CN110041290A - 2,5- dihydro -1,4,5- sulphur phenodiazine Zhuo and its oxide preparation method - Google Patents
2,5- dihydro -1,4,5- sulphur phenodiazine Zhuo and its oxide preparation method Download PDFInfo
- Publication number
- CN110041290A CN110041290A CN201910258698.XA CN201910258698A CN110041290A CN 110041290 A CN110041290 A CN 110041290A CN 201910258698 A CN201910258698 A CN 201910258698A CN 110041290 A CN110041290 A CN 110041290A
- Authority
- CN
- China
- Prior art keywords
- sulphur
- nmr
- dihydro
- target compound
- cdcl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000005864 Sulphur Substances 0.000 title claims abstract description 24
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- 150000001875 compounds Chemical class 0.000 claims abstract description 52
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims abstract description 22
- 230000003647 oxidation Effects 0.000 claims abstract description 12
- 238000007254 oxidation reaction Methods 0.000 claims abstract description 12
- 229910000029 sodium carbonate Inorganic materials 0.000 claims abstract description 11
- 239000003513 alkali Substances 0.000 claims abstract description 6
- -1 hydrazone compounds Chemical group 0.000 claims abstract description 6
- 239000007800 oxidant agent Substances 0.000 claims abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 72
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 23
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 22
- 238000006243 chemical reaction Methods 0.000 claims description 18
- 125000001424 substituent group Chemical group 0.000 claims description 13
- 239000000376 reactant Substances 0.000 claims description 12
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 claims description 11
- 239000003208 petroleum Substances 0.000 claims description 11
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims description 9
- 239000011541 reaction mixture Substances 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 9
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims description 7
- 239000003480 eluent Substances 0.000 claims description 7
- 239000002585 base Substances 0.000 claims description 6
- 238000010828 elution Methods 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 239000011737 fluorine Substances 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 125000003107 substituted aryl group Chemical group 0.000 claims description 5
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 239000012046 mixed solvent Substances 0.000 claims description 4
- 238000010898 silica gel chromatography Methods 0.000 claims description 4
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 1
- 125000001246 bromo group Chemical group Br* 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 230000001590 oxidative effect Effects 0.000 claims 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract description 12
- 238000000034 method Methods 0.000 abstract description 8
- 229910052717 sulfur Chemical group 0.000 abstract description 8
- 239000011593 sulfur Chemical group 0.000 abstract description 8
- 239000003814 drug Substances 0.000 abstract description 7
- 229940079593 drug Drugs 0.000 abstract description 6
- WSEQJBLCPNXOAI-UHFFFAOYSA-N 2,5-dihydro-1,4,5-thiadiazepine Chemical compound S1CC=NNC=C1 WSEQJBLCPNXOAI-UHFFFAOYSA-N 0.000 abstract description 4
- 150000003839 salts Chemical class 0.000 abstract description 4
- 238000011160 research Methods 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 139
- 239000000047 product Substances 0.000 description 57
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 51
- 238000005160 1H NMR spectroscopy Methods 0.000 description 51
- 239000007787 solid Substances 0.000 description 48
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 25
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 8
- 238000001228 spectrum Methods 0.000 description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000001819 mass spectrum Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000005311 nuclear magnetism Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 230000006837 decompression Effects 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- IGRCWJPBLWGNPX-UHFFFAOYSA-N 3-(2-chlorophenyl)-n-(4-chlorophenyl)-n,5-dimethyl-1,2-oxazole-4-carboxamide Chemical compound C=1C=C(Cl)C=CC=1N(C)C(=O)C1=C(C)ON=C1C1=CC=CC=C1Cl IGRCWJPBLWGNPX-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 150000007857 hydrazones Chemical class 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000002390 rotary evaporation Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- NLJRARZQPGDYSK-IRXDYDNUSA-N (2s)-2-[[(2s)-3-hydroxy-2-[(4-methylphenyl)sulfonylamino]propanoyl]amino]-3-(4-hydroxyphenyl)propanoic acid Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 NLJRARZQPGDYSK-IRXDYDNUSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- NEHMKBQYUWJMIP-UHFFFAOYSA-N anhydrous methyl chloride Natural products ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- MGNKFTJFQNDWQM-UHFFFAOYSA-N methyl 2-[[4-(3-bromo-4-hydroxy-5-methoxyphenyl)-5-cyano-2-oxo-3,4-dihydro-1h-pyridin-6-yl]sulfanyl]acetate Chemical compound C1C(=O)NC(SCC(=O)OC)=C(C#N)C1C1=CC(Br)=C(O)C(OC)=C1 MGNKFTJFQNDWQM-UHFFFAOYSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000001741 organic sulfur group Chemical group 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000010970 precious metal Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/36—Seven-membered rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
The main purpose of the present invention is to provide the preparation methods of a kind of completely new 2,5- dihydro -1,4,5- sulphur phenodiazine tall and erect (2,5-dihydro-1,4,5-thiadiazepine) and its oxide.The method achieve by alpha-halogenate hydrazone compounds and sulfur-bearing inner salt, under conditions of sodium carbonate makees alkali, synthesis 2 that a step is simple and efficient, 5- dihydro-Isosorbide-5-Nitrae, 5- sulphur phenodiazine are tall and erect, simultaneously by control oxidising agent equivalent, can a step obtain the oxidation product of different oxidation state.It may be a kind of good drug leads molecule in view of such compound, there is good drug research value.
Description
Technical field
The invention belongs to the field of chemical synthesis, and in particular to 2,5- of one kind dihydro-Isosorbide-5-Nitrae, 5- sulphur phenodiazine Zhuo (2,5-
) and its preparation method of oxide dihydro-1,4,5-thiadiazepine.
Background technique
Nitrogen and element sulphur are widely present in nature and organism, nitrogenous compound it is representative be exactly day
Right organic-biological alkali, has extremely important effect in field of medicaments；Sulfur-containing compound is then widely used in material, drug
Even in food.Heptatomic ring pastern bone frame succinctly efficiently constructs heptatomic ring system there are in many natural products and drug molecule skeleton
Always one of organic chemist and the emphasis of pharmaceutical chemists research.We are not yet ground by the way that one kind is novel
Study carefully the sulfur-bearing inner salt and common alpha-halogenate hydrazone reaction of exploitation, a step is efficiently constructed comprising four substituent groups and three hetero atoms
Heptatomic ring system, wherein four substituent groups can be with further progress function dough, to obtain a series of particular functional dough
Compound, this kind of molecule are expected to become useful drug leads (Merta, B.D.*and Elattarb, K.M.Seven-
membered Rings with Three Heteroatoms:Chemistry of 1,2,5-and 1,4,5-
Thiadiazepines,Current Organic Chemistry,2018,22,386-410)。
The sulfur-containing compound of different oxidation states can show different physicochemical property and bioactivity, especially medical
Field and advanced material field, the oxidation state for changing element sulphur in sulfur-containing compound tend to significantly improve pharmaceutical activity and material
Expect performance, and mutually converting between element sulphur difference oxidation state is the research emphasis of drug pharmacological effect, efficient selective
Oxidation sulfur-containing organic compound have great importance.
Summary of the invention
The main purpose of the present invention is to provide a kind of completely new 2,5- dihydro -1,4,5- sulphur phenodiazine Zhuo (2,5-
) and its preparation method of oxide dihydro-1,4,5-thiadiazepine.The method achieve by alpha-halogenate hydrazone class chemical combination
Object and sulfur-bearing inner salt, under conditions of sodium carbonate makees alkali, the synthesis 2 that a step is simple and efficient, 5- dihydro-Isosorbide-5-Nitrae, 5- sulphur phenodiazine
Zhuo, while only can aoxidize to obtain the oxidation product of different oxidation state by a step by control oxidising agent equivalent.
Compound of the present invention be as in formula 1 I compound represented -2,5- dihydro -1,4,5- sulphur phenodiazine it is tall and erect (2,
5-dihydro-1,4,5-thiadiazepine) and its oxide II and III.
