CN106977483A - A kind of synthetic method of the flavonols of fluoroalkyl substitution, isoflavones alcohol and coumarin kind compound - Google Patents
A kind of synthetic method of the flavonols of fluoroalkyl substitution, isoflavones alcohol and coumarin kind compound Download PDFInfo
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- CN106977483A CN106977483A CN201710409154.XA CN201710409154A CN106977483A CN 106977483 A CN106977483 A CN 106977483A CN 201710409154 A CN201710409154 A CN 201710409154A CN 106977483 A CN106977483 A CN 106977483A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
- C07D311/34—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 3 only
- C07D311/36—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 3 only not hydrogenated in the hetero ring, e.g. isoflavones
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
- C07D311/08—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring
- C07D311/16—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring substituted in position 7
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
- C07D311/28—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only
- C07D311/30—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only not hydrogenated in the hetero ring, e.g. flavones
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/42—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms in positions 2 and 4
- C07D311/44—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms in positions 2 and 4 with one hydrogen atom in position 3
- C07D311/46—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms in positions 2 and 4 with one hydrogen atom in position 3 unsubstituted in the carbocyclic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/42—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms in positions 2 and 4
- C07D311/44—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms in positions 2 and 4 with one hydrogen atom in position 3
- C07D311/54—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms in positions 2 and 4 with one hydrogen atom in position 3 substituted in the carbocyclic ring
Abstract
The synthetic method of the flavonols, isoflavones alcohol and the cumarin alcohol compound that replace this application discloses fluoroalkyl under the conditions of a kind of simplicity of organic synthesis field, specifically, it is the method for the flavonols, isoflavones alcohol and cumarin alcohol that obtain fluoroalkyl substitution in high yield by simple flavonols, isoflavones alcohol and cumarin alcoholic compound and bromine DF ester.Flavonols, isoflavones alcohol and the cumarin alcohol and bromine DF ester compounds that this method is obtained using natural product extraction are raw material, in the presence of weak base cheap and easy to get, and higher yields obtain target product with selectivity.Gentle with reaction condition, wide application range of substrates is easy to operate, the advantages of reaction efficiency is high.The structure of gained has the bioactivity such as antitumor, anti-oxidant, and the product of gained is also simultaneously the highly important intermediate of a class, can be used for further chemical modification, has larger application prospect in biomedicine field.
Description
Technical field
The present invention relates to organic synthesis field, and in particular to a kind of flavonols, isoflavones alcohol and the perfume (or spice) of fluoroalkyl substitution
The synthetic method of beans chlorins compound.
Background technology
Flavonoids and coumarin kind compound and its derivative are the class natural products being widely present in plant, at present
It was found that the structure of this kind of compound is more than 6000 kinds, wherein more than 1/3rd are connected with hydroxyl structure.Research discovery, this kind of chemical combination
Thing has quite varied bioactivity, such as antiviral (cyanidenon, baicalein), antitumor (such as umbelliferone), anti-
Osteoporosis, anti-oxidant and anticoagulation etc. are acted on so that they receive much concern in field of medicaments.However, due to active universal
It is not very high, cause the number of the independent patent medicine of this kind of compound seldom, is existed as adjuvant drug.In order to find
New medicines structure, it is a kind of highly effective means to be chemically modified.Recently, fluorine is introduced among drug leads molecule former
One of the important channel of son as new drug development, but existing technology can use freon, this will be polluted to air,
And its operating process is cumbersome, efficiency is low.
Conventional method
Heterocycle is the skeleton structure for being connected with different substituents flavones, isoflavones, cumarin.
The content of the invention
The invention is intended to provide a kind of flavonols of fluoroalkyl substitution, isoflavones alcohol and the synthetic method of cumarin alcohol,
To solve asking for flavonols, isoflavones alcohol and cumarin alcohol that the synthesis fluoroalkyl that prior art can not efficiently, succinct replaces
Topic.
