CN110483509A - A method of synthesis azepine indoline derivative object - Google Patents
A method of synthesis azepine indoline derivative object Download PDFInfo
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- CN110483509A CN110483509A CN201910831394.8A CN201910831394A CN110483509A CN 110483509 A CN110483509 A CN 110483509A CN 201910831394 A CN201910831394 A CN 201910831394A CN 110483509 A CN110483509 A CN 110483509A
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- 238000000034 method Methods 0.000 title claims abstract description 21
- LHEZUELISXETSY-UHFFFAOYSA-N N1CCC2=CC=CC=C12.N1C=CC=CC=C1 Chemical class N1CCC2=CC=CC=C12.N1C=CC=CC=C1 LHEZUELISXETSY-UHFFFAOYSA-N 0.000 title claims abstract description 11
- 238000003786 synthesis reaction Methods 0.000 title abstract description 11
- 230000015572 biosynthetic process Effects 0.000 title abstract description 8
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims abstract description 27
- 239000003054 catalyst Substances 0.000 claims abstract description 15
- 229910052761 rare earth metal Inorganic materials 0.000 claims abstract description 14
- 239000002994 raw material Substances 0.000 claims abstract description 14
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims abstract description 13
- 150000002910 rare earth metals Chemical class 0.000 claims abstract description 11
- 241001597008 Nomeidae Species 0.000 claims abstract description 8
- 238000010499 C–H functionalization reaction Methods 0.000 claims abstract description 7
- 230000002194 synthesizing effect Effects 0.000 claims abstract 7
- 150000003927 aminopyridines Chemical class 0.000 claims abstract 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 30
- 238000006243 chemical reaction Methods 0.000 claims description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 6
- BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 238000007363 ring formation reaction Methods 0.000 claims description 2
- 229910052727 yttrium Inorganic materials 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 3
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims 1
- 239000005977 Ethylene Substances 0.000 claims 1
- 229910052706 scandium Inorganic materials 0.000 claims 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 abstract description 42
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 abstract description 20
- 238000006555 catalytic reaction Methods 0.000 abstract description 2
- 125000003342 alkenyl group Chemical group 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 28
- 238000002360 preparation method Methods 0.000 description 13
- 239000000047 product Substances 0.000 description 8
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- 238000000926 separation method Methods 0.000 description 7
- -1 azaindole quinoline compound Chemical class 0.000 description 6
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 3
- JUPBNDCNONFYGF-UHFFFAOYSA-N 1,3-dimethyl-2,3-dihydropyrrole Chemical class CC1CN(C)C=C1 JUPBNDCNONFYGF-UHFFFAOYSA-N 0.000 description 2
- CALHJMWQJPIWTP-UHFFFAOYSA-N CC(C1)C=CN1C(C=C1)=CC=C1Cl Chemical class CC(C1)C=CN1C(C=C1)=CC=C1Cl CALHJMWQJPIWTP-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- LVYGKXJVXDMTRE-UHFFFAOYSA-N 1,3,5-trimethyl-2,3-dihydropyrrole Chemical class CN1CC(C=C1C)C LVYGKXJVXDMTRE-UHFFFAOYSA-N 0.000 description 1
- IMRWILPUOVGIMU-UHFFFAOYSA-N 2-bromopyridine Chemical compound BrC1=CC=CC=N1 IMRWILPUOVGIMU-UHFFFAOYSA-N 0.000 description 1
- KGIGUEBEKRSTEW-UHFFFAOYSA-N 2-vinylpyridine Chemical compound C=CC1=CC=CC=N1 KGIGUEBEKRSTEW-UHFFFAOYSA-N 0.000 description 1
- XHWAKSJWNNYHSH-UHFFFAOYSA-N 3-methyl-1-phenyl-2,3-dihydropyrrole Chemical class C1=CC(C)CN1C1=CC=CC=C1 XHWAKSJWNNYHSH-UHFFFAOYSA-N 0.000 description 1
- YMNCHKQJNNTGJA-UHFFFAOYSA-N CC1CN(C=C1)CC2=CC=CC=C2 Chemical class CC1CN(C=C1)CC2=CC=CC=C2 YMNCHKQJNNTGJA-UHFFFAOYSA-N 0.000 description 1
- 238000006783 Fischer indole synthesis reaction Methods 0.000 description 1
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical group C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 1
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical class C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses a kind of methods for synthesizing azepine indoline derivative object, belong to technical field of organic synthesis.The present invention realizes the azaindole quinoline derivant synthesis of structure diversification by rare earth catalyst pyridine carbon-hydrogen bond activation function dough.Specifically under rare-earth catalysis system, the aminopyridine replaced using various alkenyls prepares azaindole quinoline derivant as raw material.The method of the present invention raw material sources are extensive or easily prepared, easy to operate, selective controllable, high income, mild condition, and universality is wide.