Wherein: R1For substituted aryl substituent group (on phenyl ring replace include 4- methoxyl group, 4- methyl, 4- nitro, 4- cyano,
4- trifluoromethyl, 4- fluorine, 4- chlorine, 4- bromine), 1- naphthyl substituted base, 2- furyl substituent, alkyl substituent, alkenyl group；R2
For acetyl group or tertbutyloxycarbonyl substituent group；R3For methyl substituents or ethyl substituent.
2,5- dihydro -1,4,5- sulphur phenodiazine of the invention tall and erect (2,5-dihydro-1,4,5-thiadiazepine) and its
The preparation method of oxide is as shown in Equation 2:
Compound shown in compound shown in general formulae IV, general formula V and powdered sodium carbonate are dissolved in two at room temperature
In chloromethane alkane solvents, reactant IV disappears completely, and organic solvent will be removed under reaction mixture reduced pressure, and column chromatographic elution obtains
To target compound I, in reactant IV: wherein R1For substituted aryl substituent group, (replace on phenyl ring includes 4- methoxyl group, 4- first
Base, 4- nitro, 4- cyano, 4- trifluoromethyl, 4- fluorine, 4- chlorine, 4- bromine), 1- naphthyl substituted base, 2- furyl substituent, alkyl takes
Dai Ji, alkenyl group；R2For acetyl group or tertbutyloxycarbonyl substituent group；R3For methyl substituents or ethyl substituent.
The preparation method of target compound II: i.e. by m-CPBA (the m-chloro peroxide of compound shown in general formula I and appropriate equivalent
Benzoic acid) it is dissolved in dichloromethane solvent at room temperature, reactant I disappears completely, by reaction mixture reduced pressure
Lower removing organic solvent, column chromatographic elution obtain target compound II, in reactant I: wherein R1For substituted aryl substituent group (benzene
Replace on ring includes 4- methoxyl group, 4- methyl, 4- nitro, 4- trifluoromethyl, 4- fluorine), 2- furyl substituent, alkyl substituent,
Alkenyl group；R2For acetyl group or tertbutyloxycarbonyl substituent group；R3For methyl substituents or ethyl substituent.
The preparation method of target compound III: i.e. by compound shown in general formula I and appropriate excessive m-CPBA (m-chloro peroxide
Benzoic acid) it is dissolved in dichloromethane solvent at room temperature, reactant I disappears completely, by reaction mixture reduced pressure
Lower removing organic solvent, column chromatographic elution obtain target compound III, in reactant I: wherein R1For substituted aryl substituent group (benzene
Replace on ring includes 4- methoxyl group, 4- methyl, 4- trifluoromethyl, 4- fluorine), 2- furyl substituent, alkyl substituent, alkenyl substitution
Base；R2For acetyl group or tertbutyloxycarbonyl substituent group；R3For methyl substituents.
Currently preferred 2,5- dihydro -1,4,5- sulphur phenodiazine is tall and erect (2,5-dihydro-1,4,5-thiadiazepine)
Preparation method be to use sodium carbonate as alkali, using methylene chloride as solvent.
Further, currently preferred preparation method is: compounds Ⅳ, compound V rub with carbonate reagent when reaction
You are IV: V than (i.e. equivalent proportion): sodium carbonate=1.0:1.5:2.0, and dichloromethane solution concentration is 0.1M, i.e., 0.1 mole every
It rises.
Further, for currently preferred preparation method in silica gel column chromatography, eluent used is petroleum ether and second
The mixed solvent of acetoacetic ester, and volume ratio VPetroleum ether:VEthyl acetate=5:1~2:1.
Method of the present invention is the introducing reagent for using a kind of novel organic sulfur-containing inner salt for the first time as sulphur atom,
Reagent preparation is convenient, and the foul odour having without commonly using sulfur-bearing regent；Contain in another raw material simultaneously there are two nitrogen-atoms,
This makes a step of the invention just construct the heteroatomic heptatomic ring containing there are three, may have good bioactivity, so as to
It can obtain a kind of completely new drug leads molecule.
Method of the present invention can be easy to prepare 2,5- dihydro -1,4,5- sulphur phenodiazine Zhuo (2,5-dihydro-
Isosorbide-5-Nitrae, 5-thiadiazepine) and its oxide, raw material be easy to get, do not use precious metal reagent, operation is simple, after
Processing is convenient, and yield is generally very high, and is not necessarily to inert gas shielding during the preparation process, and reaction condition is mild, can be in room temperature (25
DEG C) go on smoothly reaction, it is easy to accomplish a large amount of preparations.
Detailed description of the invention
Attached drawing 1-6 is respectively the obtained product I -1 of the embodiment of the present invention, II -2 and III -3 nuclear magnetic spectrogram (hydrogen spectrum
It is composed with carbon).
Specific embodiment
The present invention is explained below in conjunction with specific embodiment.
It is the most preferred embodiment of prepare compound of the present invention below.In following all examples, nuclear-magnetism spectrum detection passes through
400 and Varian of Varian 300, Bruker 400, JEOL, 600 MHz instrument is in CDCl3、(CD3)2CO or d6-DMSO
Middle acquisition.δ value is internal standard relative value (CDCl3Calibrate δ 7.261H NMR and 77.0013C NMR；(CD3)2CO calibrates δ 2.051H NMR and 29.8413C NMR；d6-DMSOδ2.50 1H NMR and 39.5213C NMR).High resolution mass spectrum (HRMS) passes through
4G quadrupole time-of-flight (QTof) mass spectrometer obtains.
Embodiment 1
The reaction equation of embodiment 1, specifically used compounds Ⅳ -1 and compound V -1 and I -1 structure of product are shown in formula 3.
Experiment shows that currently preferred alkali is sodium carbonate, and preferred organic solvent is methylene chloride, the highest yield of reaction product
Be 98%, best material molar ratio be compounds Ⅳ: compound V: carbonate reagent=1.0:1.5:2.0, solution it is optimal
Concentration is 0.1M.
Specific experiment step is: by the compounds Ⅳ -1 of 76mg (0.30mmol, 1.0 equivalents) and 114mg (0.450mmol,
1.5 equivalents) compound V -1 be dissolved in the methylene chloride of 3mL, be added 64mg (0.60mmol, 2.0 equivalents) sodium carbonate, in
25 DEG C of reactions.Thin-layer chromatography monitoring reactant IV -1 has disappeared, and by reaction mixture, rotary evaporation removing is molten under water pump decompression
Agent methylene chloride.Residue is with 200-300 mesh silica gel, eluent (volume ratio VPetroleum ether:VEthyl acetate=5:1~2:1) column chromatographs to obtain
Compound 102mg shown in I -1, product by nuclear-magnetism (hydrogen spectrum, carbon spectrum), high resolution mass spectrum identification, and I -1 by monocrystalline into one
It walks and determines its structure.
Product I -1 is yellow solid, yield 98%；Fusing point: 192.8-193.1 DEG C of1H NMR(400MHz,CDCl3)δ
7.91 (d, J=7.6Hz, 2H), 7.56 (t, J=7.2Hz, 1H), 7.47 (t, J=7.2Hz, 2H), 4.27 (s, 2H), 3.74
(s,3H),3.73(s,3H),2.12(s,3H)；13C NMR(100MHz,CDCl3)δ171.0,170.8,163.9,162.9,
132.6,132.2,129.9,129.8,128.9,127.4,53.2,52.7,25.5,21.6；ESI-HRMS m/z calcd
for C16H16N2O5S+H+349.0853, found 349.0855. mono-crystalline structures are stored in Cambridge crystal data library, monocrystalline storage
Number: CCDC 1885455.
Prepare method and implementation used in the embodiment of other compounds of the invention (chemical compounds I -2 to chemical compounds I -24)
Example 1 is identical, and reaction condition is as follows: compounds Ⅳ (0.3mmol), compound V (1.5 equivalent) are dissolved in the methylene chloride of 3mL,
Addition sodium carbonate amount is 64mg (0.60mmol, 2.0 equivalents), 25 DEG C of room temperature reactions.