In order to solve the above-mentioned technical problem, the present invention provides following basic technology scheme：A kind of Huang of fluoroalkyl substitution
The synthetic method of keto-alcohol, isoflavones alcohol and coumarin kind compound, in atent solvent, in the presence of a base, by compound A with changing
Compound B is reacted, so as to form compound C；
In above formula, heterocycle is the skeleton structure of the flavones, isoflavones, cumarin that are connected with different substituents；
R is C1-20 alkyl, the C1-20 alkyl of halo, C2-20 alkenyls, the C2-20 alkenyls of halo, C2-20 alkynyls, halo
C2-20 alkynyls, one kind in substituted or unsubstituted phenyl.
Beneficial effects of the present invention are：
Beneficial effects of the present invention：(1) method of the invention is reacted at room temperature, green, environmental protection.Simultaneous reactions step
Short, raw material and reagent are simple and easy to get, and need not move through pre-activate processing, compared with the conventional method, more economy and terseness.
(2) raw material that this method is related to is simple, be easy to get, without catalyst, it is not necessary to use gas, the substrate scope of application
Extensively, easy to operate, reaction efficiency is high, is adapted to larger amount of production,
(3) flavonols, isoflavones alcohol and the cumarin alcohol and its derivative of fluoroalkyl substitution produced by the present invention are in life
Thing field of medicaments has more important application prospect.
The following is the optimization to basic technology scheme：
Prioritization scheme one, based on base case：The compound A, alkali, compound B mol ratio are compound A：1~8,
Alkali：0.1~8, compound B：1~8.
Prioritization scheme two, prioritization scheme one：Described reaction is carried out at 0 DEG C~60 DEG C.
Prioritization scheme three, based on prioritization scheme one or prioritization scheme two：Described alkali is selected from：Carbonate, carboxylate, phosphoric acid
One kind in salt, villiaumite.
Prioritization scheme four, based on prioritization scheme one or prioritization scheme two：Described atent solvent is selected from：Acetonitrile, N- methyl
Pyrrolidones, N, N- dimethylformamides, dimethyl sulfoxide (DMSO), 1,3- dimethyl -3,4,5,6- tetrahydrochysene -2- pyrimidones, Isosorbide-5-Nitrae-two
One or more combinations in the ring of oxygen six, DMA.
Table 1：Testing record sheet
The information of above-mentioned table 1 directly feedback optimized scheme one to prioritization scheme four preferred result.
Embodiment
Technical solution of the present invention is described further with reference to embodiment：
The invention provides the synthesis side of a kind of flavonols of fluoroalkyl substitution, isoflavones alcohol and coumarin kind compound
Method, in atent solvent, (such as 0 DEG C~60 DEG C under certain temperature；Preferably 10 DEG C~60 DEG C), in the presence of base, by chemical combination
Thing A (i.e. flavonols, isoflavones alcohol and coumarin kind compound) and compound B reaction a period of time (such as 1~48h hour) so that
Form compound C (flavonols, isoflavones alcohol and the coumarin kind compound and its derivative of fluoroalkyl substitution)；
It is highly preferred that compound A is the compound being selected from the group：
In various, R is C1-20 alkyl, the C1-20 alkyl of halo, C2-20 alkenyls, the C2-20 alkenyls of halo, C2-20 alkynes
One kind in base, the C2-20 alkynyls of halo, substituted or unsubstituted phenyl.
Formula A and compound B can be prepared by the method known to commercially available or those skilled in the art of the invention
Obtain, however the actual conditions of this method, such as reactant, solvent, the amount of compound used therefor, reaction temperature, reaction taken
Between etc. be not limited to following explanation.
Alkali in the present invention includes：One kind in carbonate, phosphate, acetate, villiaumite.
Described atent solvent includes the solvent being selected from the group：Acetonitrile, 1-METHYLPYRROLIDONE (NMP), N, N- dimethyl
Formamide, dimethyl sulfoxide (DMSO), 1,3- dimethyl -3,4,5,6- tetrahydrochysene -2- pyrimidones (DMPU), Isosorbide-5-Nitrae-dioxane, N, N- bis-
One or more combinations in methylacetamide.Preferably, using acetonitrile and DMF.
In described reaction system, compound A or compound B reaction density are 0.01~1mmol/mL；Preferably, it is
0.1~0.5mmol/mL.
Further modification can be carried out to the compound C that the present invention is prepared as needed all kinds of so as to prepare
Functional compound, such as fluorine-containing cumarin and flavonols, the cumarin of the difluoro substitution with antitumor activity.
