CN108976198A - A kind of synthetic method of 3- (4- pyridine) Benzazole compounds - Google Patents
A kind of synthetic method of 3- (4- pyridine) Benzazole compounds Download PDFInfo
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- CN108976198A CN108976198A CN201811073559.1A CN201811073559A CN108976198A CN 108976198 A CN108976198 A CN 108976198A CN 201811073559 A CN201811073559 A CN 201811073559A CN 108976198 A CN108976198 A CN 108976198A
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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Abstract
The invention discloses a kind of synthetic methods of 3- (4- pyridine) Benzazole compounds, belong to technical field of organic synthesis.A kind of technical solution of the present invention main points are as follows: synthetic method of 3- (4- pyridine) Benzazole compounds; specific steps are as follows: acetic acid oxime ester compound and 3- formyl indole or derivatives thereof are dissolved in solvent; then catalyst and nitrogenous organic base is added, is reacted in seal pipe in 100-130 DEG C and 3- (4- pyridine) Benzazole compounds is made.Synthesis process of the present invention is simple and efficient, by the way that 3- (4- pyridine) Benzazole compounds are directly made without one pot of transition metal-catalyzed one step of tandem reaction, it avoids due to the use of plurality of reagents in multistep reaction and to the wasting of resources and environmental pollution caused by purification process of each step reaction intermediate etc., raw material is easily prepared, reaction condition is mild, wide application range of substrates.
Description
Technical field
The invention belongs to technical field of organic synthesis, and in particular to a kind of synthesis side of 3- (4- pyridine) Benzazole compounds
Method.
Background technique
Studies have shown that 3- (4- pyridine) indole derivatives have significant bioactivity, it is that potential inosine monophosphate is de-
Hydrogen enzyme, Rho- kinase inhibitor and anti-malignant cell proliferation therapeutic agent have important application in biology and medicine and other fields
Value.And the synthetic method of presently relevant 3- reported in the literature (4- pyridine) Benzazole compounds mainly passes through palladium chtalyst
Suzuki coupling reaction, metal catalytic alkynes cycloaddition reaction andMade from reaction.These literature methods have make
The disadvantages of with expensive catalyst, substrate narrow application range, severe reaction conditions and low yield, which greatly limits
The application of such synthetic method in actual production.Therefore, the importance in view of 3- (4- pyridine) Benzazole compounds and existing
The deficiency of synthetic method, the synthetic method for developing simple and direct, efficient such compound are very necessary.
Summary of the invention
The technical problem to be solved by the present invention is to provide a kind of starting materials simply easily to prepare, wide application range of substrates, area
Field selectivity is high, reaction condition is mild and the synthetic method of 3- (4- pyridine) Benzazole compounds easy to operate.
The present invention adopts the following technical scheme that solve above-mentioned technical problem, a kind of 3- (4- pyridine) Benzazole compounds
Synthetic method, it is characterised in that specific steps are as follows: be dissolved in acetic acid oxime ester compound 1 and 3- formyl indole class compound 2
In solvent, catalyst and nitrogenous organic base is then added, is reacted in seal pipe in 100-130 DEG C and target product 3- (4- is made
Pyridine) Benzazole compounds 3, the reaction equation in the synthetic method are as follows:
Wherein R1For phenyl, substituted-phenyl, 2- naphthalene or thienyl, the substituted-phenyl be 3,4- methylenedioxyphenyl,
3,4- dichloride base phenyl or mono-substituted benzenes base, the substituent group on mono-substituted benzenes base phenyl ring are methyl, methoxyl group, nitro, chlorine
Or bromine, R2For hydrogen, methyl, methoxyl group, methoxybenzyl, fluorine, chlorine, carbomethoxy or nitro, R3For hydrogen or methyl, solvent is toluene, chlorine
Benzene, acetonitrile, Isosorbide-5-Nitrae-dioxane, tetrahydrofuran (THF) or n,N-Dimethylformamide (DMF), catalyst are elemental iodine, N- iodine
For succimide or ammonium iodide, nitrogenous organic base is triethylamine, diethylamine, pyridine, Isosorbide-5-Nitrae-diazabicylo [2.2.2] octane
(DABCO), 11 carbon -7- alkene (DBU) of 1,8- diazabicylo or quinoline.
Further preferably, the acetic acid oxime ester compound 1,3- formyl indole or derivatives thereof 2, catalyst with it is nitrogenous
The molar ratio of organic base is 2:1:1:1, and the charge ratio of acetic acid oxime ester compound 1 and solvent is 1mmol:2mL.
The synthetic method of 3- (4- pyridine) Benzazole compounds of the present invention, it is characterised in that specific steps are as follows: will
Acetic acid oxime ester compound 1l and 3- formyl indole 2a is dissolved in solvent Isosorbide-5-Nitrae-dioxane, and catalyst iodine simple substance is then added
With nitrogenous organic base pyridine, is reacted in seal pipe in 110 DEG C and target product quinoline -4- Carbox amide 3l is made, it should
Reaction equation in synthetic method are as follows:
Further preferably, acetic acid oxime ester compound 1l, 3- formyl indole 2a, catalyst iodine simple substance have with nitrogenous
The molar ratio of machine alkali pyridine is 2:1:1:1, acetic acid oxime ester compound 1l and solvent Isosorbide-5-Nitrae-dioxane charge ratio
For 1mmol:2mL.
Further preferably, 3- (4- pyridine) Benzazole compounds 3 are one of following compounds:
Compared with the prior art, the present invention has the following advantages: 1, synthesis process be without transition metal-catalyzed one pot series connection
Reaction, process is simple, efficient, while avoiding due to the use of plurality of reagents in multistep reaction and to each step reaction intermediate
Purification process etc. caused by the wasting of resources and environmental pollution；2, raw material is easily prepared；3, reaction condition is mild, easy to operate；
4, substrate is applied widely.Therefore, the present invention provides a kind of economical real for the synthesis of 3- (4- pyridine) Benzazole compounds
With and environmentally protective new method.
