CN108947995A - A kind of preparation method of polysubstituted dxadiazine derivatives - Google Patents
A kind of preparation method of polysubstituted dxadiazine derivatives Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims abstract description 12
- 238000006243 chemical reaction Methods 0.000 claims abstract description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims abstract description 7
- -1 benzylamine oxime Chemical class 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 7
- 239000012043 crude product Substances 0.000 claims abstract description 7
- 239000002904 solvent Substances 0.000 claims abstract description 6
- WGQKYBSKWIADBV-UHFFFAOYSA-N aminomethyl benzene Natural products NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 claims abstract description 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000011630 iodine Substances 0.000 claims abstract description 4
- 150000003839 salts Chemical class 0.000 claims abstract description 4
- 238000010898 silica gel chromatography Methods 0.000 claims abstract description 3
- 239000000460 chlorine Substances 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- 239000002585 base Substances 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 2
- 238000001311 chemical methods and process Methods 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 6
- 239000000047 product Substances 0.000 abstract description 4
- 238000010189 synthetic method Methods 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- 239000000706 filtrate Substances 0.000 abstract 1
- 229910000450 iodine oxide Inorganic materials 0.000 abstract 1
- 238000000926 separation method Methods 0.000 abstract 1
- 238000003756 stirring Methods 0.000 abstract 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 40
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- 238000001228 spectrum Methods 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 150000002391 heterocyclic compounds Chemical class 0.000 description 2
- 238000003541 multi-stage reaction Methods 0.000 description 2
- VHNYOQKVZQVBLC-RTCGXNAVSA-N (4r,7e,9as)-7-[[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]methylidene]-4-(3,4,5-trifluorophenyl)-1,3,4,8,9,9a-hexahydropyrido[2,1-c][1,4]oxazin-6-one Chemical compound C1([C@@H]2COC[C@@H]3CC\C(C(N32)=O)=C/C=2C=C(C(=CC=2)N2C=C(C)N=C2)OC)=CC(F)=C(F)C(F)=C1 VHNYOQKVZQVBLC-RTCGXNAVSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- MKYLHNLUANALPV-UHFFFAOYSA-N CC(CN/C(/c(cc1)ccc1F)=N\O)(c1ccccc1)O[n]1c(-c(cc2)ccc2F)nc(C2C=CC=CC2)c1 Chemical compound CC(CN/C(/c(cc1)ccc1F)=N\O)(c1ccccc1)O[n]1c(-c(cc2)ccc2F)nc(C2C=CC=CC2)c1 MKYLHNLUANALPV-UHFFFAOYSA-N 0.000 description 1
- OSUPWUQRPLIJKX-UHFFFAOYSA-N N/C(/c(cc1)ccc1F)=N\O Chemical compound N/C(/c(cc1)ccc1F)=N\O OSUPWUQRPLIJKX-UHFFFAOYSA-N 0.000 description 1
- XOIXSZAJFLMMOS-UHFFFAOYSA-N O=C(c1c2cccc1)O[I]2C#Cc1ccccc1 Chemical compound O=C(c1c2cccc1)O[I]2C#Cc1ccccc1 XOIXSZAJFLMMOS-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- MXOQNVMDKHLYCZ-UHFFFAOYSA-N benzamidoxime Chemical compound ON=C(N)C1=CC=CC=C1 MXOQNVMDKHLYCZ-UHFFFAOYSA-N 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 150000002497 iodine compounds Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000003863 metallic catalyst Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 230000008635 plant growth Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- QUJLPICXDXFRSN-UHFFFAOYSA-N scandium;trifluoromethanesulfonic acid Chemical compound [Sc].OS(=O)(=O)C(F)(F)F QUJLPICXDXFRSN-UHFFFAOYSA-N 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910000144 sodium(I) superoxide Inorganic materials 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229940124648 γ-Secretase Modulator Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Steroid Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
The invention discloses a kind of preparation methods for the polysubstituted dxadiazine derivatives for belonging to technical field of organic synthesis.The method are as follows: into reaction vessel, alpha substituted benzylamine oxime, substitutedphenylethynyl base salt compounded of iodine and potassium hydroxide is successively added, solvents tetrahydrofurane is added, at room temperature after stirring to reaction 4 hours, crude product is obtained using Rotary Evaporators concentration filtrate, crude product purified by silica gel column chromatography for separation obtains target compound.The synthetic method of dxadiazine derivatives provided by the invention have it is scientific and reasonable, synthetic method is simple, and reaction condition is mild, and product is easy to the features such as purifying.Its reaction equation is as follows:
Description
Technical field
The invention belongs to technical field of organic synthesis, and in particular to a kind of preparation method of polysubstituted dxadiazine derivatives.