Embodiment 2
The reaction equation of embodiment 2, specifically used chemical compounds I -1 and II -1 structure of product are shown in formula 4.
Specific experiment step is: by the chemical compounds I -1 of 105mg (0.300mmol, 1.0 equivalents) and 61mg (0.30mmol,
1.0 equivalents) m-CPBA (85%, metachloroperbenzoic acid) be dissolved in the methylene chloride of 3mL, in 25 DEG C react.Thin-layer chromatography
Monitoring reactant I -1 has disappeared, and reaction mixture is rotated evaporation of solvent methylene chloride under water pump decompression.Residue with
200-300 mesh silica gel, eluent (volume ratio VPetroleum ether:VEthyl acetate=3:1~1:1) column chromatographs to obtain compound 81mg shown in II -1,
Its product is by nuclear-magnetism (hydrogen spectrum, carbon spectrum), high resolution mass spectrum identification.
Product II -1 is white solid, yield 74%；Fusing point: 123.9-124.6 DEG C of1H NMR(400MHz,CDCl3)δ
7.91 (d, J=7.2Hz, 2H), 7.56 (t, J=7.2Hz, 1H), 7.48 (t, J=7.2Hz, 2H), 4.49 (d, J=13.6Hz,
1H), 4.30 (d, J=13.2Hz, 1H), 3.85 (s, 3H), 3.84 (s, 3H), 2.38 (s, 3H)；13C NMR(100MHz,
CDCl3)δ172.5,166.0,163.0,162.3,140.3,134.3,132.5,129.0,127.8,53.5,48.0,22.3,
(2C missing)；ESI-HRMS m/z calcd for C16H16N2O6S+Na+ 387.0621,found 387.0620.
Prepare method and reality used in the embodiment of other compounds of the invention (compound ii -2 to compound ii -15)
Apply that example 2 is identical, and reaction condition is as follows: chemical compounds I (0.3mmo) l and m-CPBA (metachloroperbenzoic acid, 1.0 equivalents) are dissolved in
In the methylene chloride of 3mL, 25 DEG C of room temperature reactions.
Embodiment 3
The reaction equation of embodiment 3, specifically used chemical compounds I -1 and III -1 structure of product are shown in formula 5.
Specific experiment step is: by the chemical compounds I -1 of 105mg (0.3mmol, 1.0 equivalents) and 183mg (0.9mmol, 3.0
Equivalent) m-CPBA (85%, metachloroperbenzoic acid) be dissolved in the methylene chloride of 3mL, in 25 DEG C react.Thin-layer chromatography monitoring
Reactant I -1 has disappeared, and reaction mixture is diluted with methylene chloride, and the sodium bicarbonate solution 10mL of saturation is added, and water phase is used
Methylene chloride extracts three times, merges organic phase, and dry with anhydrous sodium sulfate, and rotary evaporation removes organic molten under water pump decompression
Agent methylene chloride.Residue is with 200-300 mesh silica gel, eluent (volume ratio VPetroleum ether:VEthyl acetate=10:1~3:1) column chromatographs
To compound 75mg shown in III -1, product is by nuclear-magnetism (hydrogen spectrum, carbon spectrum), high resolution mass spectrum identification, and III -1 by monocrystalline
Further determine that its structure.
Product III -1 is white solid, yield 66%；Fusing point: 185.3-185.9 DEG C of1H NMR(400MHz,CDCl3)δ
7.99 (d, J=7.2Hz, 2H), 7.62 (t, J=7.2Hz, 1H), 7.53 (t, J=7.2Hz, 2H), 4.74 (s, 2H), 3.86
(s,3H),3.84(s,3H),2.35(s,3H)；13C NMR(100MHz,CDCl3)δ172.6,163.0,161.8,160.4,
142.6,133.2,131.8,129.2,128.3,54.5,53.8,53.7,22.4,(1C missing)；ESI-HRMS m/z
calcd for C16H16N2O7S+Na+403.0570, found 403.0565. mono-crystalline structures are stored in Cambridge crystal data library, single
Crystalline substance storage number: CCDC 1887981.
Prepare method and reality used in the embodiment of other compounds of the invention (compound III -2 to compound III -9)
Apply that example 3 is identical, and reaction condition is as follows: chemical compounds I (0.3mmol) and m-CPBA (metachloroperbenzoic acid, 3.0 equivalents) are dissolved in
In the methylene chloride of 3mL, 25 DEG C of room temperature reactions.
Products therefrom structure and data are characterized as below:
Product I -2 is yellow solid, yield 89%；Fusing point: 71.8-72.4 DEG C of1H NMR(400MHz,CDCl3)δ
7.87 (d, J=8.8Hz, 2H), 6.95 (d, J=8.8Hz, 2H), 4.24 (s, 2H), 3.84 (s, 3H), 3.73 (s, 3H), 3.71
(s,3H),2.08(s,3H)；13C NMR(100MHz,CDCl3)δ170.8,170.7,163.9,163.0,162.9,129.8,
129.7,129.2,124.4,114.2,55.4,53.2,52.7,25.1,21.5；ESI-HRMS m/z calcd for
C17H18N2O6S+Na+ 401.0787,found 401.0784.
Product I -3 is yellow solid, yield 86%；Fusing point: 151.7-152.5 DEG C of1H NMR(400MHz,CDCl3)δ
7.83 (d, J=8.4Hz, 2H), 7.30 (d, J=7.6Hz, 2H), 4.28 (s, 2H), 3.77 (s, 3H), 3.75 (s, 3H), 2.43
(s,3H),2.13(s,3H)；13C NMR(100MHz,CDCl3)δ171.1,170.8,163.9,162.9,143.0,129.8,
129.7,129.6,129.6,127.4,53.2,52.7,25.3,21.6,21.4.ESI-HRMS m/z calcd for
C17H18N2O5S+Na+ 385.0829,found 385.0831.
Product I -4 is yellow solid, yield 81%；Fusing point: 206.7-207.4 DEG C of1H NMR(400MHz,CDCl3)δ
8.35 (d, J=8.8Hz, 2H), 8.08 (d, J=9.2Hz, 2H), 4.26 (s, 2H), 3.79 (s, 6H), 2.20 (s, 3H)13C
NMR(100MHz,d6-DMSO)δ171.2,170.0,164.1,162.6,149.6,138.6,130.8,129.2,128.5,
124.0,53.6,52.8,25.2,21.6；ESI-HRMS m/z calcd for C16H15N3O7S+Na+ 416.0523,found
416.0526.
Product I -5 is yellow solid, yield 97%；Fusing point: 194.1-194.7 DEG C of1H NMR(400MHz,CDCl3)δ
8.02 (d, J=8.4Hz, 2H), 7.78 (d, J=8.8Hz, 2H), 4.25 (s, 2H), 3.76 (s, 3H), 3.75 (s, 3H), 2.15
(s,3H)；13C NMR(100MHz,CDCl3)δ171.1,168.0,163.8,162.6,137.1,132.6,130.7,129.9,
127.9,117.8,115.4,53.4,52.9,25.8,21.7；ESI-HRMS m/z calcd for C17H15N3O5S+Na+
396.0625,found 396.0629.
Product I -6 is yellow solid, yield 91%；Fusing point: 173.2-173.6 DEG C of1H NMR(400MHz,CDCl3)δ
8.03 (d, J=8.0Hz, 2H), 7.73 (d, J=8.4Hz, 2H), 4.28 (s, 2H), 3.75 (s, 6H), 2.14 (s, 3H)；13C
NMR(100MHz,CDCl3) δ 171.1,169.0,163.9,162.8,136.3,133.7 (q, J=32.7Hz), 130.4,
129.8,127.8,125.9 (q, J=3.7Hz), 123.5 (q, J=271.2Hz), 53.3,52.8,25.8,21.6；ESI-
HRMS m/z calcd for C17H15F3N2O5S+Na+ 439.0546,found 439.0548.