Specific embodiment
Above content of the invention is described in further details by the following examples, but this should not be interpreted as to this
The range for inventing above-mentioned theme is only limitted to embodiment below, and all technologies realized based on above content of the present invention belong to this hair
Bright range.
Embodiment 1
Compound 1a (1.0mmol, 191mg), compound 2a (0.5mmol, 72.6mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and Isosorbide-5-Nitrae-dioxane (2mL), are subsequently placed in 110 DEG C of oil baths
In be stirred to react 12h.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, later organic phase mass concentration
For 10% Na2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel post separation
(petrol ether/ethyl acetate=10/1, v/v) obtains white solid product 3a (153.3mg, 82%).The characterization number of the compound
According to as follows:1H NMR(400MHz,DMSO-d6): δ (ppm) 11.79 (s, 1H), 8.29 (d, J=2.8Hz, 1H), 8.21 (d, J=
8.0Hz, 4H), 8.15 (s, 2H), 8.13-8.08 (m, 1H), 7.58-7.50 (m, 1H), 7.36 (d, J=8.0Hz, 4H),
7.26–7.22(m,2H),2.39(s,6H)；13C NMR(100MHz,DMSO-d6)δ(ppm)156.1,145.4,138.4,
137.2,136.5,129.3,126.7,126.5,124.8,121.9,120.5,119.3,115.0,113.4,112.3,20.9；
HRMS(ESI):m/z[M+Na]+calcd for C27H22N2Na:397.1675；found:397.1676.
Embodiment 2
Compound 1a (1.0mmol, 191mg), compound 2a (0.5mmol, 72.6mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), triethylamine (0.5mmol, 50.5mg) and chlorobenzene (2mL), are subsequently placed in 130 DEG C of oil baths and stir
React 12h.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, organic phase mass concentration is 10% later
Na2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel post separation (petroleum
Ether/ethyl acetate=10/1, v/v) obtain white solid product 3a (121.6mg, 65%).
Embodiment 3
Compound 1a (1.0mmol, 191mg), compound 2a (0.5mmol, 72.6mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), triethylamine (0.5mmol, 50.5mg) and toluene (2mL), are subsequently placed in 130 DEG C of oil baths and stir
React 12h.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, organic phase mass concentration is 10% later
Na2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel post separation (petroleum
Ether/ethyl acetate=5/1, v/v) obtain white solid product 3a (112.2mg, 60%).
Embodiment 4
Compound 1a (1.0mmol, 191mg), compound 2a (0.5mmol, 72.6mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), triethylamine (0.5mmol, 50.5mg) and Isosorbide-5-Nitrae-dioxane (2mL), are subsequently placed in 130 DEG C of oil
12h is stirred to react in bath.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, organic phase quality is dense later
The Na that degree is 10%2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silicagel column point
White solid product 3a (142.1mg, 76%) is obtained from (petrol ether/ethyl acetate=5/1, v/v).
Embodiment 5
Compound 1a (1.0mmol, 191mg), compound 2a (0.5mmol, 72.6mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), triethylamine (0.5mmol, 50.5mg) and acetonitrile (2mL), are subsequently placed in 130 DEG C of oil baths and stir
React 12h.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, organic phase mass concentration is 10% later
Na2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel post separation (petroleum
Ether/ethyl acetate=5/1, v/v) obtain white solid product 3a (134.6mg, 72%).
Embodiment 6
Compound 1a (1.0mmol, 191mg), compound 2a (0.5mmol, 72.6mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), triethylamine (0.5mmol, 50.5mg) and tetrahydrofuran (2mL), are subsequently placed in 130 DEG C of oil baths
It is stirred to react 12h.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, organic phase is with mass concentration later
10% Na2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel post separation (stone
Oily ether/ethyl acetate=5/1, v/v) obtain white solid product 3a (129mg, 69%).
Embodiment 7
Compound 1a (1.0mmol, 191mg), compound 2a (0.5mmol, 72.6mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), triethylamine (0.5mmol, 50.5mg) and n,N-Dimethylformamide (2mL), are subsequently placed in 130
12h is stirred to react in DEG C oil bath.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, later organic phase matter
Measure the Na that concentration is 10%2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel
Post separation (petrol ether/ethyl acetate=5/1, v/v) obtains white solid product 3a (89.8mg, 48%).
Embodiment 8
Compound 1a (1.0mmol, 191mg), compound 2a (0.5mmol, 72.6mg), N- are added in 25mL seal pipe
N-iodosuccinimide (0.5mmol, 112.5mg), triethylamine (0.5mmol, 50.5mg) and Isosorbide-5-Nitrae-dioxane (2mL), so
It is placed in 130 DEG C of oil baths and is stirred to react 12h.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, later
The Na that organic phase mass concentration is 10%2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, rotation
It is dry, it crosses silica gel post separation (petrol ether/ethyl acetate=5/1, v/v) and obtains white solid product 3a (110.3mg, 59%).
Embodiment 9
Compound 1a (1.0mmol, 191mg), compound 2a (0.5mmol, 72.6mg), iodine are added in 25mL seal pipe
Change ammonium (0.5mmol, 72.5mg), triethylamine (0.5mmol, 50.5mg) and Isosorbide-5-Nitrae-dioxane (2mL), is subsequently placed in 130 DEG C
12h is stirred to react in oil bath.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, later organic phase quality
The Na that concentration is 10%2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silicagel column
Separation (petrol ether/ethyl acetate=5/1, v/v) obtains white solid product 3a (78.5mg, 42%).
Embodiment 10
Compound 1a (1.0mmol, 191mg), compound 2a (0.5mmol, 72.6mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), diethylamine (0.5mmol, 36.6mg) and Isosorbide-5-Nitrae-dioxane (2mL), are subsequently placed in 130 DEG C of oil
12h is stirred to react in bath.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, organic phase quality is dense later
The Na that degree is 10%2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silicagel column point
White solid product 3a (127.2mg, 68%) is obtained from (petrol ether/ethyl acetate=5/1, v/v).
