 130 DEG C, tlc thin layer color Spectrum monitoring raw material azophenlyene.Saturated sodium bisulfite solution 1ml is quenched, and filters, and ethyl acetate is fully washed insoluble matter, separated mother solution In organic faciess, anhydrous sodium sulfate drying, filter, vacuum distillation removes solvent, gained crude product passed through silica gel column chromatography separately Purification, eluent: petroleum ether/dichloromethane=10:1, obtain white solid 104.1mg, yield 40%.
1h nmr(500mhz,cdcl3): 6.42 (dd, j=7.5,1.0hz, 2h), 6.70 (dd, j=7.0,2.0hz, 1h), 6.72 (dd, j=7.0,2.5hz, 1h), 6.75-6.80 (m, 4h), 7.28 (ddd, j=6.0,4.5,1.0hz, 1h), 7.36 (d, j=8.0hz, 1h), 7.84 (td, j=7.5,2.0hz, 1h), 8.68 (dd, j=5.0,1.5hz, 1h).13c nmr (125mhz,cdcl3):δ115.89,116.00,122.03,122.13,122.79,123.24,132.81,139.46, 145.67,150.35,153.87.
The preparation of embodiment 35:9- (2- pyridine radicals) carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add carbazole (10.03g, 60.0mmol, 1.0eq), Cu-lyt. (60.0mg, 0.6mmol, 0.01eq), tert-butyl alcohol lithium (7.21g, 90.0mmol, 1.5eq), substitute nitrogen Gas three times, is subsequently adding 2- bromopyridine (8.58ml, 90.0mmol, 1.5eq), 1- Methylimidazole. (95.1ul, 1.2mmol, 0.02eq) with toluene (240ml).Reactant mixture is stirred at reflux 9.0 hours at 130 DEG C, and tlc thin layer chromatography is monitored to raw material Carbazole reaction finishes.Saturated sodium bisulfite solution 100ml is quenched, and filters, and ethyl acetate is fully washed insoluble matter, separated in mother solution Organic faciess, aqueous phase adopt 100ml ethyl acetate extract 3 times, merge organic faciess, 50ml wash, anhydrous sodium sulfate drying, mistake Filter, decompression rotary evaporation removes solvent, and vacuum distillation removes excessive 2- bromopyridine.Add 100ml dichloromethane and 4g silica gel It is stirred at reflux at 40 DEG C 3 hours, filters, dichloromethane fully washs, mother solution vacuum distillation is removed solvent and excessive 2- Bromopyridine.Gained crude product is isolated and purified by recrystallization, solvent ethyl acetate and petroleum ether, obtain white solid 8.61g, mother solution Silica gel column chromatography separates, eluent: petroleum ether/dichloromethane=2:1-1:3, obtains white solid 5.48g, amounts to 14.09g, always Yield is 95%.
1h nmr(500mhz,cdcl3): δ 7.27 (ddd, j=8.5,5.0,1.0hz, 1h), 7.29-7.32 (m, 2h), 7.43 (td, j=8.5,1.5hz, 2h), 7.61 (d, j=8.0hz, 1h), 7.83 (d, j=8.0hz, 2h), 7.88 (td, j= 8.0,2.0hz, 1h), 8.11 (d, j=7.5hz, 2h), 8.71 (dd, j=5.0,1.0hz, 1h). the bromo- 9- of embodiment 36:2- The preparation of (2- pyridine radicals) carbazole
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add 2- bromine carbazole (14.77g, 60.0mmol, 1.0eq), Cu-lyt. (60.0mg, 0.6mmol, 0.01eq), tert-butyl alcohol lithium (7.21g, 90.0mmol, 1.5eq), substitute nitrogen three times, be subsequently adding 2- bromopyridine (8.58ml, 90.0mmol, 1.5eq), 1- Methylimidazole. (95.1ul, 1.2mmol, 0.02eq) and toluene (240ml).Reactant mixture is stirred at reflux 5.0 hours at 130 DEG C, and tlc is thin Layer chromatography is monitored and is finished to raw material 2- bromine carbazole reaction.Saturated sodium bisulfite solution 100ml is quenched, and filters, and ethyl acetate is abundant Washing insoluble matter, separates the organic faciess in mother solution, and aqueous phase adopts 100ml ethyl acetate to extract 3 times, merges organic faciess, 50ml water Wash, anhydrous sodium sulfate drying, filter, decompression rotary evaporation removes solvent.Add 100ml dichloromethane and 4g silica gel at 40 DEG C It is stirred at reflux 3 hours, filters, dichloromethane fully washs, mother solution vacuum distillation is removed solvent and excessive 2- bromopyridine.Will Gained crude product is isolated and purified by recrystallization, solvent: dichloromethane and petroleum ether, obtains white solid 16.77g, yield 87%.
