CN105753801B - A kind of preparation method of s-triazine compound - Google Patents
A kind of preparation method of s-triazine compound Download PDFInfo
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- CN105753801B CN105753801B CN201610177528.5A CN201610177528A CN105753801B CN 105753801 B CN105753801 B CN 105753801B CN 201610177528 A CN201610177528 A CN 201610177528A CN 105753801 B CN105753801 B CN 105753801B
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- 238000002360 preparation method Methods 0.000 title claims abstract description 42
- -1 s-triazine compound Chemical class 0.000 title claims abstract description 23
- 239000002904 solvent Substances 0.000 claims abstract description 14
- 239000003054 catalyst Substances 0.000 claims abstract description 7
- 229910052751 metal Inorganic materials 0.000 claims abstract description 7
- 239000002184 metal Substances 0.000 claims abstract description 7
- FKPUYTAEIPNGRM-UHFFFAOYSA-N 1-(diaminomethylidene)guanidine;hydron;chloride Chemical compound [Cl-].N\C([NH3+])=N/C(N)=N FKPUYTAEIPNGRM-UHFFFAOYSA-N 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims description 62
- 150000001805 chlorine compounds Chemical class 0.000 claims description 12
- VYXHVRARDIDEHS-UHFFFAOYSA-N 1,5-cyclooctadiene Chemical compound C1CC=CCCC=C1 VYXHVRARDIDEHS-UHFFFAOYSA-N 0.000 claims description 10
- 239000004912 1,5-cyclooctadiene Substances 0.000 claims description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 239000012141 concentrate Substances 0.000 claims description 5
- 239000003480 eluent Substances 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- COHUUWHPQXYAII-UHFFFAOYSA-N C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1=CC=CC1 Chemical compound C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1=CC=CC1 COHUUWHPQXYAII-UHFFFAOYSA-N 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 3
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 claims description 3
- JEYWNNAZDLFBFF-UHFFFAOYSA-N Nafoxidine Chemical group C1CC2=CC(OC)=CC=C2C(C=2C=CC(OCCN3CCCC3)=CC=2)=C1C1=CC=CC=C1 JEYWNNAZDLFBFF-UHFFFAOYSA-N 0.000 claims description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 3
- 238000004440 column chromatography Methods 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 239000012044 organic layer Substances 0.000 claims description 3
- YBCAZPLXEGKKFM-UHFFFAOYSA-K ruthenium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Ru+3] YBCAZPLXEGKKFM-UHFFFAOYSA-K 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- NHOWDZOIZKMVAI-UHFFFAOYSA-N (2-chlorophenyl)(4-chlorophenyl)pyrimidin-5-ylmethanol Chemical compound C=1N=CN=CC=1C(C=1C(=CC=CC=1)Cl)(O)C1=CC=C(Cl)C=C1 NHOWDZOIZKMVAI-UHFFFAOYSA-N 0.000 claims description 2
- ZPQOPVIELGIULI-UHFFFAOYSA-N 1,3-dichlorobenzene Chemical compound ClC1=CC=CC(Cl)=C1 ZPQOPVIELGIULI-UHFFFAOYSA-N 0.000 claims description 2
- 125000001617 2,3-dimethoxy phenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 2
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000001072 heteroaryl group Chemical group 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 238000000034 method Methods 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 238000012805 post-processing Methods 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- JIHQDMXYYFUGFV-UHFFFAOYSA-N 1,3,5-triazine Chemical compound C1=NC=NC=N1 JIHQDMXYYFUGFV-UHFFFAOYSA-N 0.000 claims 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 1
- 238000001914 filtration Methods 0.000 claims 1
- RPGWZZNNEUHDAQ-UHFFFAOYSA-N phenylphosphine Chemical compound PC1=CC=CC=C1 RPGWZZNNEUHDAQ-UHFFFAOYSA-N 0.000 claims 1
- 125000003944 tolyl group Chemical group 0.000 claims 1
- 239000002994 raw material Substances 0.000 abstract description 2
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 42
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 38
- 238000005160 1H NMR spectroscopy Methods 0.000 description 19
- 235000019445 benzyl alcohol Nutrition 0.000 description 15
- 229960004217 benzyl alcohol Drugs 0.000 description 14
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 8
- 229960003105 metformin Drugs 0.000 description 8
- 0 *NC(NC(N(*)*)=N)=N Chemical compound *NC(NC(N(*)*)=N)=N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 229910052707 ruthenium Inorganic materials 0.000 description 3
- 150000003918 triazines Chemical class 0.000 description 3
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- NTTLKRPWPKPUAI-UHFFFAOYSA-N (1e)-1-[amino(anilino)methylidene]-2-phenylguanidine Chemical compound C=1C=CC=CC=1N=C(N)\N=C(/N)NC1=CC=CC=C1 NTTLKRPWPKPUAI-UHFFFAOYSA-N 0.000 description 1
- BCPFWSWROVXGQA-UHFFFAOYSA-N 2-(2,4,4-trimethylpentan-2-yl)guanidine Chemical compound CC(C)(C)CC(C)(C)N=C(N)N BCPFWSWROVXGQA-UHFFFAOYSA-N 0.000 description 1
- 125000002927 2-methoxybenzyl group Chemical group [H]C1=C([H])C([H])=C(C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 description 1