Embodiment 11
Compound 1a (1.0mmol, 191mg), compound 2a (0.5mmol, 72.6mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), 1,4- diazabicylo [2.2.2] octane (0.5mmol, 56mg) and 1,4- dioxane
(2mL) is subsequently placed in 130 DEG C of oil baths and is stirred to react 12h.50mL water quenching reaction is added, be extracted with ethyl acetate (50mL ×
3), the Na that organic phase mass concentration is 10% later2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.
Filtering, be spin-dried for, cross silica gel post separation (petrol ether/ethyl acetate=5/1, v/v) obtain white solid product 3a (119.7mg,
64%).
Embodiment 12
Compound 1a (1.0mmol, 191mg), compound 2a (0.5mmol, 72.6mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), 11 carbon -7- alkene (0.5mmol, 76mg) of 1,8- diazabicylo and 1,4- dioxane
(2mL) is subsequently placed in 130 DEG C of oil baths and is stirred to react 12h.50mL water quenching reaction is added, be extracted with ethyl acetate (50mL ×
3), the Na that organic phase mass concentration is 10% later2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.
Filtering, be spin-dried for, cross silica gel post separation (petrol ether/ethyl acetate=5/1, v/v) obtain white solid product 3a (80.4mg,
43%).
Embodiment 13
Compound 1a (1.0mmol, 191mg), compound 2a (0.5mmol, 72.6mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), quinoline (0.5mmol, 64.6mg) and Isosorbide-5-Nitrae-dioxane (2mL), are subsequently placed in 130 DEG C of oil baths
In be stirred to react 12h.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, later organic phase mass concentration
For 10% Na2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel post separation
(petrol ether/ethyl acetate=5/1, v/v) obtains white solid product 3a (76.7mg, 41%).
Embodiment 14
Compound 1a (1.0mmol, 191mg), compound 2a (0.5mmol, 72.6mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and Isosorbide-5-Nitrae-dioxane (2mL), are subsequently placed in 130 DEG C of oil baths
In be stirred to react 12h.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, later organic phase mass concentration
For 10% Na2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel post separation
(petrol ether/ethyl acetate=5/1, v/v) obtains white solid product 3a (153.3mg, 82%).
Embodiment 15
Compound 1a (1.0mmol, 191mg), compound 2a (0.5mmol, 72.6mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and Isosorbide-5-Nitrae-dioxane (2mL), are subsequently placed in 100 DEG C of oil baths
In be stirred to react 12h.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, later organic phase mass concentration
For 10% Na2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel post separation
(petrol ether/ethyl acetate=5/1, v/v) obtains white solid product 3a (136.5mg, 73%).
Embodiment 16
Compound 1b (1.0mmol, 177mg), compound 2a (0.5mmol, 72.6mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and Isosorbide-5-Nitrae-dioxane (2mL), are subsequently placed in 110 DEG C of oil baths
In be stirred to react 12h.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, later organic phase mass concentration
For 10% Na2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel post separation
(petrol ether/ethyl acetate=10/1, v/v) obtains white solid product 3b (136.7mg, 79%).The characterization number of the compound
According to as follows:1H NMR(400MHz,DMSO-d6): δ (ppm) 11.81 (s, 1H), 8.32 (d, J=7.6Hz, 5H), 8.22 (s,
2H), 8.14 (d, J=4.4Hz, 1H), 7.64-7.53 (m, 5H), 7.52-7.45 (m, 2H), 7.29-7.21 (m, 2H)；13C
NMR(100MHz,DMSO-d6)δ(ppm)156.3,145.6,139.2,137.2,129.0,128.7,126.8,126.6,
124.8,121.9,120.6,119.4,115.7,113.3,112.3；HRMS(ESI):m/z[M+H]+calcd for
C25H19N2:347.1543；found:347.1545.
Embodiment 17
Compound 1c (1.0mmol, 207mg), compound 2a (0.5mmol, 72.6mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and Isosorbide-5-Nitrae-dioxane (2mL), are subsequently placed in 110 DEG C of oil baths
In be stirred to react 12h.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, later organic phase mass concentration
For 10% Na2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel post separation
(petrol ether/ethyl acetate=10/1, v/v) obtains white solid product 3c (180.6mg, 89%).The characterization number of the compound
According to as follows:1H NMR(400MHz,DMSO-d6): δ (ppm) 11.78 (s, 1H), 8.27 (d, J=7.6Hz, 5H), 8.16-8.02
(m, 3H), 7.56 (d, J=5.6Hz, 1H), 7.25 (d, J=3.6Hz, 2H), 7.11 (d, J=8.4Hz, 4H), 3.83 (s,
6H)；13C NMR(100MHz,DMSO-d6)δ(ppm)160.1,155.9,145.3,137.2,131.9,128.1,126.4,
124.9,121.9,120.5,119.4,114.2,114.1,113.6,112.4,55.2；HRMS(ESI):m/z[M+H]+calcd
for C27H23N2O2:407.1754；found:407.1757.
Embodiment 18
Compound 1d (1.0mmol, 221mg), compound 2a (0.5mmol, 72.6mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and Isosorbide-5-Nitrae-dioxane (2mL), are subsequently placed in 110 DEG C of oil baths
In be stirred to react 12h.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, later organic phase mass concentration
For 10% Na2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel post separation
(petrol ether/ethyl acetate=10/1, v/v) obtains white solid product 3d (188.8mg, 87%).The characterization number of the compound
According to as follows:1H NMR(400MHz,DMSO-d6):δ(ppm)11.76(s,1H),8.28(s,1H),8.10(s,1H),8.07(s,
2H), 7.87 (s, 3H), 8.84 (s, 1H), 7.53 (d, J=4.4Hz, 1H), 7.23 (d, J=2.8Hz, 2H), 7.08 (d, J=
7.6Hz,2H),6.12(s,4H)；13C NMR(100MHz,DMSO-d6)δ(ppm)155.5,148.1,147.9,145.4,
137.2,133.7,126.5,124.8,121.9,120.9,120.5,119.5,114.7,113.4,112.3,108.4,
107.0,101.3；HRMS(ESI):m/z[M+H]+calcd for C27H19N2O4:435.1339；found:435.1338.