1h nmr(500mhz,cdcl3): δ 7.31-7.34 (m, 2h), 7.42 (dd, j=8.0,1.5hz, 1h), 7.44- 7.47 (m, 1h), 7.61 (d, j=8.5hz, 1h), 7.77 (d, j=8.0hz, 1h), 7.93-7.96 (m, 2h), 8.01 (d, j= 1.5hz, 1h), 8.08 (d, j=7.5hz, 1h), 8.73 (d, j=5.0,1.5hz, 1h).
The preparation of embodiment 37:2,6- bis- carbazole yl pyridines
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add carbazole (735.7mg, 4.4mmol, 2.2eq), Cu-lyt. (4.0mg, 0.04mmol, 0.02eq), tert-butyl alcohol lithium (480.3mg, 6.0mmol, 3.0eq), substitute nitrogen Gas three times, is subsequently adding 2,6- dibromo pyridine (473.8mg, 2.00mmol, 1.0eq), 1- Methylimidazole. (6.4ul, 0.08mmol, 0.04eq) and toluene (8.0ml).Reactant mixture flows back 3.0 hours at 130 DEG C, and tlc thin layer chromatography is monitored Finish to the reaction of raw material 2,6- dibromo pyridine.Saturated sodium bisulfite solution (2.0ml) is quenched, and filters, and ethyl acetate is fully washed Insoluble matter, separates the organic faciess in mother solution, anhydrous sodium sulfate drying, filters, vacuum distillation removes solvent, and gained crude product is passed through Silica gel column chromatogram separating purification, eluent: petroleum ether/dichloromethane=1:1, obtain white solid 751.3mg, yield 92%.
mp.243.1-245.3℃.1h nmr(500mhz,cdcl3):δ7.31-7.34(m,4h),7.39-7.42(m, 4h), 7.60 (d, j=8.0hz, 2h), 8.01 (d, j=8.0hz, 4h), 8.08 (t, j=8.0hz, 1h), 8.12 (d, j= 8.0hz,4h).13c nmr(126mhz,cdcl3):δ111.93,114.90,120.12,121.23, 124.54,126.32, 139.48,140.30,151.53. the preparation of embodiment 38:2,6- bis- (9- carbazyl) pyridine
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add 2,6- dibromo pyridine (14.21g, 60.00mmol, 1.0eq), carbazole (22.07g, 132.00mmol, 2.2eq), Cu-lyt. (120.0mg, 1.20mmol, 0.02eq), tert-butyl alcohol lithium (14.41g, 180.00mmol, 3.0eq), substitutes nitrogen three times, is subsequently adding 1- Methylimidazole. (190.2ul, 2.40mmol, 0.04eq) and toluene (240.0ml).Reactant mixture is stirred at reflux 4.0 hours at 130 DEG C, Tlc thin layer chromatography is monitored and is finished to the reaction of raw material 2,6- dibromo pyridine.Filtered by short silicagel column, chloroform fully washs insoluble Thing, separates mother solution vacuum distillation and removes solvent.Gained crude product is isolated and purified by recrystallization, add methanol (100.0ml) and Toluene (34ml), is stirred at reflux 2.0h, stirring at normal temperature 24.0h at 75 DEG C, filters, clean filter cake with petroleum ether, obtain white solid Body 23.15g, total recovery is 94%.
1h nmr(500mhz,dmso-d6): δ 7.33-7.36 (m, 4h), 7.43-7.47 (m, 4h), 7.87 (d, j= 8.0hz, 2h), 7.93 (d, j=8.0hz, 4h), 7.27 (d, j=7.5hz, 4h), 8.41 (d, j=8.0hz, 1h).
The preparation of embodiment 39:2,6- bis- carbazole yl pyridines
To with reflux condensing tube and magnetic rotor be dried in there-necked flask sequentially add carbazole (1337mg, 8.0mmol, 4.0eq), Cu-lyt. (4.0mg, 0.04mmol, 0.02eq), tert-butyl alcohol lithium (480.3mg, 6.0mmol, 3.0eq), substitute nitrogen Gas three times, is subsequently adding 2,6- dibromo pyridine (473.8mg, 2.00mmol, 1.0eq), 1- Methylimidazole. (6.4ul, 0.08mmol, 0.04eq) and toluene (8.0ml).Reactant mixture flows back 3.0 hours at 130 DEG C, and tlc thin layer chromatography is monitored Finish to the reaction of raw material 2,6- dibromo pyridine.Saturated sodium bisulfite solution (2.0ml) is quenched, and filters, and ethyl acetate is fully washed Insoluble matter, separates the organic faciess in mother solution, anhydrous sodium sulfate drying, filters, vacuum distillation removes solvent, and gained crude product is passed through Silica gel column chromatogram separating purification, eluent: petroleum ether/dichloromethane=1:1, obtain white solid 735mg, yield 90%.
1h nmr(500mhz,dmso-d6): δ 7.33-7.36 (m, 4h), 7.43-7.47 (m, 4h), 7.87 (d, j=8.0 Hz, 2h), 7.93 (d, j=8.0hz, 4h), 7.27 (d, j=7.5hz, 4h), 8.41 (d, j=8.0hz, 1h)..

