CN107880039B - A kind of preparation method of pyrido [1,2-a] [1,3,5]-triazine -4- ketone compound - Google Patents
A kind of preparation method of pyrido [1,2-a] [1,3,5]-triazine -4- ketone compound Download PDFInfo
- Publication number
- CN107880039B CN107880039B CN201711063609.3A CN201711063609A CN107880039B CN 107880039 B CN107880039 B CN 107880039B CN 201711063609 A CN201711063609 A CN 201711063609A CN 107880039 B CN107880039 B CN 107880039B
- Authority
- CN
- China
- Prior art keywords
- triazine
- pyrido
- ketone compound
- preparation
- pyridine
- 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.)
- Active
Links
- NNVJXTBUNOYPEE-UHFFFAOYSA-N 4h-pyrido[1,2-a][1,3,5]triazine Chemical compound C1=CC=CN2CN=CN=C21 NNVJXTBUNOYPEE-UHFFFAOYSA-N 0.000 title claims abstract description 24
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 36
- 238000006243 chemical reaction Methods 0.000 claims abstract description 19
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims abstract description 18
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims abstract description 18
- 150000002460 imidazoles Chemical class 0.000 claims abstract description 16
- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 claims abstract description 11
- 235000019394 potassium persulphate Nutrition 0.000 claims abstract description 11
- 239000003960 organic solvent Substances 0.000 claims abstract description 10
- 239000012286 potassium permanganate Substances 0.000 claims abstract description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- 239000000460 chlorine Substances 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- CFXQEHVMCRXUSD-UHFFFAOYSA-N 1,2,3-Trichloropropane Chemical group ClCC(Cl)CCl CFXQEHVMCRXUSD-UHFFFAOYSA-N 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- -1 Ketone compound Chemical class 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 238000000034 method Methods 0.000 abstract description 11
- JIHQDMXYYFUGFV-UHFFFAOYSA-N 1,3,5-triazine Chemical compound C1=NC=NC=N1 JIHQDMXYYFUGFV-UHFFFAOYSA-N 0.000 abstract description 7
- 239000002994 raw material Substances 0.000 abstract description 7
- 238000012805 post-processing Methods 0.000 abstract description 3
- 238000006467 substitution reaction Methods 0.000 abstract description 3
- 239000003054 catalyst Substances 0.000 abstract description 2
- 229910001385 heavy metal Inorganic materials 0.000 abstract description 2
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 125000003118 aryl group Chemical group 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000007800 oxidant agent Substances 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- JMANVNJQNLATNU-UHFFFAOYSA-N oxalonitrile Chemical compound N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical class ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 206010014950 Eosinophilia Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- XLJMAIOERFSOGZ-UHFFFAOYSA-M cyanate Chemical compound [O-]C#N XLJMAIOERFSOGZ-UHFFFAOYSA-M 0.000 description 1
- MCWXGJITAZMZEV-UHFFFAOYSA-N dimethoate Chemical compound CNC(=O)CSP(=S)(OC)OC MCWXGJITAZMZEV-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 238000006452 multicomponent reaction Methods 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 1
- 229910052939 potassium sulfate Inorganic materials 0.000 description 1
- 235000011151 potassium sulphates Nutrition 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000003215 serotonin 5-HT2 receptor antagonist Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000005979 thermal decomposition reaction Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The invention discloses a kind of pyridos [1,2-a] [1,3,5]-triazine -4- ketone compound preparation method, include the following steps: potassium peroxydisulfate, potassium permanganate, imidazoles [1,2- α] pyridine and sodium azide be added in organic solvent, be heated to 120~140 DEG C and reacted, after fully reacting, post-processing obtains the pyrido [1,2-a] [1,3,5]-triazine -4- ketone compound.The preparation method step is simple, raw material is conveniently easy to get, and reaction under the conditions of anhydrous and oxygen-free without carrying out, in addition without using heavy metal as catalyst, it can also be by designing the pyrido [1,2-a] [1,3 for synthesizing different the position of substitution diversifications and replacing, 5]-triazine -4- ketone compound, convenient for having widened the practicability of the method while operation.
Description
Technical field
The invention belongs to organic synthesis field more particularly to a kind of pyrido [1,2-a] [1,3,5]-triazine -4- assimilations
Close the preparation method of object.