Product I -7 is yellow solid, yield 92%；Fusing point: 151.9-152.3 DEG C of1H NMR(400MHz,CDCl3)δ
7.96-7.90 (m, 2H), 7.15 (t, J=8.4Hz, 2H), 4.26 (s, 2H), 3.72 (s, 6H), 2.09 (s, 3H)；13C NMR
(100MHz,CDCl3) δ 170.8,170.1,165.2 (d, J=252.6Hz), 163.8 162.9,129.8,129.8 (d, J=
8.6Hz), 128.6,128.6,116.0 (d, J=21.8Hz), 53.2,52.7,25.4,21.5；ESI-HRMS m/z calcd
for C16H15FN2O5S+Na+ 389.0578,found 389.0574.
Product I -8 is yellow solid, yield 82%；Fusing point: 155.7-158.3 DEG C of1H NMR(400MHz,CDCl3)δ
7.85 (d, J=8.4Hz, 2H), 7.44 (d, J=8.8Hz, 2H), 4.25 (s, 2H), 3.74 (s, 6H), 2.10 (s, 3H)；13C
NMR(100MHz,CDCl3)δ170.9,169.8,163.9,162.8,138.6,131.0,130.0,129.8,129.2,
128.7,53.3,52.8,25.4,21.6；ESI-HRMS m/z calcd for C16H15ClN2O5S+Na+ 405.0282,
found 405.0281.
Product I -9 is yellow solid, yield 83%；Fusing point: 144.8-145.2 DEG C of1H NMR(400MHz,CDCl3)δ
7.78 (d, J=8.8Hz, 2H), 7.60 (d, J=8.4Hz, 2H), 4.24 (s, 2H), 3.74 (s, 6H), 2.11 (s, 3H)；13C
NMR(100MHz,CDCl3)δ170.9,169.9,163.8,162.8,132.2,131.5,130.0,129.7,128.9,
127.1,53.3,52.8,25.4,21.6；ESI-HRMS m/z calcd for C16H15BrN2O5S+Na+ 448.9777,
found 448.9778.
Product I -10 is yellow solid, yield 79%；Fusing point: 222.1-222.7 DEG C of1H NMR(400MHz,CDCl3)δ
8.30 (d, J=0.8Hz, 1H), 8.10 (dd, J=8.8,2.0Hz, 1H), 7.92 (d, J=8.4Hz, 2H), 7.89 (d, J=
8.0Hz,1H),7.63-7.54(m,2H),4.40(s,2H),3.79(s,3H),3.76(s,3H),2.18(s,3H)；13C NMR
(100MHz,CDCl3)δ171.0,170.9,164.0,163.0,135.0,132.6,130.0,129.9,129.8,128.9,
128.9,128.7,128.2,127.8,127.0,123.3,53.3,52.8,25.5,21.7；ESI-HRMS m/z calcd
for C20H18N2O5S+Na+ 421.0829,found 421.0828.
Product I -11 is yellow solid, yield 55%；Fusing point: 134.6-135.1 DEG C of1H NMR(400MHz,CDCl3)δ
7.67 (d, J=1.2Hz, 1H), 7.26 (d, J=3.6Hz, 1H), 6.63 (dd, J=3.6,1.6Hz, 1H), 4.23 (s, 2H),
3.77(s,6H),2.13(s,3H)；13C NMR(75MHz,CDCl3)δ171.1,164.0,162.8,161.8,146.9,
146.6,130.7,129.8,115.8,112.9,53.3,52.8,24.8,21.6；ESI-HRMS m/z calcd for
C14H14N2O6S+Na+ 361.0465,found 361.0464.
Product I -12 is yellow solid, yield 91%；Fusing point: 186.8-187.4 DEG C of1H NMR(400MHz,CDCl3)δ
3.85(s,2H),3.74(s,3H),3.72(s,3H),1.97(s,3H),1.29(s,9H)；13C NMR(100MHz,CDCl3)δ
182.6,170.3,163.9,162.9,129.5,129.1,53.2,52.6,39.2,27.6,23.9,21.4；ESI-HRMS m/
z calcd for C14H20N2O5S+Na+ 351.0985,found 351.0984.
Product I -13 is yellow solid, yield 64%；Fusing point: 212.3-212.5 DEG C of1H NMR(400MHz,CDCl3)δ
7.59-7.53 (m, 2H), 7.46-7.39 (m, 3H), 7.30 (d, J=16.4Hz, 1H), 7.00 (d, J=16.4Hz, 1H),
4.13(s,2H),3.77(s,6H),2.11(s,3H)；13C NMR(75MHz,CDCl3)δ171.0,170.9,164.0,162.9,
141.1,134.5,130.6,130.3,129.8,129.0,127.8,122.4,53.3,52.8,23.8,21.6；ESI-HRMS
m/z calcd for C18H18N2O5S+Na+ 397.0829,found 397.0827.
Product I -14 is yellow solid, yield 89%；Fusing point: 150.2-150.9 DEG C of1H NMR(400MHz,CDCl3)δ
7.91 (d, J=7.2Hz, 2H), 7.54 (t, J=7.2Hz, 1H), 7.47 (t, J=7.6Hz, 2H), 4.25 (s, 2H), 4.23-
4.14 (m, 4H), 2.11 (s, 3H), 1.27 (t, J=7.2Hz, 3H), 1.24 (t, J=6.8Hz, 3H)；13C NMR(100MHz,
CDCl3)δ170.9,170.8,163.5,162.3,132.7,132.2,130.0,129.9,128.8,127.4,62.5,61.9,
25.5,21.6,13.8,13.7；ESI-HRMS m/z calcd for C18H20N2O5S+H+ 377.1166,found
377.1164.
Product I -15 is yellow solid, yield 93%；Fusing point: 135.3-136.7 DEG C of1H NMR(400MHz,CDCl3)δ
7.88 (d, J=8.0Hz, 2H), 7.52-7.45 (m, 1H), 7.44-7.46 (m, 2H), 3.75 (s, 3H), 3.72 (s, 3H),
1.46(s,9H),(2H missing)；13C NMR(100MHz,CDCl3)δ171.2,164.0,163.1,151.4,133.0,
131.8,128.6,127.6,83.0,53.2,52.5,28.0,26.1,(2C missing)；ESI-HRMS m/z calcd
for C19H22N2O6S+Na+ 429.1091,found 429.1089.
Product I -16 is yellow solid, yield 67%；Fusing point: 57-58 DEG C of1H NMR(400MHz,CDCl3)δ7.86
(d, J=8.8Hz, 2H), 6.92 (d, J=9.2Hz, 2H), 3.83 (s, 3H), 3.77 (s, 3H), 3.73 (s, 3H), 1.47 (s,
9H),(2H missing)；13C NMR(100MHz,CDCl3)δ170.7,164.2,163.2,162.7,129.5,125.2,
114.1,83.0,55.4,53.2,52.5,28.1,26.0,(3C missing)；ESI-HRMS m/z calcd for
C20H24N2O7S+H+ 437.1377,found 437.1371.
Product I -17 is yellow solid, yield 83%；Fusing point: 62-63 DEG C of1H NMR(400MHz,CDCl3)δ7.78
(d, J=8.4Hz, 2H), 7.22 (d, J=8.0Hz, 2H), 3.76 (s, 3H), 3.72 (s, 3H), 2.37 (s, 3H), 1.46 (s,
9H),(2H missing)；13C NMR(100MHz,CDCl3)δ171.1,164.1,163.1,151.4,142.4,130.1,
129.3,127.6,82.9,53.1,52.4,28.0,26.0,21.3,(2C missing)；ESI-HRMS m/z calcd for
C20H24N2O6S+H+ 421.1428,found 421.1427.