Background technique
Oxadiazines class compound is less exploration containing N, and one of O heterocyclic compound is present in natural products and has
In the molecule of bioactivity.It can be used for treating Alzheimer disease as gamma secretase modulators.((a)
J.Org.Chem.2017,82,2957-2964.(b)J.Med.Chem.2001,44,619.)
Meanwhile there are document report dxadiazine derivatives to have important role in terms of pesticide and plant growth regulating.
(Chemistry Of Heterocyclic Compounds.2017,53(5),495–497.)
In view of extensive bioactivity and application value containing dxadiazine derivatives, synthesize with developing a kind of practicability and effectiveness more
The new method of dxadiazine derivatives is replaced to be of great significance.
In recent years, the method for preparing polysubstituted dxadiazine derivatives has:
1) 2006, Cho seminar developed one kind from oxime, catalyst was made with trifluoromethanesulfonic acid scandium, by two steps
1,2,4- oxadiazines class compound is synthesized.(Tetrahedron Letters.2006,47,9029–9033.)
2) 2017, Matthew G.Bursavich seminar developed it is a kind of from amide, by multistep reaction,
Dxadiazine derivatives are obtained.(J.Med.Chem.2017,60,2383-2400.)
The above method for preparing polysubstituted dxadiazine derivatives, has certain disadvantages: 1) multistep reaction is needed, it is final to produce
Rate is low；2) some metallic catalysts are used；3) reaction time is long.
Summary of the invention
In order to overcome the above-mentioned deficiencies of the prior art, as the supplement to existing dxadiazine derivatives synthetic method, the present invention
Provide a kind of preparation method of polysubstituted dxadiazine derivatives.
A kind of preparation method of polysubstituted dxadiazine derivatives, the compound have structure shown in formula I:
R1Substituent group is selected from fluorine, chlorine, bromine, iodine, ester group, phenyl；R2Substituent group is selected from fluorine, chlorine, bromine；It is characterized in that,
Into reactor, alpha substituted benzylamine oxime and substitutedphenylethynyl base salt compounded of iodine and alkali is added, after being stirred to react in a solvent, uses
Rotary Evaporators are concentrated to get crude product, and crude product uses the isolated target product of silica gel column chromatography, and chemical process is shown in instead
Answer formula II:
The molar ratio of the alpha substituted benzylamine oxime, the high iodine compound of substitutedphenylethynyl base and potassium hydroxide is 1:1.2:
1.5.The solvent is tetrahydrofuran, and reaction temperature is room temperature, reaction time 4h.
The invention has the benefit that the synthetic method of polysubstituted dxadiazine derivatives provided by the invention is scientific and reasonable,
A kind of new approach is provided, the product with a variety of substituent groups, feature have been obtained by this method are as follows: raw material is easy to get, grasps
Make the features such as simple, reaction condition is mild, the reaction time is short.
Detailed description of the invention
Fig. 1 is the NMR spectra of compound 3aa prepared by embodiment 1；
Fig. 2 is the NMR spectra of compound 3da prepared by embodiment 4；
Fig. 3 is the NMR spectra of compound 3ac prepared by embodiment 7.
Specific embodiment
The present invention is described in more detail with specific embodiment with reference to the accompanying drawing:
Test method described in following embodiments is unless otherwise specified conventional method；The reagent and material, such as
Without specified otherwise, commercially obtain.