Product made from preparation method of the present invention can be isolated and purified by a variety of methods, and methods described includes：Weight
Crystallization, thin-layer chromatography, column chromatography etc..Above purification process is the conventional method of this area, for example, when being recrystallized, can
Using polar solvent and the mixed solvent of non-polar solven, preferably ethyl acetate-light petrol, ethanol-petroleum ether etc. mixes molten
Agent.During using thin-layer chromatography and column chromatography, the solvent that solvent used can be single can also use mixed solvent, such as oil
Mixed solvent of ether or ethyl acetate-light petrol etc..
The features described above that the present invention is mentioned, or the feature that following embodiment is mentioned can be in any combination.This case specification
Disclosed all features can be used in combination with any combinations thing form, and each feature disclosed in specification can be carried by any
For the alternative characteristics substitution of identical, impartial or similar purpose.Therefore except there is a special instruction, disclosed feature be only it is impartial or
The general example of similar features.
With reference to specific implementation, the present invention is expanded on further.It should be understood that these embodiments be merely to illustrate the present invention and
It is not used in limitation the scope of the present invention.The experimental method of unreceipted actual conditions in the following example, generally according to normal condition,
Or according to the condition proposed by manufacturer.Unless otherwise indicated, otherwise percentage and number are calculated by weight.
Purified in following examples using the conventional post-processing approach in this area.
Embodiment 1
Into 25mL reaction tube, 107mg (0.4mmo l equivalents) compound A-1,170mg (2 equivalent) K is added3PO4, nitrogen
Gas adds 3mL acetonitriles (MeCN) after replacing three times, injects 142 μ L (0.80mmol) compound B, is stirred at room temperature 48 hours
Afterwards, compound C-1 is obtained, yield is 47%.1H NMR(400MHz,CDCl3) δ 8.32 (d, J=9.2Hz, 1H), 7.98 (s, 1H),
7.50 (d, J=9.0Hz, 2H), 7.20 (s, 1H), 7.50 (d, J=9.2,2.0Hz, 1H), 6.98 (d, J=9.0Hz, 2H),
6.66 (t, J=72.6Hz, 1H), 3.85 (s, 3H)19F NMR(376MHz,CDCl3) δ -82.0 (d, J=72.2Hz, 2F)
Embodiment 2
Into 25mL reaction tube, 107mg (0.4mmol, 1 equivalent) compound A-1,110mg (2 equivalent) K is added2CO3,
3mL acetonitriles (MeCN) are added after nitrogen displacement three times, 142 μ L (0.80mmol) compound B are injected, it is stirred at room temperature 48 small
Shi Hou, obtains compound C-1, and yield is 71%.1H NMR(400MHz,CDCl3) δ 8.32 (d, J=9.2Hz, 1H), 7.98 (s,
1H), 7.50 (d, J=9.0Hz, 2H), 7.20 (s, 1H), 7.50 (d, J=9.2,2.0Hz, 1H), 6.98 (d, J=9.0Hz,
2H), 6.66 (t, J=72.6Hz, 1H), 3.85 (s, 3H)19F NMR(376MHz,CDCl3) δ -82.0 (d, J=72.2Hz,
2F).
Embodiment 3
Into 25mL reaction tube, 107mg (0.4mmol, 1 equivalent) compound A-1,261mg (2 equivalent) K is added2CO3,
3mL acetonitriles (MeCN) are added after nitrogen displacement three times, 142 μ L (0.80mmol) compound B are injected, it is stirred at room temperature 48 small
Shi Hou, obtains compound C-1, and yield is 54%.1H NMR(400MHz,CDCl3) δ 8.32 (d, J=9.2Hz, 1H), 7.98 (s,
1H), 7.50 (d, J=9.0Hz, 2H), 7.20 (s, 1H), 7.50 (d, J=9.2,2.0Hz, 1H), 6.98 (d, J=9.0Hz,
2H), 6.66 (t, J=72.6Hz, 1H), 3.85 (s, 3H)19F NMR(376MHz,CDCl3) δ -82.0 (d, J=72.2Hz,
2F).