Product I -18 is yellow solid, yield 97%；Fusing point: 74-75 DEG C of1H NMR(400MHz,CDCl3)δ8.22
(d, J=8.8Hz, 2H), 8.06 (d, J=8.8Hz, 2H), 3.74 (s, 3H), 3.71 (s, 3H), 1.44 (s, 9H), (2H
missing)；13C NMR(100MHz,CDCl3)δ169.1,163.8,162.9,151.2,149.5,139.0,130.8,
128.8,128.6,123.7,83.5,53.2,52.6,27.9,26.0；ESI-HRMS m/z calcd for C19H21N3O8S+
Na+ 474.0942,found 474.0941.
Product I -19 is yellow solid, yield 95%；Fusing point: 64-65 DEG C of1H NMR(400MHz,CDCl3)δ8.02
(d, J=8.0Hz, 2H), 7.68 (d, J=8.0Hz, 2H), 3.77 (s, 3H), 3.74 (s, 3H), 1.47 (s, 9H), (2H
missing)；13C NMR(100MHz,CDCl3) δ 169.9,164.0,163.0,151.4,136.6,133.3 (q, J=
32.6Hz), 131.0,128.8,128.0,125.6 (q, J=3.7Hz), 123.6 (q, J=270.9Hz), 83.4,53.3,
52.6,28.0,26.2；ESI-HRMS m/z calcd for C20H21F3N2O6S+Na+ 497.0965,found 497.0966.
Product I -20 is yellow solid, yield 92%；Fusing point: 74-75 DEG C of1H NMR(400MHz,CDCl3)δ7.92–
7.82(m,2H),7.10–6.99(m,4H),3.72(s,3H),3.68(s,3H),1.42(s,9H),(2H missing)；13C
NMR(100MHz,CDCl3) δ 170.1,164.8 (d, J=251.6Hz), 163.9,163.0,151.3,130.9,129.8 (d, J
=8.8Hz), 129.0 (d, J=2.5Hz), 128.4,115.67 (d, J=21.8Hz), 83.0,53.1,52.4,27.8,
25.9；ESI-HRMS m/z calcd for C19H21FN2O6S+Na+ 447.0997,found 447.0995.
Product I -21 is yellow solid, yield 84%；Fusing point: 144-145 DEG C of1H NMR(400MHz,CDCl3)δ7.59
(d, J=1.2Hz, 1H), 7.22 (d, J=3.2Hz, 1H), 6.54 (dd, J=3.6,1.6Hz, 1H), 3.74 (s, 3H), 3.72
(s,3H),1.44(s,9H),(2H missing)；13C NMR(100MHz,CDCl3)δ164.0,162.9,162.0,151.5,
147.0,146.0,131.9,128.2,115.4,112.6,83.0,53.2,52.4,27.9,25.0；ESI-HRMS m/z
calcd for C17H20N2O7S+Na+ 419.0883,found 419.0885.
Product I -22 is yellow solid, yield 51%；Fusing point: 130-131 DEG C of1H NMR(400MHz,CDCl3)δ3.74
(s,3H),3.73(s,3H),1.41(s,9H),1.28(s,9H),(2H missing)；13C NMR(100MHz,CDCl3)δ
182.2,164.1,163.1,151.0,82.5,53.2,52.4,39.0,28.0,27.8,24.4,(2C missing)；ESI-
HRMS m/z calcd for C17H26N2O6S+Na+ 409.1404,found 409.1403.
Product I -23 is yellow solid, yield 52%；Fusing point: 88-89 DEG C of1H NMR(400MHz,CDCl3)δ7.50–
7.46 (m, 2H), 7.40-7.31 (m, 3H), 7.21 (d, J=16.4Hz, 1H), 7.01 (d, J=16.4Hz, 1H), 3.75 (s,
3H),3.72(s,3H),1.45(s,9H),(2H missing)；13C NMR(100MHz,CDCl3)δ170.7,164.1,
163.0,151.6,140.3,134.7,131.8,129.8,128.8,128.6,127.5,122.8,83.0,53.2,52.4,
27.9,24.1；ESI-HRMS m/z calcd for C21H24N2O6S+Na+ 455.1247,found 455.1248.
Product I -24 is yellow solid, yield 96%；Fusing point: 56-57 DEG C of1H NMR(400MHz,CDCl3)δ7.88
(d, J=7.6Hz, 2H), 7.47 (t, J=7.6Hz, 1H), 7.40 (t, J=7.6Hz, 2H), 4.22-4.12 (m, 4H), 1.46
(s, 9H), 1.27 (t, J=7.2Hz, 3H), 1.22 (t, J=7.2Hz, 3H), (2H missing)；13C NMR(100MHz,
CDCl3)δ171.2,163.6,162.6,151.3,133.1,131.6,128.5,127.5,82.8,62.4,61.7,28.0,
26.0,13.8,13.6,(2C missing)；ESI-HRMS m/z calcd for C21H26N2O6S+Na+ 457.1404,
found 457.1407.
Product II -2 is white solid, yield 79%；Fusing point: 128.0-129.0 DEG C of1H NMR(400MHz,d6-
DMSO) δ 7.97 (d, J=9.2Hz, 2H), 7.06 (d, J=8.8Hz, 2H), 5.04 (d, J=14.0Hz, 1H), 4.63 (d, J=
14.0Hz,1H),3.84(s,3H),3.74(s,3H),3.72(s,3H),2.22(s,3H)；13C NMR(100MHz,d6-DMSO)
δ171.3,170.5,164.1,162.8,162.7,140.3,130.4,127.2,125.9,114.1,55.6,53.6,53.4,
46.7,22.0；ESI-HRMS m/z calcd for C17H18N2O7S+Na+ 417.0727,found 417.0726.
Product II -3 is white solid, yield 78%；Fusing point: 96.0-97.0 DEG C of1H NMR(400MHz,CDCl3)δ
7.80 (d, J=8.0Hz, 2H), 7.28 (d, J=8.0Hz, 2H), 4.46 (d, J=13.2Hz, 1H), 4.27 (d, J=
13.2Hz,1H),3.84(s,6H),2.41(s,3H),2.36(s,3H)；13C NMR(100MHz,CDCl3)δ172.4,166.1,
163.1,162.4,143.4,140.6,131.6,129.7,127.8,127.2,53.5,47.8,22.3,21.5,(1C
missing)；ESI-HRMS m/z calcd for C17H18N2O6S+Na+ 401.0778,found 401.0780.
Product II -4 is white solid, yield 85%；Fusing point: 139.0-139.7 DEG C of1H NMR(400MHz,CDCl3)δ
8.02 (d, J=8.4Hz, 2H), 7.74 (d, J=8.4Hz, 2H), 4.52 (d, J=13.6Hz, 1H), 4.30 (d, J=
13.6Hz,1H),3.85(s,3H),3.84(s,3H),2.38(s,3H)；13C NMR(100MHz,CDCl3)δ172.3,165.3,
(162.7,162.1,139.8,137.8,133.8 q, J=32.7Hz), 128.8,128.3,125.9 (q, J=3.7Hz),
123.5 (q, J=271.0Hz), 53.6,48.1,22.2, (1C missing)；ESI-HRMS m/z calcd for
C17H15F3N2O6S+Na+ 455.0495,found 455.0486.
Product II -5 is white solid, yield 78%；Fusing point: 26.2-127.1 DEG C of1H NMR(400MHz,CDCl3)δ
7.97-7.89 (m, 2H), 7.20-7.13 (m, 2H), 4.48 (d, J=13.6Hz, 1H), 4.27 (d, J=13.6Hz, 1H),
3.84(s,3H),3.83(s,3H),2.35(s,3H)；13C NMR(100MHz,d6-DMSO)δ171.2,170.6,164.6(d,J
=249.6Hz), 164.0,162.7,139.9,131.4 (d, J=2.9Hz), 131.2 (d, J=9.1Hz), 126.1,115.8
(d, J=21.8Hz), 53.6,53.4,47.1,22.1；ESI-HRMS m/z calcd for C16H15FN2O6S+Na+
405.0527,found 405.0522.