- MSHFRERJPWKJFX-UHFFFAOYSA-N 4-Methoxybenzyl alcohol Chemical compound COC1=CC=C(CO)C=C1 MSHFRERJPWKJFX-UHFFFAOYSA-N 0.000 description 1
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 229940123208 Biguanide Drugs 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- BEOKBUHJDGJDKO-UHFFFAOYSA-N [Cl].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 Chemical compound [Cl].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 BEOKBUHJDGJDKO-UHFFFAOYSA-N 0.000 description 1
- 150000001409 amidines Chemical class 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000078 anti-malarial effect Effects 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 150000004283 biguanides Chemical class 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- AVPVRXORILGHNM-UHFFFAOYSA-N chlorobenzene;methanol Chemical class OC.ClC1=CC=CC=C1 AVPVRXORILGHNM-UHFFFAOYSA-N 0.000 description 1
- QGBSISYHAICWAH-UHFFFAOYSA-N dicyandiamide Chemical class NC(N)=NC#N QGBSISYHAICWAH-UHFFFAOYSA-N 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical group 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- XJUJXVATKIRSAM-UHFFFAOYSA-N fluoro(phenyl)methanol Chemical compound OC(F)C1=CC=CC=C1 XJUJXVATKIRSAM-UHFFFAOYSA-N 0.000 description 1
- 229950000289 guanoctine Drugs 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 description 1
- 229950002366 nafoxidine Drugs 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 150000003304 ruthenium compounds Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 238000009333 weeding Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/26—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hetero atoms directly attached to ring carbon atoms
- C07D251/40—Nitrogen atoms
- C07D251/48—Two nitrogen atoms
-
- 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
- C07D405/02—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 two hetero rings
- C07D405/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The present invention provides the preparation method of the s-triazine compound shown in a kind of formula (III), the preparation method is：Biguanide hydrochloride, metal Ru catalyst, alkaline matter shown in alcohol compound shown in formula (I) and formula (II) is added in solvent, 10~18h is stirred to react at 80~130 DEG C, reaction solution is post-treated afterwards obtains the s-triazine compound shown in formula (III)；Preparation method reaction condition of the present invention is mild, and raw material is easy to get, easy to operate, at low cost, there is extensive prospects for commercial application；
Description
(1) technical field
The present invention relates to a kind of preparation methods of s-triazine compound.
(2) background technology
Compound in triazine class has the multiple biological activities such as anticancer, antibacterial, antimalarial, weeding, is widely used in medicine, agriculture
The fields such as medicine.Wherein, s-triazine compound is more typical a kind of compound in triazine class, and the preparation of such compound is mainly
Pass through cyanoguanidines and nitrile compounds reaction, biguanides and ester type compound reaction, amide and dimethyl-acetal and amidine or guanidine
Reaction etc., but these synthetic methods have certain limitation.Therefore, the preparation method of s-triazine compound is studied with important
Theory significance and actual application value.
(3) content of the invention
The object of the present invention is to provide a kind of preparation methods of s-triazine compound.
The present invention adopts the following technical scheme that：
A kind of preparation method of s-triazine compound shown in formula (III), the preparation method are：
By biguanide hydrochloride, metal Ru catalyst, the alkaline matter shown in the alcohol compound shown in formula (I) and formula (II)
Add in solvent in, 10~18h is stirred to react at 80~130 DEG C, afterwards reaction solution it is post-treated obtain it is equal shown in formula (III)
Compound in triazine class；
Wherein,
R1, R2Each stand alone as hydrogen, C1~C10 alkyl or C6~C10 aryl or R1, R2N combinations between the two
Form C4~C8 heterocycles containing N or containing N, O；It is preferred that R1, R2Each stand alone as hydrogen, methyl or phenyl or R1, R2With the two it
Between N combine to form nafoxidine ring, piperidine ring or morpholine ring；
R3For hydrogen or C6~C10 aryl；It is preferred that R3For hydrogen or phenyl；
R4For C4~C8 heteroaryls containing O or S, C6~C10 aryl or the C6~C10 being substituted by one or more substituents
Aryl, the substituent group be selected from C1~C10 alkyl, C1~C10 alkoxy or halogens, the preferably described substituent group for methyl,
Methoxyl group, fluorine, chlorine or bromine；It is preferred that R4For furyl, thienyl, phenyl, p-methylphenyl, p-methoxyphenyl, O-methoxy
Phenyl, 3,4- Dimethoxyphenyls, 2,3- Dimethoxyphenyls, 2,4 dichloro benzene base, rubigan, p-bromophenyl or to fluorobenzene
Base.