Embodiment 1
1) preparation of dxadiazine derivatives 3aa
Benzamidoxime 1a (0.3mmol, 40.8mg), 2a (0.36mmol, 125.3mg) and KOH are added in 10mL round-bottomed flask
(0.45mmol,25.2mg).It is added tetrahydrofuran (3mL), is stirred at room temperature, react 4 hours.After completion of the reaction, using rotation
Turn evaporimeter removing solvent and obtain crude product, crude by column chromatography separates (200-300 mesh silica gel) (petrol ether/ethyl acetate
=3/1) solvent, is removed using Rotary Evaporators, obtains target product 3aa, yield 77%.
Spectrum elucidation data 3aa:
1H NMR(500MHz,DMSO-d6) δ 8.00 (s, 1H), 7.86 (d, 1H), 7.81 (d, J=6.4Hz, 2H), 7.75
(d, J=6.9Hz, 2H), 7.56-7.43 (m, 5H), 7.39 (d, J=7.2Hz, 2H), 7.30-7.20 (m, 4H), 7.18-7.09
(m, 3H), 6.97 (d, J=7.2Hz, 2H), 4.42-4.32 (m, 1H), 3.58 (d, J=12.9Hz, 1H)13C NMR
(125MHz,DMSO-d6)δ152.97,142.25,135.11,134.18,133.34,132.02,130.95,130.15,
129.00,128.57,128.24,128.01,127.48,127.09,126.84,125.83,124.57,116.24,101.13,
44.41.HRMS(ESI)m/z calcd for C30H25N4O2 +(M+H)+473.1978,found 473.1974.
Embodiment 2
The 1a in example 1 is replaced with 1b, for other conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3ba:
1H NMR(500MHz,DMSO-d6) δ 8.03 (d, J=5.1Hz, 1H), 7.84 (dd, J=8.5,5.5Hz, 2H),
7.76-7.71 (m, 3H), 7.50 (dd, J=8.5,5.7Hz, 2H), 7.36 (dt, J=19.5,8.2Hz, 4H), 7.25-7.15
(m, 4H), 7.05 (dt, J=12.6,8.3Hz, 4H), 4.40 (dd, J=13.1,5.8Hz, 1H), 3.58 (d, J=13.0Hz,
1H).13C NMR(125MHz,DMSO-d6)δ152.07,135.10,134.10,130.32,129.66,129.17,129.12,
(129.02,128.38,128.12,125.88,125.59,124.59,116.03 d, J=15.5Hz), 115.80,115.23
(d, J=21.0Hz), 44.16.HRMS (ESI) m/z calcd for C30H23F2N4O2 +(M+H)+509.1789,found
509.1789.
Embodiment 3
The 1a in example 1 is replaced with 1c, for other conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3ca:
1H NMR(500MHz,DMSO-d6) δ 8.05 (d, J=4.9Hz, 1H), 7.77 (d, J=8.4Hz, 2H), 7.71 (d,
J=7.7Hz, 2H), 7.67 (s, 1H), 7.58-7.49 (m, 4H), 7.37 (t, J=7.6Hz, 2H), 7.28 (d, J=8.4Hz,
2H), 7.23 (t, J=7.3Hz, 4H), 7.07 (t, J=7.7Hz, 2H), 4.41 (dd, 1H), 3.57 (d, J=13.1Hz, 1H)
.13C NMR(125MHz,DMSO-d6)δ151.86,141.34,135.64,135.32,133.98,133.65,133.16,
130.66,130.41,129.01,128.45,128.37,128.20,127.79,127.22,125.94,124.60,116.24,
101.51,44.08.HRMS(ESI)m/z calcd for C30H23Cl2N4O2 +(M+H)+541.1198,found 541.1196.
Embodiment 4
The 1a in example 1 is replaced with 1d, for other conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3da:
1H NMR(500MHz,DMSO-d6) δ 8.09 (d, J=5.3Hz, 1H), 7.74-7.68 (m, 6H), 7.66 (s, 1H),
7.47 (d, J=8.6Hz, 2H), 7.43 (d, J=8.6Hz, 2H), 7.38 (t, J=7.7Hz, 2H), 7.27-7.22 (m, 4H),
7.09 (t, J=7.8Hz, 2H), 4.43 (dd, J=13.2,5.9Hz, 1H), 3.58 (d, J=13.1Hz, 1H)13C NMR
(125MHz,DMSO-d6) δ 151.92,141.42,135.38,133.87 (d, J=27.6Hz), 131.86,131.15 (d, J=
32.3Hz), 130.42,129.13 (d, J=29.9Hz), 128.42 (d, J=52.4Hz), 127.22,125.96,124.51
(d, J=23.2Hz), 121.87,116.22,101.58,44.11.HRMS (ESI) m/z calcd for C30H23Br2N4O2 +(M
+H)+629.0188,found 629.0182.