Product II -6 is white solid, yield 72%；Fusing point: 72.0-73.0 DEG C of1H NMR(400MHz,d6-DMSO)δ
7.96-7.92 (m, 2H), 7.61-7.56 (m, 1H), 7.54-7.49 (m, 2H), 5.01 (d, J=14.0Hz, 1H), 4.76 (d, J
=14.0Hz, 1H), 3.79 (s, 3H), 3.75 (s, 3H), 1.45 (s, 9H)；13C NMR(100MHz,d6-DMSO)δ170.9,
164.1,163.1,149.7,140.0,134.8,132.1,128.7,128.3,126.0,84.8,53.6,47.2,27.5,(1C
missing)；ESI-HRMS m/z calcd for C19H22N2O7S+Na+ 445.1040,found 445.1039.
Product II -7 is white solid, yield 69%；Fusing point: 75-76 DEG C of1H NMR(400MHz,d6-DMSO)δ7.90
(d, J=8.8Hz, 2H), 7.05 (d, J=8.8Hz, 2H), 4.95 (d, J=14.0Hz, 1H), 4.66 (d, J=13.6Hz,
1H),3.83(s,3H),3.78(s,3H),3.74(s,3H),1.44(s,9H)；13C NMR(100MHz,d6-DMSO)δ169.9,
164.1,163.1,162.5,149.8,140.5,130.2,127.3,125.6,114.1,84.6,55.6,54.9,53.5,
46.9,27.5；ESI-HRMS m/z calcd for C20H24N2O8S+Na+ 475.1146,found 475.1148.
Product II -8 is white solid, yield 62%；Fusing point: 69-70 DEG C of1H NMR(400MHz,d6-DMSO)δ7.84
(d, J=8.4Hz, 2H), 7.31 (d, J=8.0Hz, 2H), 4.94 (d, J=14.0Hz, 1H), 4.68 (d, J=14.0Hz,
1H),3.80(s,3H),3.75(s,3H),2.36(s,3H),1.45(s,9H)；13C NMR(100MHz,d6-DMSO)δ170.5,
164.1,163.1,149.7,142.4,140.2,132.2,129.2,128.2,125.9,84.7,53.5(2C),47.1,
27.5,21.0；ESI-HRMS m/z calcd for C20H24N2O7S+Na+ 459.1196,found 459.1197.
Product II -9 is white solid, yield 67%；Fusing point: 78-79 DEG C of1H NMR(400MHz,d6-DMSO)δ8.13
(d, J=8.4Hz, 2H), 7.87 (d, J=8.4Hz, 2H), 5.05 (d, J=14.0Hz, 1H), 4.79 (d, J=14.0Hz,
1H),3.80(s,3H),3.75(s,3H),1.45(s,9H)；13C NMR(100MHz,d6-DMSO)δ170.1,164.0,
(163.0,149.7,139.8,138.7,131.8 q, J=31.9Hz), 129.1,126.6,125.6 (q, J=3.6Hz),
123.9 (q, J=270.8Hz), 85.2,53.7,47.5,27.5, (1C missing)；ESI-HRMS m/z calcd for
C20H21F3N2O7S+Na+ 513.0914,found 513.0915.
Product II -10 is white solid, yield 72%；Fusing point: 67-68 DEG C of1H NMR(400MHz,d6-DMSO)δ
8.00 (dd, J=8.8,5.6Hz, 2H), 7.34 (dd, J=8.8,8.8Hz, 2H), 4.99 (d, J=13.6Hz, 1H), 4.73
(d, J=14.0Hz, 1H), 3.80 (s, 3H), 3.75 (s, 3H), 1.45 (s, 9H)；13C NMR(100MHz,d6-DMSO)δ
170.0,164.5 (d, J=249.6Hz), 164.0,163.0,149.7,140.1,131.5 (d, J=2.9Hz), 131.0 (d, J
=9.0Hz), 126.0,115.8 (d, J=21.8Hz), 84.9,53.6,47.2,27.5, (1C missing)；ESI-HRMS
m/z calcd for C19H21FN2O7S+Na+ 463.0946,found 463.0949.
Product II -11 is white solid, yield 73%；Fusing point: 72-73 DEG C of1H NMR(400MHz,d6-DMSO)δ
8.32 (d, J=9.2Hz, 2H), 8.17 (d, J=8.8Hz, 2H), 5.07 (d, J=14.0Hz, 1H), 4.82 (d, J=
14.0Hz,1H),3.81(s,3H),3.77(s,3H),1.46(s,9H)；13C NMR(100MHz,d6-DMSO)δ169.6,
163.9,162.9,149.6,149.3,140.5,139.5,129.6,126.9,123.7,85.2,53.6(2C),47.6,
27.5；ESI-HRMS m/z calcd for C19H21N3O9S+Na+ 490.0891,found 490.0892.
Product II -12 is white solid, yield 78%；Fusing point: 77-78 DEG C of1H NMR(400MHz,d6-DMSO)δ
7.98 (d, J=0.8Hz, 1H), 7.41 (d, J=3.6Hz, 1H), 6.72 (dd, J=3.2,1.6Hz, 1H), 4.76 (d, J=
14.0Hz, 1H), 4.69 (d, J=13.6Hz, 1H), 3.78 (s, 3H), 3.74 (s, 3H), 1.43 (s, 9H)；13C NMR
(100MHz,d6-DMSO)δ164.1,163.1,160.0,149.8,149.2,147.8,140.5,126.3,119.8,113.0,
84.9,53.6,47.0,27.5,(1C missing)；ESI-HRMS m/z calcd for C17H20N2O8S+Na+
435.0833,found 435.0832.
Product II -13 is white solid, yield 78%；Fusing point: 58-59 DEG C of1H NMR(400MHz,d6-DMSO)δ
4.46 (d, J=13.2Hz, 1H), 4.37 (d, J=13.6Hz, 1H), 3.76 (s, 3H), 3.74 (s, 3H), 1.41 (s, 9H),
1.16(s,9H)；13C NMR(100MHz,d6-DMSO)δ180.2,164.0,163.0,149.5,140.0,124.7,84.4,
53.4,46.6,38.5,27.5,27.1,(1C missing)；ESI-HRMS m/z calcd for C17H26N2O7S+Na+
425.1353,found 425.1354.
Product II -14 is white solid, yield 74%；Fusing point: 87-88 DEG C of1H NMR(400MHz,d6-DMSO)δ
7.67 (d, J=6.4Hz, 2H), 7.56 (d, J=16.4Hz, 1H), 7.47-7.40 (m, 3H), 7.15 (d, J=16.4Hz,
1H), 4.84 (d, J=13.6Hz, 1H), 4.57 (d, J=14.0Hz, 1H), 3.78 (s, 3H), 3.74 (s, 3H), 1.43 (s,
9H)；13C NMR(100MHz,d6-DMSO)δ170.1,164.1,163.1,149.9,143.2,140.2,135.1,130.3,
129.1,128.1,126.7,125.6,84.9,53.6,45.7,27.6,(1C missing)；ESI-HRMS m/z calcd
for C21H24N2O7S+Na+ 471.1196,found 471.1196.
Product II -15 is white solid, yield 69%；Fusing point: 62-63 DEG C of1H NMR(400MHz,d6-DMSO)δ
7.94 (d, J=7.2Hz, 2H), 7.58 (t, J=7.2Hz, 1H), 7.51 (t, J=7.2Hz, 2H), 4.96 (d, J=14.0Hz,
1H), 4.71 (d, J=14.0Hz, 1H), 4.32-4.12 (m, 4H), 1.46 (s, 9H), 1.26 (t, J=7.2Hz, 3H), 1.20
(t, J=7.2Hz, 3H)；13C NMR(100MHz,d6-DMSO)δ170.9,163.6,162.4,149.9,140.0,134.9,
132.1,128.7,128.3,126.6,84.7,62.8,62.6,47.3,27.6,13.7,13.6；ESI-HRMS m/z calcd
for C21H26N2O7S+Na+ 473.1353,found 473.1353.