In preparation method of the present invention, the alcohol compound shown in the formula (I) and the Guanoctine shown in formula (II)
The ratio between hydrochlorate, metal Ru catalyst, amount of substance of alkaline matter are 1：0.5~1.5：0.01~0.04：1.0~3.0.
The solvent is ethers, aromatic hydrocarbons, sulfoxide type or amides, is preferably tetrahydrofuran, Isosorbide-5-Nitrae-dioxane, first
Benzene, DMF or DMSO, further preferably Isosorbide-5-Nitrae-dioxane.Recommend alcohols of the volumetric usage of the solvent shown in formula (I)
The quality of compound is calculated as 10~50mL/g.
The metal Ru catalyst is divalent ruthenium or trivalent ruthenium compound, is preferably ten dicarbapentaborane rutheniums, triphenylphosphine chlorine
Change ruthenium, two (triphenylphosphine) cyclopentadiene ruthenic chlorides, ruthenium trichloride or 1,5- cyclo-octadiene ruthenous chlorides；Further preferably ten
Dicarbapentaborane ruthenium or 1,5- cyclo-octadiene ruthenous chlorides.
The alkaline matter be organic base or inorganic base, be preferably potassium tert-butoxide, sodium methoxide or cesium carbonate, further it is excellent
Elect potassium tert-butoxide as.
Following method can be used in the post processing：After reaction, the water (volumetric usage of usual water is added in reaction solution
It is 1.0~3.0 times of reaction solution volume), it is then extracted with ethyl acetate, collected organic layer is dried with anhydrous sodium sulfate, mistake
Filter concentrates filtrate, and gained concentrate carries out column chromatography for separation, with dichloromethane：Methanol volume ratio is 50：1 mixed liquor is to wash
De- agent, collects the eluent containing target compound, removes drying after solvent under reduced pressure, obtains target compound shown in formula (III).
The advantageous effect of preparation method of the present invention is that the technological reaction mild condition, raw material is easy to get, easy to operate, into
This is low, there is extensive prospects for commercial application.
(4) specific embodiment
Below by specific embodiment, the present invention is further illustrated, but protection scope of the present invention is not limited in
This.Embodiment 1：The preparation of compound (III-1)
In reaction vessel, addition Metformin (0.1653g, 0.9954mmol), benzylalcohol (0.1082g,
1.0002mmol), 1,5- cyclo-octadiene ruthenous chloride (0.0056g, 0.02mmol), potassium tert-butoxide (0.2250g,
2.0052mmol), Isosorbide-5-Nitrae-dioxane (4mL), be stirred to react in 100 DEG C of oil baths 15 it is small when；After reaction, water is added
(10mL) is extracted with ethyl acetate (10mL × 3), merges organic layer, is dried with anhydrous sodium sulfate, filters, and concentrates filtrate, gained
Concentrate carries out column chromatography for separation, and eluant, eluent is dichloromethane：Methanol=50：1(V：V), R is collectedfThe elution of value 0.3~0.35
Liquid (TLC is monitored, the same eluant, eluent of solvent), vacuum distillation are dried to obtain target compound (III-1) 0.1592g, yield is
74%.
1H NMR(500MHz,CDCl3):δ8.38–8.37(m,2H),7.52–7.47(m,1H),7.47–7.43(m,2H),
5.37(s,2H),3.31(s,3H),3.17(s,3H).
Embodiment 2：
1,5- cyclo-octadiene ruthenous chlorides are changed to ten dicarbapentaborane rutheniums (0.0128g, 0.02mmol), other operations are the same as implementation
Example 1 finally obtains target compound (III-1) 0.1586g, yield 74%.
Embodiment 3：
1,5- cyclo-octadiene ruthenous chlorides are changed to triphenylphosphine ruthenic chloride (0.0182g, 0.02mmol), other operations are same
Embodiment 1 finally obtains target compound (III-1) 0.1180g, yield 55%.
Embodiment 4：
By 1,5- cyclo-octadiene ruthenous chlorides be changed to two (triphenylphosphine) cyclopentadiene ruthenic chlorides (0.0152g,
0.02mmol), other operations finally obtain target compound (III-1) 0.1050g, yield 49% with embodiment 1.