Embodiment 19
Compound 1e (1.0mmol, 222mg), compound 2a (0.5mmol, 72.6mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and Isosorbide-5-Nitrae-dioxane (2mL), are subsequently placed in 110 DEG C of oil baths
In be stirred to react 12h.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, later organic phase mass concentration
For 10% Na2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel post separation
(petrol ether/ethyl acetate=10/1, v/v) obtains white solid product 3e (154.7mg, 71%).The characterization number of the compound
According to as follows:1H NMR(400MHz,DMSO-d6): δ (ppm) 11.84 (s, 1H), 9.03 (s, 2H), 8.70 (d, J=7.6Hz,
2H), 8.36 (d, J=2.8Hz, 1H), 8.34 (s, 2H), 8.31 (d, J=2.0Hz, 1H), 8.29 (d, J=2.0Hz, 1H),
8.12 (d, J=7.2Hz, 1H), 7.82 (t, J=8.0Hz, 2H), 7.55-7.50 (m, 1H), 7.28-7.18 (m, 2H)；13C
NMR(100MHz,DMSO-d6)δ(ppm)154.0,148.4,146.4,140.4,137.2,133.1,130.3,127.4,
124.6,123.7,122.0,121.2,120.6,119.5,116.9,112.7,112.3；HRMS(ESI):m/z[M+Na]+
calcd for C25H16N4NaO4:459.1064；found:459.1069.
Embodiment 20
Compound 1f (1.0mmol, 211mg), compound 2a (0.5mmol, 72.6mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and Isosorbide-5-Nitrae-dioxane (2mL), are subsequently placed in 110 DEG C of oil baths
In be stirred to react 12h.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, later organic phase mass concentration
For 10% Na2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel post separation
(petrol ether/ethyl acetate=10/1, v/v) obtains white solid product 3f (126.5mg, 61%).The characterization number of the compound
According to as follows:1H NMR(400MHz,DMSO-d6):δ(ppm)11.89(s,1H),8.43(s,2H),8.40(s,3H),8.31(s,
2H), 8.23-8.18 (m, 1H), 7.68 (d, J=8.4Hz, 4H), 7.64-7.59 (m, 1H), 7.35-7.28 (m, 2H)；13C
NMR(100MHz,DMSO-d6)δ(ppm)155.0,145.9,137.8,137.2,133.9,128.7,128.6,126.9,
124.7,122.0,120.6,119.4,115.8,113.0,112.3；HRMS(ESI):m/z[M+H]+calcd for
C25H17Cl2N2:415.0763；found:415.0764.
Embodiment 21
Compound 1g (1.0mmol, 256mg), compound 2a (0.5mmol, 72.6mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and Isosorbide-5-Nitrae-dioxane (2mL), are subsequently placed in 110 DEG C of oil baths
In be stirred to react 12h.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, later organic phase mass concentration
For 10% Na2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel post separation
(petrol ether/ethyl acetate=10/1, v/v) obtains white solid product 3g (161.3mg, 64%).The characterization number of the compound
According to as follows:1H NMR(400MHz,DMSO-d6): δ (ppm) 11.81 (s, 1H), 8.31 (d, J=2.8Hz, 1H), 8.28-8.20
(m, 6H), 8.14-8.09 (m, 1H), 7.73 (d, J=8.4Hz, 4H), 7.56-7.51 (m, 1H), 7.28-7.19 (m, 2H)；13C
NMR(100MHz,DMSO-d6)δ(ppm)155.1,145.9,138.2,137.2,131.6,128.9,126.9,124.7,
122.7,122.0,120.6,119.4,115.8,113.0,112.4；HRMS(ESI):m/z[M+H]+calcd for
C25H17Br2N2:502.9753；found:502.9758.
Embodiment 22
Compound 1h (1.0mmol, 246mg), compound 2a (0.5mmol, 72.6mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and Isosorbide-5-Nitrae-dioxane (2mL), are subsequently placed in 110 DEG C of oil baths
In be stirred to react 12h.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, later organic phase mass concentration
For 10% Na2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel post separation
(petrol ether/ethyl acetate=10/1, v/v) obtains white solid product 3h (167mg, 69%).The characterize data of the compound
It is as follows:1H NMR(400MHz,DMSO-d6): δ (ppm) 11.81 (s, 1H), 8.43 (s, 2H), 8.30 (d, J=4.4Hz, 1H),
8.24-8.15 (m, 4H), 8.08 (d, J=7.2Hz, 1H), 7.74-7.67 (m, 2H), 7.52 (d, J=7.6Hz, 1H), 7.28-
7.17(m,2H)；13C NMR(100MHz,DMSO-d6)δ(ppm)153.6,146.1,139.3,137.2,131.7,131.6,
130.7,128.4,127.2,126.8,124.6,121.9,120.5,119.5,116.3,112.8,112.3；HRMS(ESI):
m/z[M+H]+calcd for C25H15Cl4N2:482.9984；found:482.9988.