Product III -2 is white solid, yield 69%；Fusing point: 199.3-199.6 DEG C of1H NMR(400MHz,CDCl3)δ
7.95 (d, J=8.8Hz, 2H), 7.00 (d, J=9.2Hz, 2H), 4.70 (s, 2H), 3.89 (s, 3H), 3.85 (s, 3H), 3.84
(s,3H),2.33(s,3H)；13C NMR(100MHz,CDCl3)δ172.7,163.7,162.5,161.9,160.5,143.0,
130.3,126.1,124.0,114.6,55.6,54.2,53.7,53.7,22.4；ESI-HRMS m/z calcd for
C17H18N2O8S+H+ 433.0676,found 433.0669.
Product III -3 is white solid, yield 72%；Fusing point: 212.2-212.6 DEG C of1H NMR(400MHz,CDCl3)δ
7.88 (d, J=8.4Hz, 2H), 7.32 (d, J=8.0Hz, 2H), 4.72 (s, 2H), 3.86 (s, 3H), 3.84 (s, 3H), 2.44
(s,3H),2.34(s,3H)；13C NMR(100MHz,d6-DMSO)δ172.2,164.9,161.8,160.3,143.6,140.9,
129.6,129.2,128.7,126.6,54.1,53.8,53.7,22.0,21.1；ESI-HRMS m/z calcd for
C17H18N2O7S+Na+ 417.0727,found 417.0722.
Product III -4 is white solid, yield 66%；Fusing point: 130.0-131.0 DEG C of1H NMR(400MHz,CDCl3)δ
8.11 (d, J=8.4Hz, 2H), 7.80 (d, J=8.4Hz, 2H), 4.76 (s, 2H), 3.88 (s, 3H), 3.85 (s, 3H), 2.37
(s,3H)；13C NMR(100MHz,CDCl3) δ 172.5,161.8,161.7,160.2,142.3,135.1,134.4 (q, J=
33.0Hz), 128.7,126.6,126.1 (q, J=3.4Hz), 124.8 (q, J=271.2Hz), 54.5,53.9,53.9,
22.4；ESI-HRMS m/z calcd for C17H15F3N2O7S+Na+ 471.0444,found 471.0438.
Product III -5 is white solid, yield 62%；Fusing point: 189.1-189.6 DEG C of1H NMR(400MHz,CDCl3)δ
8.05-7.99(m,2H),7.25-7.18(m,2H),4.72(s,2H),3.86(s,3H),3.84(s,3H),2.34(s,3H)；13C NMR(100MHz,d6- DMSO) δ 172.2,165.0 (d, J=250.9Hz), 164.2,161.8,160.2,140.8,
131.5 (d, J=9.3Hz), 128.5 (d, J=2.9Hz), 126.6,116.2 (d, J=21.9Hz), 54.2,53.8,53.7,
22.1；ESI-HRMS m/z calcd for C16H15FN2O7S+Na+ 421.0476,found 421.0473.
Product III -6 is white solid, yield 70%；Fusing point: 80.2-80.9 DEG C of1H NMR(400MHz,CDCl3)δ
7.98 (d, J=7.2Hz, 2H), 7.56 (t, J=7.2Hz, 1H), 7.47 (t, J=7.2Hz, 2H), 4.76 (s, 2H), 3.86
(s,3H),3.84(s,3H),1.52(s,9H)；13C NMR(100MHz,CDCl3)δ163.9,162.1,160.4,150.1,
142.7,132.7,132.1,128.9,128.4,125.5,86.5,55.1,53.7,53.6,27.7；ESI-HRMS m/z
calcd for C19H22N2O8S+Na+ 461.0989,found 461.0985.
Product III -7 is white solid, yield 69%；Fusing point: 153-154 DEG C of1H NMR(400MHz,(CD3)2CO)δ
7.95 (s, 1H), 7.59 (d, J=3.6Hz, 1H), 6.78 (dd, J=3.6,1.6Hz, 1H), 5.16 (s, 2H), 3.86 (s,
3H),3.79(s,3H),1.48(s,9H)；13C NMR(100MHz,(CD3)2CO)δ163.3,161.4,155.9,151.1,
149.1,148.3,142.8,128.3,120.1,113.9,86.1,55.2,54.1,53.9,28.0；ESI-HRMS m/z
calcd for C17H20N2O9S+Na+ 451.0782,found 451.0781.
Product III -8 is white solid, yield 71%；Fusing point: 136-137 DEG C of1H NMR(400MHz,CDCl3)δ
7.57-7.53 (m, 2H), 7.45-7.38 (m, 4H), 7.11 (d, J=16.4Hz, 1H), 4.62 (s, 2H), 3.86 (s, 3H),
3.85(s,3H),1.52(s,9H)；13C NMR(100MHz,CDCl3)δ163.7,162.1,160.4,150.2,143.8,
142.9,134.4,130.6,129.0,128.2,128.1,126.5,122.4,86.6,53.8,53.7,27.8；ESI-HRMS
m/z calcd for C21H24N2O8S+Na+ 487.1146,found 487.1144.
Product III -9 is white solid, yield 68%；Fusing point: 78-79 DEG C of1H NMR(400MHz,CDCl3)δ4.34
(s,2H),3.85(s,3H),3.84(s,3H),1.47(s,9H),1.30(s,9H)；13C NMR(100MHz,CDCl3)δ
174.7,162.1,160.5,150.0,141.8,125.6,85.9,54.3,53.7,53.5,39.4,27.8,27.7；ESI-
HRMS m/z calcd for C17H26N2O8S+Na+ 441.1302,found 441.1299.
Finally, it should be noted that the foregoing is only a preferred embodiment of the present invention, it is not intended to restrict the invention,
Although the present invention is described in detail referring to the foregoing embodiments, for those skilled in the art, still may be used
To modify the technical solutions described in the foregoing embodiments or equivalent replacement of some of the technical features.
It is all within the contents of the present invention and principle, any modification, equivalent replacement, improvement and so on should be included in of the invention
Within protection scope.
Claims (8)
1.2,5- dihydros-Isosorbide-5-Nitrae, 5- sulphur phenodiazine Zhuo and its oxide, which is characterized in that structure 2,5- bis- as shown in I in formula 1
Hydrogen -1,4,5- sulphur phenodiazine Zhuo, II and III are the oxidation product of 2,5- dihydro -1,4,5- sulphur phenodiazine Zhuo.
Wherein: R1For substituted aryl substituent group, (replace on phenyl ring includes 4- methoxyl group, 4- methyl, 4- nitro, 4- cyano, 4- trifluoro
Methyl, 4- fluorine, 4- chlorine, 4- bromine) 1- naphthyl substituted base, 2- furyl substituent, alkyl substituent, alkenyl group；R2For acetyl
Base or tertbutyloxycarbonyl substituent group；R3For methyl substituents or ethyl substituent.
2. 2,5- dihydro-Isosorbide-5-Nitrae according to claim 1,5- sulphur phenodiazine Zhuo and its oxide, which is characterized in that in formula 1
Shown in I, heptatomic ring contain there are three it is heteroatomic simultaneously, also containing there are four different types of substituent group, and the analog derivative can be with
The product II and III of different oxidation state is obtained by the oxidation of controllability.
3. 2,5- dihydro-Isosorbide-5-Nitrae described in claim 1,5- sulphur phenodiazine Zhuo and its oxide, which is characterized in that preparation method is such as
Shown in formula 2:
The preparation method of target compound I: compound shown in compound shown in general formulae IV, general formula V and powdered sodium carbonate are existed
It is dissolved in dichloromethane solvent under room temperature, reactant IV disappears completely, has removing under reaction mixture reduced pressure
Solvent, column chromatographic elution obtain target compound I, and X is bromine or chlorine.
4. 2,5- dihydro-Isosorbide-5-Nitrae described in claim 1,5- sulphur phenodiazine Zhuo and its oxide, which is characterized in that target compound
II preparation method: i.e. by m-CPBA, that is, metachloroperbenzoic acid of compound shown in general formula I and appropriate equivalent, in room temperature condition
Under be dissolved in dichloromethane solvent, reactant I disappears completely, and organic solvent, column will be removed under reaction mixture reduced pressure
Chromatographic elution obtains target compound II.