Embodiment 4
Into 25mL reaction tube, 70.4mg (0.4mmol, 1 equivalent) compound A-2,110mg (2 equivalent) K is added2CO3,
3mL acetonitriles (MeCN) are added after nitrogen displacement three times, 142 μ L (0.80mmol) compound B is injected, is stirred at room temperature 48 hours
Afterwards, compound C-2 is obtained, yield is 90%.1H NMR(400MHz,CDCl3) δ 7.60 (d, J=8.4Hz, 1H), 7.09 (s, 1H),
(s, the 3H) of 7.08 (d, J=8.4Hz, 1H), 6.60 (t, J=72.6Hz, 1H), 6.27 (s, 1H), 2.4419F NMR(376MHz,
CDCl3) δ -81.8 (d, J=72.2Hz, 2F) this compound is noval chemical compound.
Embodiment 5
Into 25mL reaction tube, 64.8mg (0.4mmol, 1 equivalent) compound A-3,110mg (2 equivalent) K is added2CO3,
3mL acetonitriles (MeCN) are added after nitrogen displacement three times, 142 μ L (0.80mmol) compound B is injected, is stirred at room temperature 48 hours
Afterwards, compound C-3 is obtained, yield is 83%.1H NMR(400MHz,CDCl3) δ 7.69 (d, J=9.0Hz, 1H), 7.49 (d, J=
9.0Hz, 1H), 7.10 (s, 1H), 7.06 (d, J=8.4Hz, 1H), 6.60 (t, J=72.8Hz, 1H), 6.40 (t, J=
8.4Hz,1H).19F NMR(282MHz,CDCl3) δ -81.8 (d, J=73.7Hz, 2F) this compound is noval chemical compound.
Embodiment 6
Into 25mL reaction tube, 108mg (0.4mmol, 1 equivalent) compound A-4,170mg (2 equivalent) K is added3PO4,
3mL acetonitriles (MeCN) are added after nitrogen displacement three times, 142 μ L (0.80mmol) compound B is injected, is stirred at room temperature 48 hours
Afterwards, compound C-4 is obtained, yield is 55%.1H NMR(400MHz,d6-acetone)δ13.11(s,1H),8.60(s,1H),
8.34 (s, 1H), 7.48 (d, J=8.4Hz, 2H), 7.27 (t, J=73.2Hz, 1H), 6.92 (d, J=8.4Hz, 2H), 6.83
(s,1H),6.59(s,1H).19F NMR(376MHz,d6- acetone) δ -84.9 (d, J=73.3Hz, 2F)
Embodiment 7
Into 25mL reaction tube, 101.6mg (0.4mmol, 1 equivalent) compound A-5,170mg (2 equivalent) is added
K2CO3, 3mL acetonitriles (MeCN) are added after nitrogen displacement three times, are injected 142 μ L (0.80mmol) compound B, are stirred at room temperature
After 48 hours, compound C-5-a is obtained, yield is 64%.1H NMR(400MHz,CDCl3) δ 12.79 (s, 1H), 7.90 (d, J=
7.6Hz, 2H), 7.56 (m, 3H), 6.75 (s, 1H), 6.74 (s, 1H), 6.63 (t, J=72.8Hz, 1H), 6.56 (s, 1H)19F
NMR(376MHz,CDCl3) δ -82.3 (d, J=72.2Hz, 2F) this compound is noval chemical compound.
Embodiment 8
Into 25mL reaction tube, 101.6mg (0.4mmol, 1 equivalent) compound A-5,522mg (4 equivalent) is added
Cs2CO3, 3mL acetonitriles (MeCN) are added after nitrogen displacement three times, are injected 142 μ L (0.80mmol) compound B, are stirred at room temperature
After 48 hours, compound C-5-b is obtained, yield is 50%.1H NMR(400MHz,CDCl3) δ 7.88 (d, J=7.2Hz, 2H),
7.60-7.50 (m, 3H), 7.23 (s, 1H), 6.97 (s, 1H), 6.75 (t, J=75.0Hz, 1H), 6.74 (s, 1H), 6.67 (t,
J=72.0Hz, 1H)19F NMR(376MHz,CDCl3) δ -82.8 (d, J=71.8Hz, 2F), -83.9 (d, J=74.8Hz,
2F) this compound of is noval chemical compound.