Embodiment 5：
1,5- cyclo-octadiene ruthenous chlorides are changed to a water ruthenium trichloride (0.0044g, 0.02mmol), other operations are the same as real
Example 1 is applied, finally obtains target compound (III-1) 0.1342g, yield 62%.
Embodiment 6：
Solvent Isosorbide-5-Nitrae-dioxane is changed to DMSO (4mL), other operations finally obtain target compound with embodiment 1
(III-1) 0.0530g, yield 25%.
Embodiment 7：
Solvent Isosorbide-5-Nitrae-dioxane is changed to tetrahydrofuran (4mL), other operations finally obtain targeted with embodiment 1
Close object (III-1) 0.1020g, yield 47%.
Embodiment 8：
Solvent Isosorbide-5-Nitrae-dioxane is changed to DMF (4mL), other operations finally obtain target compound with embodiment 1
(III-1) 0.0114g, yield 5%.
Embodiment 9：
Solvent Isosorbide-5-Nitrae-dioxane is changed to toluene (4mL), other operations finally obtain target compound with embodiment 1
(III-1) 0.0650g, yield 30%.
Embodiment 10：
Potassium tert-butoxide is changed to cesium carbonate (0.3250g, 2.0mmol), other operations finally obtain target with embodiment 1
Compound (III-1) 0.0129g, yield 6%.
Embodiment 11：
Potassium tert-butoxide is changed to sodium methoxide (0.0549g, 2.0mmol), other operations finally obtain target with embodiment 1
Compound (III-1) 0.0151g, yield 7%.
Embodiment 12：
Reaction temperature is changed to 80 DEG C, other operations finally obtain target compound (III-1) with embodiment 1
0.1334g, yield 62%.
Embodiment 13：
Reaction temperature is changed to 130 DEG C, other operations finally obtain target compound (III-1) with embodiment 1
0.1238g, yield 58%.
Embodiment 14：
The amount of 1,5- cyclo-octadiene ruthenous chlorides is changed to 0.0115g, 0.04mmol, other operations are with embodiment 1, finally
Obtain target compound (III-1) 0.1327g, yield 60%.
Embodiment 15：
The amount of 1,5- cyclo-octadiene ruthenous chlorides is changed to 0.0027g, 0.01mmol, other operations are with embodiment 1, finally
Obtain target compound (III-1) 0.1260g, yield 58%.
Embodiment 16：
The amount of potassium tert-butoxide is changed to 0.3369g, 3.0mmol, other operations finally obtain target chemical combination with embodiment 1
Object (III-1) 0.1045g, yield 49%.
Embodiment 17：
The amount of potassium tert-butoxide is changed to 0.1136g, 1.0mmol, other operations finally obtain target chemical combination with embodiment 1
Object (III-1) 0.0203g, yield 9%.
Embodiment 18：
To be changed in reaction time 18 it is small when, other operation with embodiment 1, finally obtain target compound (III-1)
0.1208g, yield 56%.
Embodiment 19：
To be changed in reaction time 10 it is small when, other operation with embodiment 1, finally obtain target compound (III-1)
0.1012g, yield 47%.
Embodiment 20：
The amount of Metformin is changed to 0.2478g, 1.5mmol, other operations finally obtain mesh with embodiment 1
Mark compound (III-1) 0.0460g, yield 21%.
Embodiment 21：
The amount of benzylalcohol is changed to 0.1622g, 1.5mmol, other operations finally obtain target compound with embodiment 1
(III-1) 0.1284g, yield 60%.
Embodiment 22：The preparation of compound (III-2)
Operation simply changes benzylalcohol into P-methoxybenzyl alcohol (0.1516g, 1.0973mmol), mesh is made with embodiment 1
Mark compound (III-2) 0.1909g, yield 71%.
1H NMR(500MHz,CDCl3):δ 8.35 (d, J=8.8Hz, 2H), 6.96 (d, J=8.8Hz, 2H), 5.18 (s,
2H),3.87(s,3H),3.29(s,3H)3.17(s,3H).
Embodiment 23：The preparation of compound (III-3)
Operation simply changes benzylalcohol into 4- chlorobenzene methanols (0.1436g, 1.0072mmol), targeted is made with embodiment 1
Close object (III-3) 0.1555g, yield 62%.
1H NMR(500MHz,CDCl3):δ 8.32 (d, J=8.6Hz, 2H), 7.42 (d, J=8.6Hz, 2H), 5.12 (s,
2H),3.30(s,3H),3.17(s,3H).