Description
Technical field
The present invention relates to technical field of organic synthesis, in particular to pyridine carbon-hydrogen bond activation and intramolecular cyclization reaction to
Realize the azaindole quinoline derivant synthetic method of structure diversification.
Background technique
Azaindole quinoline is a kind of important organic compound, be both natural products and drug important component and
With unique optical property.Therefore, development diversification, efficient azaindole quinoline new synthetic method are always organic synthesis
Important topic in.
Existing to prepare in azaindole quinoline technology, there are the derivative reactions of pyridine skeleton before depending on always to construct nitrogen
Miscellaneous Benzazole compounds skeleton.And classical Fischer indole synthesis and Knut Fridell-Krafft is reacted due to pyridine ring
Short of electricity sub-feature be difficult it is derivative on the synthesis of azaindole quinoline.Document (Org. Lett.2008, 10, 1071-
1074) it reports with suitable (N, N- diallyl amino) bromopyridine for raw material, at -78 DEG C, with super dry pentane-two
Ether (9:1) is solvent, and tert-butyl lithium is as highly basic, the method that azaindole quinoline compound is prepared.The reaction of the type
The disadvantages of that there are functional group compatibilities is poor, severe reaction conditions has certain limitation.Document (Org. Lett. 2015, 17, It 3806-3809) reports and a kind of synthesizes Azaindoles chemical combination using two aminating reaction of high price iodine (III) direct oxidation
The method of object, although this method does not need harsh temperature, but need to carry out halogenation in advance to pyridine, and reaction process disappears
Halogen, complex steps need a large amount of additives, and the poor and most reaction systems of Atom economy are only suitable for constructing product skeleton
More single pyrido cycle compound has certain limitation.
Summary of the invention
The amino that the object of the present invention is to provide a kind of raw material sources extensively, can replace easily to operate from various vinyl
Pyridine is that raw material is highly selective, synthesizes method in azaindole quinoline derivant in high yield.
Above-mentioned technical purpose of the invention has the technical scheme that
A method of synthesis azepine indoline derivative object includes the following steps: the presence in nitrogen protection and rare earth catalyst
Under, in the reaction system for including organic solvent, by heating, the amino replaced with the various vinyl of compound shown in formula (I)
Pyridine is raw material, is inserted into cyclization by carbon-hydrogen bond activation intramolecular, compound azaindole shown in formula (II) is prepared
Quinoline derivant, reaction equation are as follows:
Wherein, R1The independent group in hydrogen, methyl, halogen；R2、R4It is independently selected from hydrogen, the group in methyl；
R3The independent group in methyl, phenyl, benzyl；R5The independent group in hydrogen, methyl, phenyl.
In above-mentioned technical proposal, the rare earth catalyst is selected from Ln [N (SiMe3)2]3, wherein Ln it is independent selected from Sc,
Y, La-Lu or rare earth alkyl complexes.
In above-mentioned technical proposal, the organic solvent is one of toluene, n-hexane or tetrahydrofuran.
It in above-mentioned technical proposal, is calculated with molar ratio, the amount ratio of the formula (I) compound and rare earth catalyst is 1.0:
0.1。
In above-mentioned technical proposal, the temperature of the heating is 100-120 DEG C, the time 24-48 of the heating
h。
It further include dibenzylamine in the reaction system in above-mentioned technical proposal.
In conclusion under rare-earth catalysis system, catalytic pyridine carbon-hydrogen bond activation/function dough and intramolecular insertion cyclisation
Reaction is to realize the synthesis of the azaindole quinoline derivant of structure diversification, and this method Atom economy is high, and bonding is high-efficient,
Reaction condition is mild.Compared to previous methods, reaction condition and substrate universality have clear improvement, this is that other methods are difficult to reality
Existing.The present invention has the following advantages that and innovation:
(1) reaction universality is good, and yield is high, and for most of reaction yield 80% or more, Atom economy is high；
(2) this is rare earth catalyst pyridine carbon-hydrogen bond activation/function dough important supplement, is provided for building nitrogen-containing heterocycle compound
Important thinking；
(3) reaction condition is more mild and does not need a large amount of/cumbersome additives.