Background technique
[1,3,5]-triazine -4- ketone compound is widely used in organic synthesis as a kind of important nitrogenous condensed hetero ring, raw
Object and drug molecule field (J.Med.Chem.1998,41,2985-2993), many important molecular skeletons and synthesis precursor
All contain the structural unit of [1,3,5]-triazine -4- ketone.Such as artificial carbon's deoxynucleoside precursor, Asia can be effectively converted into
Phosphamide reagent is used for DNA molecular synthesizer；In addition, [1,3,5]-triazine -4- ketone derivatives containing pyrazole ring can be used as
CRHR-1/5-HT2Antagonist；It is also used as the inhibitor etc. of eosinophilia:
Nowadays it is prepared in document report there are mainly three types of pyrido [1,2-a] [1,3,5]-triazine -4- ketone methods: one
Kind is by N- fluorinated pyridine salt, and (A.S.Kiselyov, L. Strekowski, Tetrahedron is made in cyanate and nitrile
Letters 1994,35,207-210.).Second is by 2-aminopyridine and trimethyl silicane based isocyanate or carbethoxyl group
Isothiocyanates mercury salt catalysis under synthesis (H. Oda, T.Hanami, T.Iwashita, M.Kojima, M.Itoh,
Y.Hayashizaki,Tetrahedron 2007,63,11021-11029；M.Kopp,J.-C.Lancelot,S.Dagdag,
H.Miel,S.Rault, J.Heterocyclic Chem.2002,39,1061-1064.).The third is by 2-aminopyridine
Reacted with nitrogen-benzyloxycarbonyl group -2,2,2- trifluoromethanesulfonyl imide acetyl group chlorine be made (N.V.Mel ' nichenko, V.N. Tkachuk,
E.B.Rusanov,V.A.Sukach,V.I.Boiko,M.V.Vovk,Russian Journal of Organic
Chemistry,2013,49,119-122).Pyrrole is synthesized by the methods of multi-component reaction and condensation reaction there is also some
Pyridine simultaneously [1,2-a] [1,3,5]-triazine -4- ketone compound.
But most of method described above has some limitations, for example substrate need to be functionalized in advance, be needed more
Synthesis step is walked, regioselectivity is poor, and reaction yield is low, and substrate popularity is narrow etc..Based on this, we have developed a kind of with convenient
Imidazoles [1, the 2- α] pyridine and sodium azide being easy to get are starting material, what what potassium peroxydisulfate and potassium permanganate promoted be simple and efficient
The synthetic method of polysubstituted pyridine simultaneously [1,2-a] [1,3,5]-triazine -4- ketone.
Summary of the invention
The present invention provides a kind of pyrido [1,2-a] [1,3,5]-triazine -4- ketone compound preparation method, the preparations
Method is easy to operate, and raw material is conveniently easy to get, and is not necessarily to anhydrous and oxygen-free condition, while avoiding making for toxic heavy metal catalyst
With convenient for operation and application；This method can also easily be extended to gram-grade, and providing for industrial large-scale production and application can
Energy.
A kind of preparation method of pyrido [1,2-a] [1,3,5]-triazine -4- ketone compound, includes the following steps: mistake
Potassium sulfate, potassium permanganate, imidazoles [1,2- α] pyridine and sodium azide are added in organic solvent, are heated to 120~140 DEG C
It is reacted, after fully reacting, post-processing obtains pyrido [1,2-a] [1,3, the 5]-triazine -4- ketone compound；
Shown in the structure such as formula (II) of described imidazoles [1,2- α] pyridine:
Shown in pyrido [1,2-a] [1,3,5]-triazine -4- ketone compound structure such as formula (I):
In formula (I)~(II), R1Selected from H, substitution or unsubstituted C1~C4Alkyl, aryl, trifluoromethyl or halogen
One or more of；
R2To replace or unsubstituted aryl, the substituent group on the aryl are selected from trifluoromethyl, cyano ,-COOMe, C1
~C4Alkyl or halogen；
The molar ratio of the potassium peroxydisulfate and potassium permanganate is 3:0.2~1.0；
R1, R2The position of substitution of upper aryl can be ortho position, contraposition or meta position.