Claims (10)

1. a kind of preparation method of n- heteroaryl carbazole compound is it is characterised in that methods described is carried out as follows:
With carbazole compound and hetaryl halogenides as raw material, cu (i) salt is catalyst, and 1- Methylimidazole. is part, in alkali 1.2 hours～5.0 are reacted in organic solvent in nitrogen protective condition at 110～130 DEG C in the presence of property material tert-butyl alcohol lithium My god, after question response terminates, reactant mixture is isolated and purified, obtain formula (i), formula (ii) or the n- heteroaryl shown in formula (iii) Carbazole compound；For compound, described carbazole compound and the hetaryl halogenides shown in formula (i) or formula (iii) The amount of material ratio be 1:1.1～3；For the compound shown in formula (ii), described carbazole compound and heteroaryl halogen The ratio of the amount of the material of compound is 2.2～4:1；Described hetaryl halogenides are hetaryl bromides or heteroaryl iodide,
In formula (i): x, y each stand alone as n or ch；In formula (iii): z is o, s or nr；
In formula (i), formula (ii) and formula (iii), r1～r19Each stand alone as h or, h is by deuterium, halogen, alkyl or adjacent two Substituent group forms benzo ring substituents with the heteroaryl being connected and replaces.
2. the method for claim 1 is it is characterised in that described carbazole compound is carbazole, 2- bromine carbazole, 3- bromine click Azoles, 2,7- dibromo carbazole, 3,6- dibromo carbazole, 3- phenyl carbazole, 3,6- di-t-butyl bromine carbazole or 1,3,6- tri-tert bromine Carbazole.
3. as claimed in claim 1 method it is characterised in that described hetaryl halogenides are 2- bromopyridine and its derivant, 2,6- Dibromo pyridine and its derivant, 2- bromoquinoline and its derivant, 2- bromo-isoquinoline and its derivant, 2- bromo-pyrazine and its derivative Thing, 2,5- bis- bromo-pyrazines and its derivant, 2- Bromopyrimidine and its derivant, the bromo- 1,3,5-triazines of 2- and its derivant, 2- is bromo- 1,2,5- triazine and its derivant, 2- bromo thiazole and its derivant, 2- bromo benzothiazole and its derivant, 2- bromine benzimidazole and Its derivant, 2- iodine pyridine and its derivant, 2,6- diiodopyridines and its derivant, 2- iodine quinoline and its derivant, 2- iodine is different Quinoline and its derivates, 2- iodine pyrazine and its derivant, 2,5- diiodo- pyrazines and its derivant, 2- iodine pyrimidine and its derivant, The iodo- 1,3,5-triazines of 2- and its derivant, iodo- 1,2, the 5- triazines of 2- and its derivant, 2- iodine thiazole and its derivant, 2- iodobenzene And thiazole and its derivant, or 2- iodobenzene imidazole and its derivants and their bromoiodide.
4. method as claimed in claim 1 is it is characterised in that described catalyst cu (i) salt is Hydro-Giene (Water Science)., Cu-lyt. or bromine Change cuprous.
5. method as claimed in claim 1 is it is characterised in that the amount of the material of described catalyst cu (i) salt and carbazole compound Ratio be 0.01～0.1:1.
6. method as claimed in claim 1 it is characterised in that described ligand 1-Methylimidazole. with cu (i) salt catalyst material The ratio of amount is 2.0～5.0:1.
7. method as claimed in claim 1 is it is characterised in that described tert-butyl alcohol lithium with the ratio of the amount of carbazole compound material is 1.2～3.0:1.
8. method as claimed in claim 1 it is characterised in that described organic solvent be toluene, dimethylbenzene, benzene or two of which appoint The mixture of meaning ratio.
9. method as claimed in claim 1 is it is characterised in that the addition of described organic solvent is with the material of carbazole compound Amount be calculated as 1～100ml/mmol.
10. method as claimed in claim 1 is it is characterised in that described reactant liquor Separation ＆ Purification method is: after reaction terminates, to Add saturated sodium bisulfite solution to be quenched in reactant liquor, filter and fully wash insoluble matter with ethyl acetate, take organic faciess With anhydrous sodium sulfate drying, filter to take filtrate, gained filtrate decompression is distilled off after solvent, with silica gel column chromatography or recrystallization Separate, obtain formula (i), formula (ii) or the n- heteroaryl carbazole compound shown in formula (iii).
CN201610769719.0A 2016-08-30 2016-08-30 A kind of preparation method of N- heteroaryl carbazole compound Active CN106366069B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201610769719.0A CN106366069B (en) 2016-08-30 2016-08-30 A kind of preparation method of N- heteroaryl carbazole compound