Embodiment 9
Into 25mL reaction tube, 95.2mg (0.4mmol, 1 equivalent) compound A-6,261mg (2 equivalent) is added
Cs2CO3, 3mL acetonitriles (MeCN) are added after nitrogen displacement three times, are injected 142 μ L (0.80mmol) compound B, are stirred at room temperature
After 48 hours, compound C-6 is obtained, yield is 63%.1H NMR(400MHz,CDCl3) δ 8.27 (dd, J=8.2Hz, 1.4Hz,
1H), 8.10-8.02 (m, 2H), 7.74 (dt, J=8.2Hz, 1.6Hz, 1H), 7.60-7.50 (m, 4H), 7.46 (t, J=
7.8Hz, 1H), 7.20 (t, J=77.0Hz, 1H)19F NMR(376MHz,CDCl3) δ -82.3 (d, J=77.4Hz, 2F) this
Compound is noval chemical compound.
Embodiment 10
Into 25mL reaction tube, 70.4mg (0.4mmol, 1 equivalent) compound A-7,110mg (2 equivalent) K is added2CO3,
3mL acetonitriles (MeCN) are added after nitrogen displacement three times, 142 μ L (0.80mmol) compound B is injected, is stirred at room temperature 48 hours
Afterwards, compound C-7 is obtained, yield is 60%.1H NMR(400MHz,CDCl3) δ 7.60 (s, 1H), 7.42 (d, J=8.4Hz, 1H),
(s, the 3H) of 7.28-7.24 (m, 2H), 6.79 (t, J=71.2Hz, 1H), 5.94 (s, 1H), 2.4419F NMR(376MHz,
CDCl3) δ -84.8 (d, J=72.2Hz, 2F) this compound is noval chemical compound.
Embodiment 11
Into 25mL reaction tube, 64.8mg (0.4mmol, 1 equivalent) compound A-7,110mg (2 equivalent) K is added2CO3,
3mL acetonitriles (MeCN) are added after nitrogen displacement three times, 142 μ L (0.80mmol) compound B is injected, is stirred at room temperature 48 hours
Afterwards, compound C-8 is obtained, yield is 65%.1H NMR(400MHz,CDCl3) δ 7.82 (dd, J=7.8Hz, 1.4Hz, 1H), 7.63
(t, J=7.6Hz, 1H), 7.37 (d, J=7.6Hz, 1H), 7.35 (t, J=7.6Hz, 1H), 6.80 (t, J=71.2Hz, 1H),
5.97(s,3H).19F NMR(376MHz,CDCl3) δ -84.9 (d, J=72.2Hz, 2F)
Embodiment 12
Into 25mL reaction tube, 107.2mg (0.4mmol, 1 equivalent) compound A-9,110mg (2 equivalent) is added
K2CO3, 3mL acetonitriles (MeCN) are added after nitrogen displacement three times, are injected 142 μ L (0.80mmol) compound B, are stirred at room temperature
After 48 hours, compound C-9 is obtained, yield is 63%.1H NMR(400MHz,CDCl3) δ 8.27 (d, J=7.8Hz, 1H), 7.75
(t, J=7.6Hz, 1H), 7.65 (d, J=7.8Hz, 1H), 7.63 (s, 1H), 7.58 (d, J=8.8Hz, 1H), 7.47 (t, J=
7.6Hz, 1H), 7.46 (t, J=8.0Hz, 1H), 7.22 (t, J=77.6Hz, 1H), 7.10 (d, J=8.0Hz, 1H), 3.89
(s,3H).19F NMR(376MHz,CDCl3) δ -83.5 (d, J=77.4Hz, 2F) this compound is noval chemical compound.
Embodiment 13
Into 25mL reaction tube, 71.6mg (0.4mmol, 1 equivalent) compound A-10,110mg (2 equivalent) is added
K2CO3, 3mL acetonitriles (MeCN) are added after nitrogen displacement three times, inject 142 μ L (0.80mmol) compound B, it is stirred at room temperature
After 48 hours, compound C-10 is obtained, yield is 51%.1H NMR(400MHz,d6-acetone)δ8.93(s,1H),7.89(d,J
=8.8Hz, 1H), 7.26 (s, 1H), 7.18 (s, 1H), 7.11 (t, J=74.4Hz, 1H), 6.36 (t, J=10.0Hz, 1H)
.19F NMR(376MHz,d6- acetone) δ -81.5 (d, J=75.4Hz, 2F) .. this compound is noval chemical compound.