(4) this method is also successfully applied to the synthesis of 7-naphthyridine derivatives.
(5) rare earth silicon amido composition catalyst is simple, moderate, commercially available；
The present invention compared with prior art the utility model has the advantages that
Azaindole quinoline derivant quality height, high income are prepared using the method for the present invention；It is good to react universality, reaction of atomic
Economy is high, convenient post-treatment；The building pyrido cyclisation of rare earth metal complex catalytic pyridine carbon-hydrogen bond activation is realized for the first time
Object is closed, the building for azaindole quinoline and other heterocyclic compounds provides important reference.
Detailed description of the invention
Fig. 1 is the reaction equation of present invention synthesis azepine indoline derivative object.
Specific embodiment
Below by specific embodiment, the present invention is described in detail, but the purposes and mesh of this exemplary embodiments
Be only used to enumerate the present invention, any type of any restriction not is constituted to real protection scope of the invention, it is more non-to incite somebody to action this
The protection scope of invention is confined to this.
Embodiment 1
The preparation of 1,3- dimethyl -2,3- dihydro -1H- pyrroles [3,2-b] pyridine, structural formula are as follows:
Under nitrogen protection, raw material N- allyl-N- picoline -3- amine (0.5 mmol) is added into toluene (3 mL) and urges
Agent Y [N (SiMe3)2]3 (10 mol%) reacts 24 h preparation 1,3- dimethyl -2,3- dihydro -1H- pyrroles at 100 DEG C
[3,2-b] pyridine, product separation yield are 90%.
1H NMR (CDCl3, 500 MHz, ppm): δ 7.75 (d, J = 5.0 Hz, 1H), 6.85 (dd, J
= 5.1, 7.8 Hz, 1H), 6.55 (d, J = 7.9 Hz, 1H), 3.52 (t, J = 8.8 Hz, 1H), 3.26-
3.22 (m, 1H), 2.82 (t, J = 8.5 Hz, 1H), 2.67 (s, 3H), 1.32 (d, J = 7.0 Hz,
3H). 13C NMR (CDCl3, 125 MHz, ppm): δ 156.9, 146.5, 137.8, 121.8, 112.0, 62.1,
36.6, 35.6, 17.1.
Embodiment 2
The preparation of 1,3,5- trimethyl -2,3- dihydro -1H- pyrroles [3,2-b] pyridine, structural formula are as follows:
Under nitrogen protection, raw material N- allyl-N, 6- lutidines -3- amine (0.5 mmol) is added into toluene (3 mL)
With catalyst Y [N (SiMe3)2]3 (10 mol%) reacts 24 h preparation 1,3,5- trimethyl -2,3- dihydros-at 100 DEG C
1H- pyrroles [3,2-b] pyridine, product separation yield are 81%.
1H NMR (CDCl3, 500 MHz, ppm): δ 6.75 (d, J = 7.9 Hz, 1H), 6.54 (d, J =
7.9 Hz, 1H), 3.47 (t, J = 8.6 Hz, 1H), 3.26-3.21 (m, 1H), 2.84 (t, J = 8.3
Hz, 1H), 2.67 (s, 3H), 2.40 (s, 3H), 1.33 (d, J = 7.0 Hz, 3H). 13C NMR (CDCl3,
125 MHz, ppm): δ 156.6, 146.4, 144.4, 120.8, 113.3, 62.6, 36.9, 36.4, 23.4,
17.5.
Embodiment 3
The preparation of chloro- 1,3- dimethyl -2,3- dihydro -1H- pyrroles [3, the 2-b] pyridine of 5-, structural formula are as follows:
Under nitrogen protection, raw material N- allyl -6- chloro-n-methyl pyridine -3- amine (0.5 is added into toluene (3 mL)
Mmol), dibenzylamine (10 mol%) and catalyst Y [N (SiMe3)2]3 (10 mol%) reacts 24 h preparation 5- at 100 DEG C
Chloro- 1,3- dimethyl -2,3- dihydro -1H- pyrroles [3,2-b] pyridine, product separation yield are 86%.