Embodiment 24：The preparation of compound (III-4)
Operation simply changes benzylalcohol into 3,4- 3,5-dimethoxybenzoic alcohols (0.1676g, 0.9965mmol), makes with embodiment 1
Obtain target compound (III-4) 0.2274g, yield 83%.
1H NMR(500MHz,CDCl3):δ 8.03 (dd, J=8.5Hz, 1.9Hz, 1H), 7.96 (d, J=1.9Hz, 1H),
6.92 (d, J=8.5Hz, 1H), 5.23 (s, 2H), 3.98 (s, 3H), 3.94 (s, 3H), 3.29 (s, 3H), 3.16 (s, 3H)
Embodiment 25：The preparation of compound (III-5)
Operation simply changes benzylalcohol into 4- methylbenzyl alcohols (0.1244g, 1.002mmol), target is made with embodiment 1
Compound (III-5) 0.1474g, yield 65%.
1H NMR(500MHz,CDCl3):δ 8.27 (d, J=8.2Hz, 2H), 7.25 (d, J=8.2Hz, 2H), 5.13 (s,
2H),3.30(s,3H),3.17(s,3H),2.42(s,3H).
Embodiment 26：The preparation of compound (III-6)
Operation simply changes benzylalcohol into 2,3- 3,5-dimethoxybenzoic alcohols (0.1668g, 0.9917mmol), makes with embodiment 1
Obtain target compound (III-6) 0.2004g, yield 73%.
1H NMR(500MHz,CDCl3):δ 7.25 (dd, J=7.8,1.5Hz, 1H), 7.11 (t, J=8.0Hz, 1H),
6.99 (dd, J=8.2,1.5Hz, 1H), 3.22 (s, 3H), 3.16 (s, 3H)
Embodiment 27：The preparation of compound (III-7)
Operation simply changes benzylalcohol into 2- thenyl alcohols (0.1365g, 1.1965mmol), targeted is made with embodiment 1
Close object (III-7) 0.1386g, yield 62%.
1H NMR(500MHz,CDCl3):δ 7.98 (dd, J=3.7,1.2Hz, 1H), 7.46 (dd, J=5.0,1.2Hz,
1H), 7.12 (dd, J=5.0,3.7Hz, 1H), 5.20 (s, 2H), 3.26 (s, 3H), 3.15 (s, 3H)
Embodiment 28：The preparation of compound (III-8)
Operation simply changes benzylalcohol into 2- furancarbinols (0.1257g, 1.2816mmol), targeted is made with embodiment 1
Close object (III-8) 0.1317g, yield 64%.
1H NMR(500MHz,CDCl3) δ 7.57 (dd, J=1.6,0.8Hz, 1H), 7.28 (dd, J=3.4,0.8Hz,
1H), 6.51 (dd, J=3.4,1.6Hz, 1H), 5.68 (s, 2H), 3.23 (s, 3H), 3.12 (s, 3H)
Embodiment 29：The preparation of compound (III-9)
Operation simply changes benzylalcohol into 2- methoxy benzyl alcohols (0.1379g, 0.9981mmol), mesh is made with embodiment 1
Mark compound (III-9) 0.1675g, yield 68%.
1H NMR(500MHz,CDCl3):δ 7.67 (dd, J=7.5,1.8Hz, 1H), δ 7.38 (ddd, J=8.3,7.5,
1.8Hz, 1H), 7.02 (td, J=7.5,1Hz, 1H), 6.99 (d, J=8.3Hz, 1H), 5.25 (s, 2H), 3.87 (s, 3H),
3.22(s,3H),3.15(s,3H).
Embodiment 30：The preparation of compound (III-10)
Operation simply changes benzylalcohol into 2,4-DCBA (0.1776g, 1.0033mmol), mesh is made with embodiment 1
Mark compound (III-10) 0.0819g, yield 29%.
1H NMR(500MHz,CDCl3):δ 7.69 (d, J=8.3Hz, 1H), 7.48 (d, J=2.0Hz, 1H), 7.31 (dd,
J=8.3,2.0Hz, 1H), 5.28 (s, 2H), 3.23 (s, 3H), 3.16 (s, 3H)
Embodiment 31：The preparation of compound (III-11)
Operation with embodiment 1, simply by Metformin change into abitilguanide hydrochloride (0.2071g,
0.9973mmol), target compound (III-11) 0.1690g, yield 66% is made.
1H NMR(500MHz,CDCl3):δ 8.42-8.30 (m, 2H), 7.55-7.48 (m, 1H), 7.45 (t, J=7.4Hz,
2H),5.22(s,2H),3.93(br,4H),3.83–3.63(m,4H).
Embodiment 32：The preparation of compound (III-12)
Operation with embodiment 1, simply by Metformin change into nafoxidine biguanide hydrochloride (0.1284g,
0.6731 mmol), target compound (III-12) 0.0962g, yield 60% is made.