Reaction equation is as follows:
Imidazoles [1,2- α] 3- Azide processes of pyridine that oxidation promotes may be experienced in reaction, which may also
For free radical process；Aryl azide is released nitrogen by thermal decomposition, forms nitrene；The azacyclo- of intramolecular cyclization generation high rigidity
Propylene；Then similar azepine Baeyer-Wei Leige oxidation process occurs under the facilitation of potassium peroxydisulfate and obtains final pyridine
And [1,2-a] [1,3,5]-triazine -4- ketone compound.
In the present invention, available last handling process includes: filtering, and silica gel mixed sample is finally obtained by column chromatographic purifying
Corresponding pyrido [1,2-a] [1,3,5]-triazine -4- ketone compound, uses column chromatographic purifying for technology hand commonly used in the art
Section.
Preferably, R1For selected from H, methyl, halogen, one or more of trifluoromethyl or phenyl, at this point, institute
Imidazoles [1, the 2- α] pyridine stated is easy to be made, and the yield reacted is higher.
Preferably, R2To replace or unsubstituted phenyl, the substituent group on the phenyl are selected from trifluoromethyl, cyanogen
Base ,-COOMe, methyl or chlorine, at this point, described imidazoles [1, the 2- α] pyridine is easy to get, and the yield reacted is higher.
The sodium azide it is cheap, be widely applied in industry, relative to described to imidazoles [1,2- α]
The dosage of pyridine is excessive, preferably, with molar amount, imidazoles [1,2- α] pyridine: sodium azide: potassium peroxydisulfate: permanganic acid
Potassium=1:1~3:2~4:0.2~1；As a further preference, with molar amount, imidazoles [1,2- α] pyridine: sodium azide:
Potassium peroxydisulfate: potassium permanganate=1:2:3:0.5.
Preferably, the time of the reaction is 8~16 hours, reaction time too long increase reaction cost, on the contrary then
It is difficult to ensure the complete of reaction.
In the present invention, the organic solvent that raw material sufficiently dissolves can be made reaction, but reaction efficiency difference is larger,
Preferably containing the non-protonic solvent of chlorine, non-protonic solvent containing chlorine can effectively promote the progress of reaction；Preferably, institute
The organic solvent stated is 1,2,3- trichloropropane or 1,2- dichloroethanes；As a further preference, the organic solvent
It is 1,2,3- trichloropropanes, at this point, various raw materials can be with higher conversion at product.
The dosage of the organic solvent can preferably dissolve raw material, and imidazoles [1,2- α] pyridine of 1mmol makes
The amount of organic solvent is about 5~6mL.
Preferably, the oxidant is potassium peroxydisulfate and potassium permanganate, both oxidant prices are relatively cheap, and
And reaction efficiency is higher when being combined using two kinds of oxidants.
As a further preference, the pyrido [1,2-a] [1,3,5]-triazine -4- ketone compound is formula (I-
1) one of compound shown in-formula (I-5):
If formula (I-1)-(I-5) compound represented three is known compound, two are noval chemical compound.
In above-mentioned preparation method, the sodium azide and potassium peroxydisulfate and potassium permanganate generally use commercial product,
It can readily obtain from the market, the imidazoles [1,2- α] pyridine can be by corresponding 2-aminopyridine and 2- bromo fragrance
Ethyl ketone is simple and efficient to be prepared.
Compared with the existing technology, the beneficial effects of the present invention are embodied in: the preparation methods to be not necessarily to anhydrous and oxygen-free condition, is easy to
Operation, post-processing are easy；Reaction raw materials are conveniently easy to get, and reaction substrate designability is strong, and substrate functional group good compatibility can basis
Actual needs design synthesizes different substituted pyrido [1,2-a] [1,3,5]-triazine -4- ketone compounds, practicability compared with
By force.
Specific embodiment
The present invention will be further described combined with specific embodiments below.
Potassium peroxydisulfate, potassium permanganate, imidazoles [1,2- α] is added in the Schlenk pipe of 35ml according to the raw material proportioning of table 1
Pyridine (II) and organic solvent 2ml, are mixed evenly, according to table 2 reaction condition after the reaction was completed, filtering, silica gel mixed sample,
Corresponding pyrido [1,2-a] [1,3,5]-triazine -4- ketone compound (I) is obtained by column chromatographic purifying, reaction process is as follows
Shown in formula:
Table 1
Table 2
In Tables 1 and 2, T is reaction temperature, and t is reaction time, CF3For trifluoromethyl, CN is cyano, and Ph is phenyl.