Embodiment 23
Compound 1i (1.0mmol, 227mg), compound 2a (0.5mmol, 72.6mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and Isosorbide-5-Nitrae-dioxane (2mL), are subsequently placed in 110 DEG C of oil baths
In be stirred to react 12h.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, later organic phase mass concentration
For 10% Na2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel post separation
(petrol ether/ethyl acetate=10/1, v/v) obtains white solid product 3i (131.5mg, 59%).The characterization number of the compound
According to as follows:1H NMR(400MHz,DMSO-d6): δ (ppm) 11.86 (s, 1H), 8.93 (s, 2H), 8.57 (d, J=8.4Hz,
2H), 8.43 (s, 2H), 8.40 (d, J=2.4Hz, 1H), 8.26-8.21 (m, 1H), 8.17 (d, J=7.2Hz, 2H), 8.12
(d, J=8.8Hz, 2H), 8.01 (d, J=6.8Hz, 2H), 7.63-7.55 (m, 5H), 7.32-7.25 (m, 2H)；13C NMR
(100MHz,DMSO-d6)δ(ppm)156.3,145.7,137.3,136.7,133.3,133.2,128.7,128.2,127.6,
126.7,126.6,126.4,126.1,124.8,122.0,120.6,119.5,116.2,113.4,112.4；HRMS(ESI):
m/z[M+H]+calcd for C33H23N2:447.1856；found:447.1859.
Embodiment 24
Compound 1j (1.0mmol, 183mg), compound 2a (0.5mmol, 72.6mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and Isosorbide-5-Nitrae-dioxane (2mL), are subsequently placed in 110 DEG C of oil baths
In be stirred to react 12h.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, later organic phase mass concentration
For 10% Na2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel post separation
(petrol ether/ethyl acetate=10/1, v/v) obtains white solid product 3j (116.3mg, 65%).The characterization number of the compound
According to as follows:1H NMR(400MHz,DMSO-d6):δ(ppm)11.82(s,1H),8.28(s,1H),8.19–8.05(m,3H),
7.98 (s, 2H), 7.66 (d, J=4.4Hz, 2H), 7.55 (d, J=5.2Hz, 1H), 7.29-7.10 (m, 4H)；13C NMR
(100MHz,DMSO-d6)δ(ppm)151.8,145.4,144.6,137.2,128.4,128.3,126.8,125.4,124.7,
122.0,120.6,119.5,113.5,112.7,112.4；HRMS(ESI):m/z[M+Na]+calcd for C21H14N2NaS2:
381.0491；found:381.0492.
Embodiment 25
Compound 1k (1.0mmol, 183mg), compound 2a (0.5mmol, 72.6mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and Isosorbide-5-Nitrae-dioxane (2mL), are subsequently placed in 110 DEG C of oil baths
In be stirred to react 12h.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, later organic phase mass concentration
For 10% Na2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel post separation
(petrol ether/ethyl acetate=10/1, v/v) obtains white solid product 3k (128.9mg, 72%).The characterization number of the compound
According to as follows:1H NMR(400MHz,DMSO-d6): δ (ppm) 11.78 (s, 1H), 8.38 (d, J=2.0Hz, 2H), 8.25 (d, J=
2.8Hz, 1H), 8.16-8.12 (m, 1H), 8.08 (s, 2H), 7.97 (d, J=5.2Hz, 2H), 7.70-7.66 (m, 2H),
7.57–7.52(m,1H),7.29–7.19(m,2H)；13C NMR(100MHz,DMSO-d6)δ(ppm)152.8,145.3,
142.4,137.2,126.8,126.7,126.5,124.8,124.2,121.9,120.5,119.6,115.1,113.1,
112.3；HRMS(ESI):m/z[M-H]-calcd for C21H13N2S2:357.0526；found:357.0521.
Embodiment 26
Compound 1l (1.0mmol, 203mg), compound 2a (0.5mmol, 72.6mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and Isosorbide-5-Nitrae-dioxane (2mL), are subsequently placed in 110 DEG C of oil baths
In be stirred to react 12h.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, later organic phase mass concentration
For 10% Na2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel post separation
(petrol ether/ethyl acetate=10/1, v/v) obtains white solid product 3l (147.3mg, 74%).The characterization number of the compound
According to as follows:1H NMR(400MHz,DMSO-d6): δ (ppm) 11.52 (s, 1H), 8.47 (d, J=7.2Hz, 2H), 7.53 (d, J=
8.0Hz, 1H), 7.47 (d, J=2.4Hz, 1H), 7.40 (t, J=7.2Hz, 2H), 7.34-7.28 (m, 2H), 7.23 (d, J=
7.2Hz, 2H), 7.20-7.13 (m, 2H), 7.00 (t, J=7.2Hz, 1H), 2.86-2.73 (m, 4H), 2.73-2.66 (m,
4H)；13C NMR(100MHz,DMSO-d6)δ(ppm)149.1,141.3,137.8,136.1,134.9,130.5,128.6,
127.6,126.8,126.5,125.0,124.7,121.4,119.4,118.9,111.9,110.1,27.5,25.6；HRMS
(ESI):m/z[M+H]+calcd for C29H23N2:399.1856；found:399.1855.