1H NMR(500MHz,CDCl3):δ8.45–8.30(m,2H),7.50–7.43(m,3H),5.17(s,2H),3.75
(br,2H),3.58(br,2H),2.09–1.92(m,4H).
Embodiment 33：The preparation of compound (III-13)
Operation with embodiment 1, simply by Metformin change into hexahydropyridine biguanide hydrochloride (0.1885g,
0.9164mmol), target compound (III-13) 0.1626g, yield 70% is made.
1H NMR(500MHz,CDCl3):δ8.39–8.31(m,2H),7.52–7.43(m,3H),5.21(s,2H),3.95
(br,2H),3.81(br,2H),1.75–1.57(m,6H).
Embodiment 34：The preparation of compound (III-14)
Operation with embodiment 1, simply by Metformin change into 1,5- diphenyl biguanide hydrochloride (0.2890g,
0.9974mmol), target compound (III-14) 0.2958g, yield 87% is made.
1H NMR(500MHz,CDCl3):δ 8.44 (d, J=7.3Hz, 2H), 7.68 (d, J=7.7Hz, 4H), 7.58-
7.54 (m, 1H), 7.53-7.49 (m, 2H), 7.39 (t, J=7.9Hz, 4H), 7.31 (br, 2H), 7.16-7.12 (m, 2H)
Embodiment 35：The preparation of compound (III-15)
Operation simply changes Metformin into 1,1- dimethyl -5- phenyl biguanide hydrochlorides with embodiment 1
Target compound (III-15) 0.1336g, yield 46% is made in (0.2436g, 1.0078mmol).
1H NMR(500MHz,CDCl3) δ 8.48-8.41 (m, 2H), 7.71 (dd, J=8.6,1.0Hz, 2H), 7.55-
7.48 (m, 3H), 7.39-7.35 (m, 2H), 7.20 (br, 1H), 7.08 (tt, J=7.5,1.1Hz, 1H), 3.36 (s, 3H),
3.26(s,3H).
Embodiment 36：The preparation of compound (III-16)
Operation with embodiment 1, simply by Metformin change into 1- phenyl biguanides hydrochloride (0.2138g,
1.0006mmol), target compound (III-16) 0.2116g, yield 80% is made.
1H NMR(500MHz,CDCl3):δ 8.38 (d, J=7.3Hz, 2H), 7.66 (d, J=7.9Hz, 2H), 7.54 (t, J
=7.3Hz, 1H), 7.49 (t, J=7.4Hz, 2H), 7.38 (t, J=7.9Hz, 2H), 7.25 (s, 1H), 7.12 (t, J=
7.4Hz,1H),5.36(s,2H).
Embodiment 37：The preparation of compound (III-17)
Benzylalcohol is simply changed to meta-methoxy benzylalcohol (0.1326g, 0.9598mmol), target is made by operation with embodiment 1
Compound (III-17) 0.1298g, yield 55%.
1H NMR(500MHz,CDCl3):δ 7.98 (d, J=7.9Hz, 1H), 7.94 (d, J=2.1Hz, 1H), 7.37 (t, J
=7.9Hz, 1H), 7.05 (dd, J=7.9,2.1Hz, 1H), 5.10 (s, 2H), 3.90 (s, 3H), 3.30 (s, 3H), 3.18 (s,
3H).
c(III-17)
Embodiment 38：The preparation of compound (III-18)
Benzylalcohol is simply changed to bromobenzyl alcohol (0.1974g, 1.0510mmol) with embodiment 1, target chemical combination is made by operation
Object (III-18) 0.1506g, yield 51%.
1H NMR(500MHz,CDCl3):δ8.30–8.19(m,2H),7.60–7.53(m,2H),5.21(s,2H),3.29
(s,3H),3.17(s,3H).
Embodiment 39：The preparation of compound (III-19)
Benzylalcohol is simply changed to fluoro benzyl alcohol (0.1970g, 1.5621mmol) with embodiment 1, target chemical combination is made by operation
Object (III-18) 0.1256g, yield 53%.
1H NMR(500MHz,CDCl3):δ8.54–8.27(m,2H),7.15–7.07(m,2H),5.26(s,2H),3.29
(s,3H),3.17(s,3H).