Embodiment 5
The 1a in example 1 is replaced with 1e, for other conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3ea:
1H NMR(500MHz,DMSO-d6) δ 8.04 (d, J=5.1Hz, 1H), 7.86 (d, J=8.5Hz, 2H), 7.73-
7.68 (m, 2H), 7.64-7.58 (m, 3H), 7.52 (d, J=8.5Hz, 2H), 7.40-7.32 (m, 4H), 7.29-7.22 (m,
4H), 7.13-7.07 (m, 2H), 4.41 (dd, J=13.3,5.9Hz, 1H), 3.56 (d, J=12.7Hz, 1H)13C NMR
(125MHz,DMSO-d6)δ152.14,141.66,137.76,137.19,135.41,134.03,133.90,131.39,
130.47,129.27,129.07,128.57,128.52,128.29,127.28,126.03,124.65,116.26,101.65,
98.12,95.09,44.17.HRMS(ESI)m/z calcd for C30H23F2N4O2 +(M+H)+724.9910,found
724.9909.
Embodiment 6
The 2a in example 1 is replaced with 2b, for other conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3ab:
1H NMR(500MHz,DMSO-d6) δ 8.03 (d, J=5.3Hz, 1H), 7.87 (s, 1H), 7.86-7.79 (m, 4H),
7.56-7.49 (m, 3H), 7.44 (dd, J=6.5,2.9Hz, 2H), 7.31-7.27 (m, 3H), 7.21 (t, J=8.8Hz, 2H),
7.12 (dd, J=8.7,5.4Hz, 2H), 6.75 (t, J=8.8Hz, 2H), 4.42 (dd, J=13.1,5.9Hz, 1H), 3.60
(d, J=13.0Hz, 1H)13C NMR(125MHz,DMSO-d6) δ 163.10 (d, J=246.5Hz), 161.59 (d, J=
242.4Hz),153.03,142.30,134.36,131.98,130.99,130.72,129.50,128.97,128.84,
(128.69,128.22,127.43,126.91,126.56,116.25,115.82 d, J=21.3Hz), 114.81 (d, J=
21.5Hz),100.75,44.05.HRMS(ESI)m/z calcd for C30H23F2N4O2 +(M+H)+509.1789,found
509.1784.
Embodiment 7
The 2a in example 1 is replaced with 2c, for other conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3ac:
1H NMR(500MHz,DMSO-d6) δ 8.04 (d, J=5.3Hz, 1H), 7.92 (s, 1H), 7.85-7.78 (m, 4H),
7.56-7.49 (m, 3H), 7.45-7.37 (m, 4H), 7.29 (t, J=6.2Hz, 3H), 7.05 (d, J=8.6Hz, 2H), 6.95
(d, J=8.5Hz, 2H), 4.40 (dd, J=13.1,5.8Hz, 1H), 3.58 (d, J=13.0Hz, 1H)13C NMR(125MHz,
DMSO-d6)δ153.13,142.52,135.17,134.08,133.05,131.98,131.41,131.02,128.98,
128.80,128.73,128.18,127.94,127.69,127.51,126.94,126.36,116.88,100.83,
43.87.HRMS(ESI)m/z calcd for C30H23Cl2N4O2 +(M+H)+541.1198,found 541.1196.
Embodiment 8
The 2a in example 1 is replaced with 2d, for other conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3ad:
1H NMR(500MHz,DMSO-d6) δ 8.05 (d, J=5.3Hz, 1H), 7.93 (s, 1H), 7.85-7.81 (m, 2H),
7.74 (d, J=8.4Hz, 2H), 7.53 (ddd, J=19.6,10.5,5.2Hz, 5H), 7.41-7.37 (m, 2H), 7.30 (q, J
=6.8,6.1Hz, 3H), 4.39 (dd, J=13.1,5.8Hz, 1H), 3.59 (d, J=13.1Hz, 1H)13C NMR(125MHz,
DMSO-d6)δ153.15,142.58,134.13,133.44,132.44,131.95,131.88,131.00,130.88,
128.96,128.80,128.76,128.17,127.90,127.54,126.92,126.70,124.03,119.88,116.89,
100.96,43.87.HRMS(ESI)m/z calcd for C30H23Br2N4O2 +(M+H)+629.0188,found 629.0181.