Embodiment 27
Compound 1b (1.0mmol, 177mg), compound 2b (0.5mmol, 79.6mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and Isosorbide-5-Nitrae-dioxane (2mL), are subsequently placed in 110 DEG C of oil baths
In be stirred to react 12h.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, later organic phase mass concentration
For 10% Na2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel post separation
(petrol ether/ethyl acetate=10/1, v/v) obtains white solid product 3m (138.6mg, 77%).The characterization number of the compound
According to as follows:1H NMR(400MHz,DMSO-d6): δ (ppm) 11.66 (s, 1H), 8.30 (d, J=7.6Hz, 4H), 8.22 (d, J=
2.8Hz, 1H), 8.17 (s, 2H), 7.85 (s, 1H), 7.57 (t, J=7.6Hz, 4H), 7.49 (t, J=7.2Hz, 2H), 7.41
(d, J=8.4Hz, 1H), 7.06 (d, J=8.0Hz, 1H), 2.48 (s, 3H)；13C NMR(100MHz,DMSO-d6)δ(ppm)
156.2,145.8,139.3,135.5,129.2,129.0,128.8,126.8,126.6,125.0,123.6,118.8,
115.7,112.8,112.1,21.6；HRMS(ESI):m/z[M+Na]+calcd for C26H20N2Na:383.1519；found:
383.1518。
Embodiment 28
Compound 1b (1.0mmol, 177mg), compound 2c (0.5mmol, 79.6mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and Isosorbide-5-Nitrae-dioxane (2mL), are subsequently placed in 110 DEG C of oil baths
In be stirred to react 12h.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, later organic phase mass concentration
For 10% Na2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel post separation
(petrol ether/ethyl acetate=10/1, v/v) obtains white solid product 3n (113.4mg, 63%).The characterization number of the compound
According to as follows:1H NMR(400MHz,DMSO-d6): δ (ppm) 11.64 (s, 1H), 8.31 (d, J=7.2Hz, 4H), 8.23 (d, J=
2.4Hz, 1H), 8.19 (s, 2H), 7.99 (d, J=8.4Hz, 1H), 7.57 (t, J=7.6Hz, 4H), 7.48 (t, J=7.2Hz,
2H), 7.32 (s, 1H), 7.06 (d, J=8.4Hz, 1H), 2.45 (s, 3H)；13C NMR(100MHz,DMSO-d6)δ(ppm)
156.2,145.7,139.3,137.7,131.1,129.0,128.7,126.8,126.0,122.7,122.3,119.1,
115.5,113.1,112.1,21.3；HRMS(ESI):m/z[M+Na]+calcd for C26H20N2Na:383.1519；found:
383.1520。
Embodiment 29
Compound 1b (1.0mmol, 177mg), compound 2d (0.5mmol, 79.6mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and Isosorbide-5-Nitrae-dioxane (2mL), are subsequently placed in 110 DEG C of oil baths
In be stirred to react 12h.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, later organic phase mass concentration
For 10% Na2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel post separation
(petrol ether/ethyl acetate=10/1, v/v) obtains white solid product 3o (118.8mg, 66%).The characterization number of the compound
According to as follows:1H NMR(400MHz,DMSO-d6):δ(ppm)11.75(s,1H),8.34–8.29(m,5H),8.21(s,2H),
7.95 (d, J=8.0Hz, 1H), 7.57 (t, J=7.4Hz, 4H), 7.49 (t, J=7.2Hz, 2H), 7.14 (t, J=7.6Hz,
1H), 7.04 (d, J=6.8Hz, 1H), 2.55 (s, 3H)；13C NMR(100MHz,DMSO-d6)δ(ppm)156.2,145.7,
139.2,136.7,129.0,128.7,126.8,126.4,124.5,122.5,121.6,120.8,116.9,115.6,
113.7,16.9；HRMS(ESI):m/z[M+H]+calcd for C26H21N2:361.1699；found:361.1696.
Embodiment 30
Compound 1b (1.0mmol, 177mg), compound 2e (0.5mmol, 87.6mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and Isosorbide-5-Nitrae-dioxane (2mL), are subsequently placed in 110 DEG C of oil baths
In be stirred to react 12h.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, later organic phase mass concentration
For 10% Na2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel post separation
(petrol ether/ethyl acetate=10/1, v/v) obtains white solid product 3p (101.5mg, 54%).The characterization number of the compound
According to as follows:1H NMR(400MHz,DMSO-d6): δ (ppm) 11.65 (s, 1H), 8.33-8.28 (m, 4H), 8.22 (d, J=
2.4Hz, 1H), 8.16 (s, 2H), 7.56 (t, J=7.4Hz, 4H), 7.51-7.46 (m, 3H), 7.43 (d, J=8.8Hz, 1H),
6.94–6.87(m,1H),3.85(s,3H)；13C NMR(100MHz,DMSO-d6)δ(ppm)156.2,154.4,145.7,
139.2,132.3,129.0,128.8,127.1,126.8,125.2,115.5,113.1,113.0,111.6,101.4,55.4；
HRMS(ESI):m/z[M+Na]+calcd for C26H20N2NaO:399.1468；found:399.1468.
Embodiment 31
In 25mL seal pipe be added compound 1b (1.0mmol, 177mg), compound 2f (0.5mmol, 125.6mg),
Elemental iodine (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and Isosorbide-5-Nitrae-dioxane (2mL), are subsequently placed in 110 DEG C of oil
12h is stirred to react in bath.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, organic phase quality is dense later
The Na that degree is 10%2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silicagel column point
White solid product 3q (126.5mg, 56%) is obtained from (petrol ether/ethyl acetate=10/1, v/v).The characterization of the compound
Data are as follows:1H NMR(400MHz,DMSO-d6): δ (ppm) 11.69 (s, 1H), 8.29 (d, J=7.2Hz, 4H), 8.24 (d, J
=2.8Hz, 1H), 8.12 (s, 2H), 7.61-7.55 (m, 5H), 7.52-7.44 (m, 5H), 7.37-7.28 (m, 3H), 7.04-
6.97(m,1H),5.26(s,2H)；13C NMR(100MHz,DMSO-d6)δ(ppm)156.3,153.4,145.7,139.3,
137.9,132.4,129.0,128.7,128.4,127.6,127.3,127.2,126.8,125.1,115.5,113.1(3),
113.0(9),112.7,102.9,69.8；HRMS(ESI):m/z[M+H]+calcd for C32H25N2O:453.1961；
found:453.1962。
Embodiment 32
Compound 1b (1.0mmol, 177mg), compound 2g (0.5mmol, 81.6mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and Isosorbide-5-Nitrae-dioxane (2mL), are subsequently placed in 110 DEG C of oil baths
In be stirred to react 12h.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, later organic phase mass concentration
For 10% Na2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel post separation
(petrol ether/ethyl acetate=10/1, v/v) obtains white solid product 3r (125.6mg, 69%).The characterization number of the compound
According to as follows:1H NMR(400MHz,DMSO-d6): δ (ppm) 11.91 (s, 1H), 8.37 (s, 1H), 8.33 (d, J=6.8Hz,
4H), 8.16 (s, 2H), 7.83 (d, J=10.0Hz, 1H), 7.56 (d, J=6.4Hz, 5H), 7.49 (d, J=6.4Hz, 2H),
7.10 (t, J=8.8Hz, 1H)；13C NMR(100MHz,DMSO-d6)δ(ppm)159.0,156.7,156.3,145.1,
139.2,133.9,129.0,128.7,128.5,126.9,125.0,124.9,115.6,113.7,113.6,113.4,
113.3,110.3,110.0,104.5,104.2；HRMS(ESI):m/z[M+Na]+calcd for C25H17FN2Na:
387.1268；found:387.1271.