5. 2,5- dihydro-Isosorbide-5-Nitrae described in claim 1,5- sulphur phenodiazine Zhuo and its oxide, which is characterized in that target compound
III preparation method: compound shown in general formula I and appropriate excessive m-CPBA are dissolved in methylene chloride at room temperature
In solvent, reactant I disappears completely, and organic solvent will be removed under reaction mixture reduced pressure, and column chromatographic elution obtains target
Compound III.
6. according to the dihydro of 2,5- described in claim 3-5-Isosorbide-5-Nitrae, the preparation method of 5- sulphur phenodiazine Zhuo and its oxide, feature
It is the alkali for using inorganic reagent sodium carbonate as reaction, using methylene chloride as reaction dissolvent, reacts under room temperature
Obtain target compound I；Use m-CPBA as oxidant, using methylene chloride as reaction dissolvent, is aoxidized only by control
The addition equivalent of agent, reaction can respectively obtain the target compound II and III of different oxidation state under room temperature.
7. according to the dihydro of 2,5- described in claim 3-5-Isosorbide-5-Nitrae, the preparation method of 5- sulphur phenodiazine Zhuo and its oxide, feature
The molar ratio for being compounds Ⅳ, compound V and carbonate reagent is IV: V: sodium carbonate=1.0:1.5:2.0, methylene chloride
Solution concentration is 0.1M, i.e., 0.1 mole every liter can be obtained target compound I；Chemical compounds I, m-CPBA molar ratio be I: m-
CPBA=1.0:1.0, dichloromethane solution concentration are that target compound II can be obtained in 0.15M；Chemical compounds I, m-CPBA rub
, than being I: m-CPBA=1.0:3.0, dichloromethane solution concentration is that target compound III can be obtained in 0.15M for you.
8. according to the dihydro of 2,5- described in claim 3-5-Isosorbide-5-Nitrae, the preparation method of 5- sulphur phenodiazine Zhuo and its oxide, feature
It is that eluent used in silica gel column chromatography is the mixed solvent of petroleum ether and ethyl acetate, and volume ratio VPetroleum ether:VEthyl acetate=5:
Target compound I can be obtained in 1~2:1；Eluent used in silica gel column chromatography is the mixed solvent of petroleum ether and ethyl acetate,
And volume ratio VPetroleum ether:VEthyl acetateTarget compound II can be obtained in=3:1~1:1；Eluent used in silica gel column chromatography is petroleum
The mixed solvent of ether and ethyl acetate, and volume ratio VPetroleum ether:VEthyl acetateTarget compound III can be obtained in=10:1~3:1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910258698.XA CN110041290A (en) | 2019-04-01 | 2019-04-01 | 2,5- dihydro -1,4,5- sulphur phenodiazine Zhuo and its oxide preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910258698.XA CN110041290A (en) | 2019-04-01 | 2019-04-01 | 2,5- dihydro -1,4,5- sulphur phenodiazine Zhuo and its oxide preparation method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110041290A true CN110041290A (en) | 2019-07-23 |
Family
ID=67275783
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910258698.XA Pending CN110041290A (en) | 2019-04-01 | 2019-04-01 | 2,5- dihydro -1,4,5- sulphur phenodiazine Zhuo and its oxide preparation method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110041290A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111484476A (en) * | 2020-04-13 | 2020-08-04 | 深圳职业技术学院 | 3-hydro-1, 2-dithio-2, 2-dioxide and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2017160139A (en) * | 2016-03-08 | 2017-09-14 | 国立大学法人名古屋大学 | Production method for bi(hetero)aryl(thio)ether compound |
| CN110156815A (en) * | 2019-06-04 | 2019-08-23 | 兰州大学 | 12a hydrogen-benzo [f] pyridine [1,2-d] [1,4] sulphur nitrogen Zhuo and preparation method thereof |
-
2019
- 2019-04-01 CN CN201910258698.XA patent/CN110041290A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2017160139A (en) * | 2016-03-08 | 2017-09-14 | 国立大学法人名古屋大学 | Production method for bi(hetero)aryl(thio)ether compound |
| CN110156815A (en) * | 2019-06-04 | 2019-08-23 | 兰州大学 | 12a hydrogen-benzo [f] pyridine [1,2-d] [1,4] sulphur nitrogen Zhuo and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| BIN CHENG等: "Pyridinium 1,4-zwitterionix thiolates as a useful class of sulfur-containing synthons:application to the synthesis of 2,5-dihydro-1,4,5-thiadiazepines", 《CHEMCOMM》 * |
| BIN CHENG等: "Switchable Ring-Contractive Extrusion Reactions of 2，5-Dihydro-1,4,5-thiadiazepine S-Oxides:Entries to Pyridazines or Pyrazoles", 《THE JOURNAL OF ORGANIC CHEMISTRY》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111484476A (en) * | 2020-04-13 | 2020-08-04 | 深圳职业技术学院 | 3-hydro-1, 2-dithio-2, 2-dioxide and preparation method thereof |
| CN111484476B (en) * | 2020-04-13 | 2021-06-22 | 深圳职业技术学院 | 3-hydro-1, 2-dithio-2, 2-dioxide and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106608788B (en) | A kind of preparation method of mild diazomethane derivative | |
| CN110240568A (en) | Three replace pyridazine analog derivative and preparation method thereof | |
| CN106928201A (en) | The method for synthesizing 2 vinyl indole derivativeses | |
| WO2022206010A1 (en) | Simple preparation method for isoxazolines | |
| CN109438264A (en) | A kind of polysubstituted indenes amine derivative and preparation method thereof | |
| CN110041290A (en) | 2,5- dihydro -1,4,5- sulphur phenodiazine Zhuo and its oxide preparation method | |
| CN107382820A (en) | A kind of synthetic method of 3 arylisoindole derivative | |
| Li et al. | Ag2CO3-catalyzed efficient synthesis of internal or terminal propargylicamines and chalcones via A3-coupling under solvent-free condition | |
| CN113234037B (en) | Z-2- (2-acylmethylene) thiazolidine-4-ketone derivative and preparation method and application thereof | |
| CN105218540B (en) | A kind of preparation method of 3 thiocarbamoyl imidazoles of C simultaneously [1,2 a] pyridine compounds and their | |
| CN106188044A (en) | A kind of synthetic method of 3 arylthio imidazos [1,5 a] the N heterocyclic compound of catalysis of iodine | |
| CN104326892A (en) | Synthetic method of indanone by gold-catalysis | |
| WO2019168874A1 (en) | Difluoromethoxylation and trifluoromethoxylation compositions and methods for synthesizing same | |
| CN110156815A (en) | 12a hydrogen-benzo [f] pyridine [1,2-d] [1,4] sulphur nitrogen Zhuo and preparation method thereof | |
| CN107739317A (en) | A kind of preparation method and applications of perfluoroalkyl diazomethane | |
| CN108610275A (en) | A kind of synthetic method of 3- (2- vinyls) indole derivatives | |
| CN110105285A (en) | Three substituted pyrazole derivatives and preparation method thereof | |
| JP2007238540A (en) | Method for producing optically active alcohol compound | |
| CN110028451A (en) | A kind of full substituted pyrazole derivative preparation method | |
| CN108218840A (en) | A kind of synthetic method of bisindole derivatives | |
| CN104016872B (en) | A kind of synthetic method of chiral alpha-non-natural amino acid | |
| CN110240572B (en) | Synthesis method of trans-1, 1-cyclopropane dicarboxylic acid ester | |
| CN106854191B (en) | 2- 3- methylene -2,3-dihydrofuran synthetic methods containing chiral quaternary carbon center | |
| CN107021968B (en) | The method of the polysubstituted organic photochemical catalyst catalyzing indole quinoline class compound oxidation dehydrogenation synthesis of indole class compound of BODIPY | |
| CN108368048A (en) | Five fluorine sulfenyl pyridines |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20190723 |
|
| RJ01 | Rejection of invention patent application after publication |