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201610769719.0A CN106366069B (en) 2016-08-30 2016-08-30 A kind of preparation method of N- heteroaryl carbazole compound

Publications (2)

Publication Number Publication Date
CN106366069A true CN106366069A (en) 2017-02-01
CN106366069B CN106366069B (en) 2019-01-08

Family

ID=57902115

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201610769719.0A Active CN106366069B (en) 2016-08-30 2016-08-30 A kind of preparation method of N- heteroaryl carbazole compound

Country Status (1)

Country Link
CN (1) CN106366069B (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP4151699A1 (en) 2021-09-17 2023-03-22 Universal Display Corporation Organic electroluminescent materials and devices

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102503753A (en) * 2011-09-29 2012-06-20 中国科学院化学研究所 Method for synthesizing 2-amino five-membered heterocyclic derivative
CN104232076A (en) * 2013-06-10 2014-12-24 代表亚利桑那大学的亚利桑那校董会 Phosphorescent tetradentate metal complexes having modified emission spectra

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102503753A (en) * 2011-09-29 2012-06-20 中国科学院化学研究所 Method for synthesizing 2-amino five-membered heterocyclic derivative
CN104232076A (en) * 2013-06-10 2014-12-24 代表亚利桑那大学的亚利桑那校董会 Phosphorescent tetradentate metal complexes having modified emission spectra