Embodiment 33
Compound 1b (1.0mmol, 177mg), compound 2h (0.5mmol, 81.6mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and Isosorbide-5-Nitrae-dioxane (2mL), are subsequently placed in 110 DEG C of oil baths
In be stirred to react 12h.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, later organic phase mass concentration
For 10% Na2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel post separation
(petrol ether/ethyl acetate=10/1, v/v) obtains white solid product 3s (123.7mg, 68%).The characterization number of the compound
According to as follows:1H NMR(400MHz,DMSO-d6):δ(ppm)11.87(s,1H),8.37–8.28(m,5H),8.20(s,2H),
8.16-8.09 (m, 1H), 7.57 (t, J=7.6Hz, 4H), 7.49 (t, J=7.2Hz, 2H), 7.38-7.32 (m, 1H), 7.14-
7.06(m,1H)；13C NMR(100MHz,DMSO-d6)δ(ppm)160.2,157.8,156.3,145.1,139.2,137.3,
137.2,129.0,128.7,126.9,121.7,120.7,120.6,115.7,113.6,109.0,108.8,98.4,98.2；
HRMS(ESI):m/z[M+Na]+calcd for C25H17FN2Na:387.1268；found:387.1270.
Embodiment 34
Compound 1b (1.0mmol, 177mg), compound 2i (0.5mmol, 89.8mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and Isosorbide-5-Nitrae-dioxane (2mL), are subsequently placed in 110 DEG C of oil baths
In be stirred to react 12h.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, later organic phase mass concentration
For 10% Na2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel post separation
(petrol ether/ethyl acetate=10/1, v/v) obtains white solid product 3t (123.8mg, 65%).The characterization number of the compound
According to as follows:1H NMR(400MHz,DMSO-d6): δ (ppm) 11.98 (s, 1H), 8.34 (d, J=2.4Hz, 1H), 8.31 (d, J=
8.0Hz, 4H), 8.14 (s, 2H), 8.04 (s, 1H), 7.56 (t, J=7.6Hz, 5H), 7.48 (t, J=7.2Hz, 2H), 7.28-
7.20(m,1H)；13C NMR(100MHz,DMSO-d6)δ(ppm)156.4,144.9,139.2,135.7,129.1,128.7,
128.2,126.9,125.8,125.1,122.0,118.4,115.9,113.9,113.3；HRMS(ESI):m/z[M+Na]+
calcd for C25H17ClN2Na:403.0972；found:403.0976.
Embodiment 35
Compound 1b (1.0mmol, 177mg), compound 2j (0.5mmol, 89.8mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and Isosorbide-5-Nitrae-dioxane (2mL), are subsequently placed in 110 DEG C of oil baths
In be stirred to react 12h.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, later organic phase mass concentration
For 10% Na2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel post separation
(petrol ether/ethyl acetate=10/1, v/v) obtains white solid product 3u (112.4mg, 59%).The characterization number of the compound
According to as follows:1H NMR(400MHz,DMSO-d6): δ (ppm) 11.98 (s, 1H), 8.34 (d, J=2.4Hz, 1H), 8.31 (d, J=
8.0Hz, 4H), 8.14 (s, 2H), 8.04 (s, 1H), 7.56 (t, J=7.6Hz, 5H), 7.48 (t, J=7.2Hz, 2H), 7.28-
7.20(m,1H)；13C NMR(100MHz,DMSO-d6)δ(ppm)156.4,144.9,139.2,135.7,129.1,128.7,
128.2,126.9,125.8,125.1,122.0,118.4,115.9,113.9,113.3；HRMS(ESI):m/z[M+Na]+
calcd for C25H17ClN2Na:403.0972；found:403.0976.
Embodiment 36
In 25mL seal pipe be added compound 1b (1.0mmol, 177mg), compound 2k (0.5mmol, 101.6mg),
Elemental iodine (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and Isosorbide-5-Nitrae-dioxane (2mL), are subsequently placed in 110 DEG C of oil
12h is stirred to react in bath.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, organic phase quality is dense later
The Na that degree is 10%2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silicagel column point
White solid product 3v (82.8mg, 41%) is obtained from (petrol ether/ethyl acetate=10/1, v/v).The characterization number of the compound
According to as follows:1H NMR(400MHz,DMSO-d6): δ (ppm) 12.19 (s, 1H), 8.53 (d, J=2.4Hz, 1H), 8.32 (d, J=
7.6Hz, 4H), 8.23-8.17 (m, 4H), 7.85-7.81 (m, 1H), 7.57 (t, J=7.4Hz, 4H), 7.49 (t, J=
7.2Hz,2H),3.89(s,3H)；13C NMR(100MHz,DMSO-d6)δ(ppm)167.0,156.4,144.8,139.1,
136.5,130.2,129.1,128.8,128.2,126.9,122.9,121.1,119.4,115.9,114.1,113.9,52.0；
HRMS(ESI):m/z[M+H]+calcd for C27H21N2O2:405.1598；found:405.1596.