The compound C-1 of the synthesis of 1~embodiment of embodiment 13, compound C-2, compound C-3, compound C-4, compound
C-5-a, compound C-5-b, compound C-6, compound C-7, compound C-8, compound C-9 are the similar of some current medicines
Structure, partly with clear and definite bioactivity, is important intermediate, has larger application prospect in biomedicine field.
All documents referred in the present invention are all incorporated as reference in this application, independent just as each document
It is incorporated as with reference to such.In addition, it is to be understood that after the above-mentioned instruction content of the present invention has been read, those skilled in the art can
To be made various changes or modifications to the present invention, these equivalent form of values equally fall within what the application appended claims were limited
Scope.
Claims (5)
1. the synthetic method of a kind of flavonols of fluoroalkyl substitution, isoflavones alcohol and coumarin kind compound, it is characterised in that
In atent solvent, in the presence of a base, compound A is reacted with compound B, so as to form compound C；
2. synthetic method as claimed in claim 1, it is characterised in that：The compound A, alkali, compound B mol ratio are change
Compound A：1~8, alkali：0.1~8, compound B：1~8.
3. synthetic method as claimed in claim 1, it is characterised in that：Described reaction is carried out at 0 DEG C~60 DEG C.
4. synthetic method as claimed in claim 2 or claim 3, it is characterised in that：Described alkali is selected from：Carbonate, carboxylate, phosphoric acid
One kind in salt, villiaumite.
5. synthetic method as claimed in claim 2 or claim 3, it is characterised in that：Described atent solvent is selected from：Acetonitrile, N- methyl
Pyrrolidones, DMF, dimethyl sulfoxide (DMSO), 1,3- dimethyl -3,4,5,6- tetrahydrochysene -2- pyrimidones, Isosorbide-5-Nitrae-two
One or more combinations in the ring of oxygen six, DMA.
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| CN201710409154.XA CN106977483A (en) | 2017-06-02 | 2017-06-02 | A kind of synthetic method of the flavonols of fluoroalkyl substitution, isoflavones alcohol and coumarin kind compound |
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| CN201710409154.XA CN106977483A (en) | 2017-06-02 | 2017-06-02 | A kind of synthetic method of the flavonols of fluoroalkyl substitution, isoflavones alcohol and coumarin kind compound |
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| CN113636996A (en) * | 2021-09-02 | 2021-11-12 | 重庆大学 | Method for synthesizing 4-difluoromethoxy-substituted coumarin compound |
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| CN104870435A (en) * | 2012-12-21 | 2015-08-26 | 辉瑞大药厂 | Aryl and heteroaryl fused lactams |
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| US20170015675A1 (en) * | 2015-07-16 | 2017-01-19 | AbbVie S.à.r.l. | Substituted tricyclics and method of use |
| US9642831B2 (en) * | 2014-10-31 | 2017-05-09 | Abbvie S.Á.R.L. | Substituted chromanes and method of use |
| CN107531703A (en) * | 2015-04-23 | 2018-01-02 | 加拉帕戈斯股份有限公司 | For treating the new dihydro pyrido isobioquin group and its pharmaceutical composition of diseases associated with inflammation |
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| CN104870435A (en) * | 2012-12-21 | 2015-08-26 | 辉瑞大药厂 | Aryl and heteroaryl fused lactams |
| CN105658653A (en) * | 2013-08-23 | 2016-06-08 | 因赛特公司 | Furo- and thieno-pyridine carboxamide compounds useful as PIM kinase inhibitors |
| US9642831B2 (en) * | 2014-10-31 | 2017-05-09 | Abbvie S.Á.R.L. | Substituted chromanes and method of use |
| CN107531703A (en) * | 2015-04-23 | 2018-01-02 | 加拉帕戈斯股份有限公司 | For treating the new dihydro pyrido isobioquin group and its pharmaceutical composition of diseases associated with inflammation |
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| CN113636996A (en) * | 2021-09-02 | 2021-11-12 | 重庆大学 | Method for synthesizing 4-difluoromethoxy-substituted coumarin compound |
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