。
Claims (9)
1. the preparation method of the s-triazine compound shown in a kind of formula (III), which is characterized in that the preparation method is：
Biguanide hydrochloride, metal Ru catalyst, alkaline matter shown in alcohol compound shown in formula (I) and formula (II) is added in
In solvent, 10~18h is stirred to react at 80~130 DEG C, reaction solution is post-treated afterwards obtains the s-triazine shown in formula (III)
Class compound；
Alcohol compound shown in the formula (I) and biguanide hydrochloride, metal Ru catalyst, the alkaline matter shown in formula (II)
The ratio between amount of substance is 1：0.5~1.5：0.01~0.04：1.0~3.0；
Wherein,
R1, R2Each stand alone as hydrogen, C1~C10 alkyl or C6~C10 aryl or R1, R2N between the two, which combines to be formed, to be contained
N or C4~C8 heterocycles containing N, O；
R3For hydrogen or C6~C10 aryl；
R4For C4~C8 heteroaryls containing O or S, C6~C10 aryl or the C6~C10 aryl being substituted by one or more substituents,
The substituent group is selected from C1~C10 alkyl, C1~C10 alkoxy or halogens.
2. preparation method as described in claim 1, which is characterized in that the R1, R2Hydrogen, methyl or phenyl each are stood alone as,
Or R1, R2N between the two combines to form nafoxidine ring, piperidine ring or morpholine ring.
3. preparation method as described in claim 1, which is characterized in that the R3For hydrogen or phenyl.
4. preparation method as described in claim 1, which is characterized in that the R4For furyl, thienyl, phenyl, to methyl
Phenyl, p-methoxyphenyl, o-methoxyphenyl, 3,4- Dimethoxyphenyls, 2,3- Dimethoxyphenyls, 2,4 dichloro benzene
Base, rubigan, p-bromophenyl or p-fluorophenyl.
5. preparation method as described in claim 1, which is characterized in that the solvent for tetrahydrofuran, Isosorbide-5-Nitrae-dioxane,
Toluene, DMF or DMSO.
6. preparation method as described in claim 1, which is characterized in that alcohol of the volumetric usage of the solvent shown in formula (I)
The quality of class compound is calculated as 10~50mL/g.
7. preparation method as described in claim 1, which is characterized in that the metal Ru catalyst is ten dicarbapentaborane rutheniums, three
Phenylphosphine ruthenic chloride, two (triphenylphosphine) cyclopentadiene ruthenic chlorides, ruthenium trichloride or 1,5- cyclo-octadiene ruthenous chlorides.
8. preparation method as described in claim 1, which is characterized in that the alkaline matter for potassium tert-butoxide, sodium methoxide or
Cesium carbonate.
9. preparation method as described in claim 1, which is characterized in that the post processing is with the following method：Reaction terminates
Afterwards, water is added in reaction solution, is then extracted with ethyl acetate, collected organic layer is dried with anhydrous sodium sulfate, filtering, concentration filter
Liquid, gained concentrate carries out column chromatography for separation, with dichloromethane：Methanol volume ratio is 50：1 mixed liquor is eluant, eluent, is collected
Eluent containing target compound removes drying after solvent under reduced pressure, obtains target compound shown in formula (III).
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| CN108395434A (en) * | 2018-05-02 | 2018-08-14 | 浙江工业大学 | A kind of preparation method of dihydro [1,3,5] triazine and benzimidazoles compound |
| CN108840829A (en) * | 2018-05-02 | 2018-11-20 | 浙江工业大学 | A kind of preparation method of 4- aryl -1,3,5- triazine -2- ketone compounds |
| CN108546252A (en) * | 2018-05-02 | 2018-09-18 | 浙江工业大学 | Triazinone compounds and its preparation method and application |
| CN109053612A (en) * | 2018-06-29 | 2018-12-21 | 浙江工业大学 | A kind of phenethyl replaces 1,3,5- compound in triazine class and its preparation method and application |
| CN108752284A (en) * | 2018-06-29 | 2018-11-06 | 浙江工业大学 | Two amido-s- compound in triazine class of one kind and its preparation method and application |
| CN108864059A (en) * | 2018-06-29 | 2018-11-23 | 浙江工业大学 | A kind of s- pyrrolotriazine derivatives and its preparation method and application |
| CN112250639B (en) * | 2020-11-19 | 2022-05-24 | 浙江工业大学 | Heterocyclic substituted arylamine compound and preparation method and application thereof |