Embodiment 9
The 1a in example 6 is replaced with 1f, for other conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3fb:
1H NMR(500MHz,DMSO-d6) δ 8.21 (d, J=5.3Hz, 1H), 8.01 (d, J=8.3Hz, 2H), 7.87 (d,
J=8.3Hz, 2H), 7.84-7.75 (m, 4H), 7.70-7.64 (m, 3H), 7.29 (dd, J=8.5,5.5Hz, 2H), 7.20 (t,
J=8.8Hz, 2H), 6.87 (t, J=8.7Hz, 2H), 4.49 (dd, J=13.2,5.8Hz, 1H), 3.88 (s, 3H), 3.83 (s,
3H), 3.57 (d, J=13.0Hz, 1H)13C NMR(125MHz,DMSO-d6) δ 166.14,163.27 (d, J=247.9Hz),
161.74 (d, J=243.5Hz), 151.83,141.42,135.97,135.04,132.97,131.54,130.39,129.99,
(129.52,129.17 d, J=21.0Hz), 128.55,128.48,127.29,126.94,126.72,126.65,116.55,
115.84 (d, J=21.4Hz), 115.18 (d, J=21.8Hz), 101.45,52.73,52.47,43.86.HRMS (ESI) m/z
calcd for C34H26F2N4NaO2 +(M+Na)+647.1718,found 647.1716.
Embodiment 10
The 1a in example 6 is replaced with 1g, for other conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3gb:
1H NMR(500MHz,DMSO-d6) δ 8.12 (d, J=5.8Hz, 1H), 7.91 (d, J=8.0Hz, 2H), 7.85-
7.77 (m, 5H), 7.69 (dd, J=21.6,7.6Hz, 4H), 7.60 (t, J=6.0Hz, 4H), 7.49 (q, J=8.1Hz, 4H),
7.40 (dt, J=14.1,7.3Hz, 2H), 7.29-7.21 (m, 4H), 6.81 (t, J=8.6Hz, 2H), 4.48 (dd, J=
13.2,5.8Hz, 1H), 3.64 (d, J=12.9Hz, 1H)13C NMR(125MHz,DMSO-d6) δ 163.17 (d, J=
247.2Hz), 161.63 (d, J=243.3Hz), 152.57,142.52,142.15,140.28,140.02,139.65,
134.51,130.86,130.72,129.91,129.41,128.45,128.35,128.04,127.95,127.35,127.18,
(127.09,127.00,126.60,126.51,116.23,115.84 d, J=21.4Hz), 114.94 (d, J=21.5Hz),
101.09,44.08.HRMS(ESI)m/z calcd for C42H31F2N4O2 +(M+H)+661.2415,found 661.2425.
Table 1
Claims (3)
1. a kind of preparation method of polysubstituted dxadiazine derivatives, the compound has structure shown in formula I:
R1Substituent group is selected from fluorine, chlorine, bromine, iodine, ester group, phenyl；R2Substituent group is selected from fluorine, chlorine, bromine；It is characterized in that, to anti-
It answers in device, alpha substituted benzylamine oxime and substitutedphenylethynyl base salt compounded of iodine and alkali is added, after being stirred to react in a solvent, uses rotation
Evaporimeter is concentrated to get crude product, and crude product uses the isolated type I compound of silica gel column chromatography, and chemical process is shown in reaction equation
II:
2. preparation method according to claim 1, it is characterised in that: alpha substituted benzylamine oxime and substitutedphenylethynyl base salt compounded of iodine and
The molar ratio of potassium hydroxide is 1:1.2:1.5.
3. preparation method described in accordance with the claim 1, it is characterised in that: tetrahydrofuran, reaction temperature room temperature, reaction time is
4 hours.
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