1H NMR (CDCl3, 500 MHz, ppm): δ 6.91 (dd, J = 0.6, 8.2 Hz, 1H), 6.55
(d, J = 8.2 Hz, 1H), 3.57 (t, J = 8.9 Hz, 1H), 3.29-3.23 (m, 1H), 2.91 (dd, J
= 8.0, 8.7 Hz, 1H), 2.71 (s, 3H), 1.33 (d, J = 6.9 Hz, 3H). 13C NMR (CDCl3,
125 MHz, ppm):δ 157.4, 145.7, 138.7, 121.7, 114.8, 62.3, 36.6, 35.8, 17.4.
Embodiment 4
The preparation of 1- benzyl -3- methyl -2,3- dihydro -1H- pyrroles [3,2-b] pyridine, structural formula are as follows:
Under nitrogen protection, raw material N- allyl-N- benzyl pyridine -3- amine (0.5 mmol), two are added into toluene (3 mL)
Benzylamine (10 mol%) and catalyst Y [N (SiMe3)2]3 (10 mol%) reacts 24 h preparation 1- benzyl -3- first at 100 DEG C
Base -2,3- dihydro -1H- pyrroles [3,2-b] pyridine, product separation yield are 83%.
1H NMR (CDCl3, 500 MHz, ppm): δ 7.82 (d, J =4.7 Hz, 1H), 7.36-7.27 (m,
5H), 6.89 (dd, J = 5.2, 7.8 Hz, 1H), 6.62(d, J = 7.8 Hz, 1H), 4.31(d, J =
14.9 Hz, 1H), 4.16(d, J = 14.9 Hz, 1H), 3.60(t, J = 9.0 Hz, 1H), 3.36-3.31
(m, 1H), 2.95(t, J = 8.5 Hz, 1H), 1.38(d, J = 6.9 Hz, 3H). 13C NMR (CDCl3, 125
MHz, ppm): δ 156.9, 145.8, 138.0, 137.6, 128.7, 127.9, 127.5, 121.9, 112.0,
59.8, 53.1, 36.6, 17.6.
Embodiment 5
The preparation of 3- methyl-1-phenyl-2,3- dihydro-1H- pyrroles [3,2-b] pyridine, structural formula are as follows:
Under nitrogen protection, raw material N- allyl-N- phenylpyridine -3- amine (0.5 mmol), two are added into toluene (3 mL)
Benzylamine (10 mol%) and catalyst Y [N (SiMe3)2]3 (10 mol%), reacts 24 h at 100 DEG C, and product separation yield is
92%。
1H NMR (CDCl3, 500 MHz, ppm): δ 7.91 (d, J = 4.9 Hz, 1H), 7.36 (t, J =
7.6 Hz, 2H), 7.30 (d, J = 8.0 Hz, 1H), 7.19 (d, J = 7.9 Hz, 2H), 7.00 (t, J =
7.3 Hz, 1H), 6.93 (dd, J = 5.0, 8.0 Hz, 1H), 4.11 (t, J = 9.2 Hz, 1H), 3.59
(t, J = 9.0 Hz, 1H), 3.52-3.45 (m, 1H), 1.46 (d, J = 6.9 Hz, 3H),. 13C NMR
(CDCl3, 125 MHz, ppm): δ 157.9, 143.6, 140.6, 139.2, 129.4, 121.7, 121.6,
117.2, 113.4, 58.2, 36.1, 18.1.
Embodiment 6
The preparation of 3- methyl-1-(p-methylphenyl)-2,3- dihydro-1H- pyrroles [3,2-b] pyridine, structural formula are as follows:
Under nitrogen protection, raw material N- allyl-N- (p-methylphenyl) pyridine -3- amine (0.5 is added into toluene (3 mL)
Mmol), dibenzylamine (10 mol%) and catalyst Y [N (SiMe3)2]3 (10 mol%) reacts 24 h preparation 3- at 100 DEG C
Methyl-1-(p-methylphenyl)-2,3- dihydro-1H- pyrroles [3,2-b] pyridine, product separation yield are 61%.
1H NMR (CDCl3, 500 MHz, ppm): δ 7.88 (d, J = 4.8 Hz, 1H), 7.23 (d, J =
8.0 Hz, 1H), 7.17 (d, J = 8.3 Hz, 2H), 7.10 (d, J = 8.4 Hz, 2H), 6.93 (dd, J
= 5.1, 7.8 Hz, 1H), 4.09 (t, J = 9.0 Hz, 1H), 3.57 (t, J = 8.7 Hz, 1H), 3.52-
3.46 (m, 1H), 2.33 (s, 3H), 1.46 (d, J = 6.8 Hz, 3H),. 13C NMR (CDCl3, 125
MHz, ppm): δ 157.7, 141.2, 141.1, 138.6, 131.5, 130.0, 121.7, 117.7, 113.2,
58.5, 36.2, 20.8, 18.1.