| CN113149917B (en) * | 2021-04-30 | 2023-01-10 | 浙江工业大学 | Preparation method of triazine compound |
| CN113461660B (en) * | 2021-06-11 | 2022-08-02 | 浙江大学 | 2,4, 6-trisubstituted-1, 3, 5-s-triazine compound, preparation and application thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1281450A (en) * | 1997-10-07 | 2001-01-24 | 拜尔公司 | Substituted 2,4-diamino-1,3,5-triazine and their use as herbicides |
| CN101602757A (en) * | 2009-07-14 | 2009-12-16 | 丹东恒悦新材料有限公司 | 4-substituent-2-amido pyrimidine compound and preparation method thereof |
| CN102036970A (en) * | 2008-05-23 | 2011-04-27 | 博希尔公司 | Process for the synthesis of 3,6-dihydro-1,3,5-triazine derivatives |
| CN104114543A (en) * | 2012-01-06 | 2014-10-22 | 安吉奥斯医药品有限公司 | Therapeutically active compounds and their methods of use |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1316490B1 (en) * | 2001-11-23 | 2006-03-15 | Conception et Développement Michelin S.A. | Electric steering for vehicles |
| DE102007054416A1 (en) * | 2007-11-13 | 2009-05-14 | Studiengesellschaft Kohle Mbh | Process for the preparation of 3,6-dihydro-1,3,5-triazine derivatives for the treatment of diseases associated with insulin resistance syndrome |
| JP2010072340A (en) * | 2008-09-18 | 2010-04-02 | Fujifilm Corp | Photosensitive composition, photosensitive film, photosensitive laminate, permanent pattern forming method, and printed circuit board |
-
2016
- 2016-03-25 CN CN201610177528.5A patent/CN105753801B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1281450A (en) * | 1997-10-07 | 2001-01-24 | 拜尔公司 | Substituted 2,4-diamino-1,3,5-triazine and their use as herbicides |
| CN102036970A (en) * | 2008-05-23 | 2011-04-27 | 博希尔公司 | Process for the synthesis of 3,6-dihydro-1,3,5-triazine derivatives |
| CN101602757A (en) * | 2009-07-14 | 2009-12-16 | 丹东恒悦新材料有限公司 | 4-substituent-2-amido pyrimidine compound and preparation method thereof |
| CN104114543A (en) * | 2012-01-06 | 2014-10-22 | 安吉奥斯医药品有限公司 | Therapeutically active compounds and their methods of use |
Non-Patent Citations (9)
| Title |
|---|
| 2-氨基-4-二甲氨基-6-取代-1,3,5-三嗪化合物的合成;刘畅;《广东药学院学报》;20050430;第21卷(第2期);第115-116页图1、表1以及实验部分1.4 * |
| Dehydrogenation as a Substrate-Activating Strategy in Homogeneous Transition-Metal Catalysis;Graham E. Dobereiner,等;《Chemical Reviews》;20091125;第110卷(第2期);第681-703页尤其是第685页方案8、第686页表1和第687页方案13 * |
| High yielding microwave-assisted synthesis of 2-(arylmethyl)amino-4-arylamino-6-alkyl-1,3,5-triazines;Huixiong Chen,等;《Tetrahedron Letters》;20100414;第51卷(第24期);第3174-3176页 * |
| Novel Inhibitors of Erm Methyltransferases from NMR and Parallel Synthesis;Philip J. Hajduk,等;《Journal of Medicinal Chemistry》;19990904;第42卷(第19期);第3852-3859页 * |
| Optimised synthesis of diamino-triazinylmethyl benzoates as inhibitors of Rad6B ubiquitin conjugating enzyme;Hend Kothayer,等;《Tetrahedron Letters》;20141029;第55卷(第51期);第7015-7018页 * |
| Ruthenium-Catalyzed Amination of Secondary Alcohols Using Borrowing Hydrogen Methodology;Kostiantyn O. Marichev,等;《ACS Catalysis》;20160223;第6卷(第期);第2205-2210页 * |
| Ruthenium-Catalyzed N‑Alkylation of Amines with Alcohols under Mild Conditions Using the Borrowing Hydrogen Methodology;Arrey B. Enyong,等;《The Journal of Organic Chemistry》;20140709;第79卷(第16期);第7553-7563页 * |
| THE RUTHENIUM CATALYZED N-ALKYLATION AND N-HETEROCYCLIZATION OF ANILINE USING ALCOHOLS AND ALDEHYDES;Yoshihisa Watanabe,等;《Tetrahedron Letters》;19811231;第22卷(第28期);第2667-2670页 * |
| 三嗪类衍生物的研究;刘畅,等;《沈阳药科大学学报》;20040731;第21卷(第4期);第264-265页图1，实验部分1.3以及表1 * |
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Effective date of registration: 20240324 Address after: 314000 building 3, Jiake Life Science Park, 3556 linggongtang Road, Daqiao Town, Nanhu District, Jiaxing City, Zhejiang Province Patentee after: Zhejiang Arthur Pharmaceutical Co.,Ltd. Country or region after: China Address before: 310014 science and technology office, Zhejiang University of Technology, No. 18 Chao Wang Road, Xiacheng District, Hangzhou, Zhejiang Patentee before: JIANG University OF TECHNOLOGY Country or region before: China |
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