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
DANIEL T. ZIEGLER,ET AL.: "A Versatile Approach to Ullmann C−N Couplings at Room Temperature: New Families of Nucleophiles and Electrophiles for Photoinduced, Copper-Catalyzed Processes", 《J. AM. CHEM. SOC.》 *
WOO-JIN YOO,ET AL.: "Visible Light-Mediated Ullmann-Type C−N Coupling Reactions of Carbazole Derivatives and Aryl Iodides", 《ORGANIC LETTERS》 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP4151699A1 (en) 2021-09-17 2023-03-22 Universal Display Corporation Organic electroluminescent materials and devices

Also Published As

Publication number Publication date
CN106366069B (en) 2019-01-08

Similar Documents

Publication Publication Date Title
US7250510B2 (en) Transition metal complexes of N-heterocyclic carbenes, method of preparation and use in transition metal catalyzed organic transformations
Sahnoun et al. Microwave-assisted Pd (OH) 2-catalyzed direct C− H arylation of free-(NH2) adenines with aryl halides
CN101307065B (en) N-heterocyclic dicarbene metal complex connected with ether chain, method for preparing same and use
CN103917522A (en) Process for producing n-(hetero)arylazoles
Hayasaka et al. Highly efficient olefin hydrosilylation catalyzed by iron complexes with iminobipyridine ligand
CN107880079B (en) Cyclic N-heterocyclic bis-carbene-palladium complex and preparation method and application thereof
CN103772297A (en) Chiral hexahydroxy n-heterocyclic carbine precursor compound as well as preparation method and application thereof
Guo et al. Synthesis of 3 or 3, 3′-substituted BINOL ligands and their application in the asymmetric addition of diethylzinc to aromatic aldehydes
CN102977017B (en) Method for catalytically preparing 6(5H)-phenanthridine ketone by copper component
CN110452267A (en) The phosphorylated qualone derivative and preparation method and application that a kind of 3- replaces
CN104370930A (en) Method for efficiently preparing di(hetero)arylbenzopyrone/cyclopentanone derivative through rhodium catalysis-based C-H/C-H oxidation coupling reaction
CN106366069B (en) A kind of preparation method of N- heteroaryl carbazole compound
JP5963140B2 (en) Asymmetric dehydration condensation agent
Wang et al. Iron/Copper-Cocatalyzed Ullmann N, O-Arylation Using FeCl3, CuO, and rac-1, 1′-Binaphthyl-2, 2′-diol
CN107619385A (en) A kind of method that palladium chtalyst aryl enamine intramolecular amination synthesizes 2 trifluoro methyl indoles
JP6530807B2 (en) Process for the preparation of indenoisoquinoline derivatives
CN107915687B (en) High-efficiency preparation method of polysubstituted phenazine derivative and oxide thereof
CN114044751B (en) Deuterated difluoromethylthio reagent, preparation method thereof and introduction of SCF (SCF) into drug molecules 2 Method for preparing D group
WO2020118597A1 (en) Process for making 1- [ (3r, 4s) -4-cyanotetrahydropyran-3-yl] -3- [ (2-fluoro-6-methoxy-4-pyridyl) amino] pyrazole-4-carboxamide
JPWO2016125845A1 (en) Cross coupling method and method for producing organic compound using the cross coupling method
CN106397377B (en) The method of fluorine on a kind of electron rich five-ring heterocycles acid and its derivative decarboxylation
CN110563649B (en) High-selectivity deuteration method of 2-methyl nitrogen heterocyclic compound
CN111217847B (en) Thiosilane ligand, preparation method thereof and application thereof in aryl boronization catalytic reaction
CN112898202A (en) Heterocyclyl cyclopropane compound and synthesis method thereof
CN110526850A (en) The preparation method of 2,5- diaryl -3- cyanopyrrole compound

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
GR01 Patent grant
GR01 Patent grant