Embodiment 37
Compound 1b (1.0mmol, 177mg), compound 2l (0.5mmol, 95mg), iodine list are added in 25mL seal pipe
Matter (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and Isosorbide-5-Nitrae-dioxane (2mL), are subsequently placed in 110 DEG C of oil baths
It is stirred to react 12h.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, organic phase is with mass concentration later
10% Na2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel post separation (stone
Oily ether/ethyl acetate=10/1, v/v) obtain white solid product 3w (138.8mg, 71%).The characterize data of the compound is such as
Under:1H NMR(400MHz,DMSO-d6): δ (ppm) 12.47 (s, 1H), 8.58 (d, J=8.0Hz, 1H), 8.40 (d, J=
2.8Hz, 1H), 8.36-8.30 (m, 4H), 8.25-8.18 (m, 3H), 7.56 (t, J=7.4Hz, 4H), 7.48 (t, J=
7.2Hz, 2H), 7.42 (t, J=8.0Hz, 1H)；13C NMR(100MHz,DMSO-d6)δ(ppm)156.4,143.9,139.0,
133.0,129.4,129.3,129.1,129.0,128.7,128.1,127.0,120.2,119.3,116.6,115.3；HRMS
(ESI):m/z[M+H]+calcd for C25H18N3O2:392.1394；found:392.1394.
Embodiment 38
Compound 1b (1.0mmol, 177mg), compound 2m (0.5mmol, 79.6mg), iodine are added in 25mL seal pipe
Simple substance (0.5mmol, 127mg), pyridine (0.5mmol, 39.6mg) and Isosorbide-5-Nitrae-dioxane (2mL), are subsequently placed in 110 DEG C of oil baths
In be stirred to react 12h.50mL water quenching reaction is added, (50mL × 3) are extracted with ethyl acetate, later organic phase mass concentration
For 10% Na2S2O3Solution and saturated salt solution successively wash, and anhydrous sodium sulfate is dry.Filtering, is spin-dried for, and crosses silica gel post separation
(petrol ether/ethyl acetate=10/1, v/v) obtains white solid product 3x (124.2mg, 69%).The characterization number of the compound
According to as follows:1H NMR(400MHz,CDCl3): δ (ppm) 8.32 (d, J=7.6Hz, 4H), 8.15 (d, J=7.6Hz, 1H), 8.02
(s, 2H), 7.63 (t, J=7.4Hz, 4H), 7.58-7.52 (m, 2H), 7.47-7.34 (m, 4H), 3.79 (s, 3H)；13C NMR
(100MHz,CDCl3)δ(ppm)157.1,144.7,139.8,137.6,128.7,128.6,128.0,127.0,125.6,
122.3,120.6,119.7,116.5,114.1,109.9,32.8；HRMS(ESI):m/z[M+H]+calcd for C26H21N2:
361.1699；found:361.1701.
Embodiment above describes basic principles and main features of the invention and advantage, the technical staff of the industry should
Understand, the present invention is not limited to the above embodiments, and the above embodiments and description only describe originals of the invention
Reason, under the range for not departing from the principle of the invention, various changes and improvements may be made to the invention, these changes and improvements are each fallen within
In the scope of protection of the invention.
Claims (5)
1. a kind of synthetic method of 3- (4- pyridine) Benzazole compounds, it is characterised in that specific steps are as follows: by acetic acid oxime esters
Compound 1 and 3- formyl indole class compound 2 are dissolved in solvent, catalyst and nitrogenous organic base are then added, in seal pipe
In reacted in 100-130 DEG C target product 3- (4- pyridine) Benzazole compounds 3 be made, the reaction equation in the synthetic method
Are as follows:
Wherein R1For phenyl, substituted-phenyl, 2- naphthalene or thienyl, which is 3,4- methylenedioxyphenyl, 3,4- bis-
Chloro phenyl or mono-substituted benzenes base, the substituent group on mono-substituted benzenes base phenyl ring are methyl, methoxyl group, nitro, chlorine or bromine, R2
For hydrogen, methyl, methoxyl group, methoxybenzyl, fluorine, chlorine, carbomethoxy or nitro, R3For hydrogen or methyl, solvent is toluene, chlorobenzene, second
Nitrile, Isosorbide-5-Nitrae-dioxane, tetrahydrofuran or n,N-Dimethylformamide, catalyst be elemental iodine, N- N-iodosuccinimide or
Ammonium iodide, nitrogenous organic base are triethylamine, diethylamine, pyridine, Isosorbide-5-Nitrae-diazabicylo [2.2.2] octane, 1,8- diaza two
11 carbon -7- alkene of ring or quinoline.
2. the synthetic method of 3- (4- pyridine) Benzazole compounds according to claim 1, it is characterised in that: the acetic acid
The molar ratio of oxime ester compound 1,3- formyl indole or derivatives thereof 2, catalyst and nitrogenous organic base is 2:1:1:
1, the charge ratio of acetic acid oxime ester compound 1 and solvent is 1mmol:2mL.
3. a kind of synthetic method of 3- (4- pyridine) Benzazole compounds, it is characterised in that specific steps are as follows: by acetic acid oxime esters
Compound 1l and 3- formyl indole 2a is dissolved in solvent Isosorbide-5-Nitrae-dioxane, and catalyst iodine simple substance and nitrogenous organic is then added
Alkali pyridine reacts in 110 DEG C in seal pipe and target product quinoline -4- Carbox amide 3l is made, in the synthetic method
Reaction equation are as follows:
4. the synthetic method of 3- (4- pyridine) Benzazole compounds according to claim 3, it is characterised in that: the acetic acid
The molar ratio of oxime ester compound 1l, 3- formyl indole 2a, catalyst iodine simple substance and nitrogenous organic base pyridine are 2:1:
1:1, acetic acid oxime ester compound 1l and solvent Isosorbide-5-Nitrae-dioxane charge ratio are 1mmol:2mL.
5. the synthetic method of 3- (4- pyridine) Benzazole compounds according to claim 1 or 3, it is characterised in that the 3-
(4- pyridine) Benzazole compounds 3 are one of following compounds:
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