Embodiment 7
The preparation of 1- (4- chlorphenyl) -3- methyl -2,3- dihydro -1H- pyrroles [3,2-b] pyridine, structural formula are as follows:
Under nitrogen protection, raw material N- allyl-N- (4- chlorphenyl) pyridine -3- amine (0.5 is added into toluene (3 mL)
Mmol), dibenzylamine (10 mol%) and catalyst Y [N (SiMe3)2]3 (10 mol%) reacts 24 h preparation 1- at 100 DEG C
(4- chlorphenyl) -3- methyl -2,3- dihydro -1H- pyrroles [3,2-b] pyridine, product separation yield are 87%.
1H NMR (CDCl3, 500 MHz, ppm): δ 7.91 (d, J = 4.9 Hz, 1H), 7.30-7.27
(m, 2H), 7.24 (d, J = 8.1 Hz, 1H), 7.12-7.08 (m, 2H), 6.94 (dd, J = 5.0, 8.0
Hz, 1H), 4.08 (t, J = 8.8 Hz, 1H), 3.57-3.46 (m, 2H), 1.45 (d, J = 6.7 Hz,
3H). 13C NMR (CDCl3, 125 MHz, ppm): δ 157.8, 142.1, 140.3, 139.5, 129.4,
126.4, 121.7, 118.4, 113.6, 58.3, 36.1, 18.1.
It should be noted that the organic solvent toluene in embodiment 1-6 could alternatively be n-hexane or tetrahydrofuran, reaction temperature
It can be changed according to the actual situation in 100-120 DEG C and 24-48 h of section respectively with the reaction time.
Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention., rather than its limitations；To the greatest extent
Pipe present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that: its according to
Right scientific research modifies the technical solutions described in the foregoing embodiments, or to some or all of the technical features into
Row equivalent replacement；And these are modified or replaceed, various embodiments of the present invention technology that it does not separate the essence of the corresponding technical solution
The range of scheme.
Claims (6)
1. a kind of method for synthesizing azepine indoline derivative object, which comprises the steps of: in nitrogen protection and rare earth
In the presence of catalyst, in the reaction system for including organic solvent, by heating, with the various ethylene of compound shown in formula (I)
The aminopyridine that base replaces is raw material, is inserted into cyclization by carbon-hydrogen bond activation intramolecular, formula (II) shownization is prepared
Close object azaindole quinoline derivant, reaction equation are as follows:
Wherein, R1The independent group in hydrogen, methyl, halogen；R2、R4It is independently selected from hydrogen, the group in methyl；R3
The independent group in methyl, phenyl, benzyl；R5The independent group in hydrogen, methyl, phenyl.
2. a kind of method for synthesizing azepine indoline derivative object according to claim 1, it is characterised in that: the rare earth
Catalyst is selected from Ln [N (SiMe3)2]3, wherein Ln is independent is selected from Sc, Y, La-Lu or rare earth alkyl complexes.
3. a kind of method for synthesizing azepine indoline derivative object according to claim 1, it is characterised in that: described is organic
Solvent is one of toluene, n-hexane or tetrahydrofuran.
4. a kind of method for synthesizing azepine indoline derivative object according to claim 1, it is characterised in that: with molar ratio computing
It calculates, the amount ratio of the formula (I) compound and rare earth catalyst is 1.0:0.1.
5. a kind of method for synthesizing azepine indoline derivative object according to claim 1, it is characterised in that: the heating
Temperature be 100-120 DEG C, 24-48 h of time of the heating.
6. a kind of method for synthesizing azepine indoline derivative object according to claim 1, it is characterised in that: the reaction
It further include dibenzylamine in system.
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| CN113773244A (en) * | 2021-04-06 | 2021-12-10 | 复旦大学 | Method for removing ketone fragment in nitrogen heterocyclic compound substituent |
| CN113773244B (en) * | 2021-04-06 | 2024-03-22 | 复旦大学 | Method for removing ketone fragment in nitrogen heterocyclic compound substituent |
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