The structure confirmation data of compound is prepared in Examples 1 to 5:
Be prepared by embodiment 1 pyrido [1,2-a] [1,3,5]-triazine -4- ketone compound (I-1, No. CAS:
2097149-27-2) nuclear magnetic resonance (1H NMR and13C NMR) detection data are as follows:
1H NMR(CDCl3, 400MHz) δ (ppm) 9.19 (d, 1H, J=1.6Hz), 8.55 (m, 2H), 8.03 (dd, 1H,
J1=9.2Hz, J2=2.0Hz), 7.57 (m, 2H), 7.49 (t, 2H, J=7.2 Hz)13C NMR(CDCl3,100MHz)δ
(ppm)169.7,154.2,150.2,144.7,135.4, 133.0,130.1,129.6,128.5,126.4,112.3.HRMS
(ES+-TOF)calcd for C13H9BrN3O+(M+H+):301.9924,found:301.9933.
Be prepared by embodiment 2 pyrido [1,2-a] [1,3,5]-triazine -4- ketone compound (I-2, No. CAS: new
Compound) nuclear magnetic resonance (1H NMR and13C NMR) detection data are as follows:
1H NMR(CDCl3,400MHz)δ(ppm)9.36(s,1H),8.57(m,2H),8.07(dd, 1H,J1=9.2Hz,
J2=2.0Hz), 7.75 (d, 1H, J=9.2Hz), 7.60 (t, 1H, J=7.2Hz), 7.50 (t, 2H, J=7.2Hz)13C
NMR(CDCl3,100MHz)δ(ppm)170.9,156.1, 150.5,136.6(q,JC-CF3=1.8Hz), 135.1,133.4,
129.9,129.0(q,JC-CF3=5.4Hz), 128.6,126.7,123.4,121.2 (q, JC-CF3=31.5Hz) .HRMS (ES+-
TOF)calcd for C13H9F3N3O+(M+H+):292.0692,found:292.0711.
Be prepared by embodiment 3 pyrido [1,2-a] [1,3,5]-triazine -4- ketone compound (I-3, No. CAS:
2097149-18-1) nuclear magnetic resonance (1H NMR and13C NMR) detection data are as follows:
1H NMR(CDCl3, 400MHz) and δ (ppm) 9.07 (d, 1H, J=6.8Hz), 8.48 (d, 2H, J=8.0Hz),
8.00 (t, 1H, J=8.8Hz), 7.68 (d, 1H, J=8.8Hz), 7.29 (t, 3H, J=7.2Hz), 2.44 (s, 3H)13C
NMR(CDCl3,100MHz)δ(ppm)169.6,155.5, 151.3,143.4,141.3,133.1,129.9,129.6,
129.2,125.4,117.4,21.7.HRMS (ES+-TOF)calcd for C14H12N3O+(M+H+):238.0975,found:
238.0988.
Be prepared by embodiment 4 pyrido [1,2-a] [1,3,5]-triazine -4- ketone compound (I-4, No. CAS: new
Compound) nuclear magnetic resonance (1H NMR and13C NMR) detection data are as follows:
1H NMR(CDCl3,400MHz)δ(ppm)9.09(m,1H),8.61(dd,2H,J1=6.8 Hz, J2=2.0Hz),
8.12(dd,2H,J1=6.8Hz, J2=1.6Hz), 8.07 (m, 1H), 7.73 (d, 1H, J=8.4Hz), 7.37 (td, 2H, J1
=6.8Hz, J2=1.2Hz), 3.94 (s, 3H)13C NMR (CDCl3,100MHz)δ(ppm)168.5,166.6,155.5,
151.1,141.9,139.8,133.3, 130.0,129.5,129.4,125.6,118.2,52.3.HRMS(ES+-TOF)
calcd for C15H12N3O3 +(M+H+):282.0873,found:282.0884.
Be prepared by embodiment 5 pyrido [1,2-a] [1,3,5]-triazine -4- ketone compound (I-5, No. CAS:
2097149-22-7) nuclear magnetic resonance (1H NMR and13C NMR) detection data are as follows:
1H NMR(CDCl3,400MHz)δ(ppm)9.10(dd,1H,J1=6.8Hz, J2=0.8 Hz), 8.67 (d, 2H, J
=8.4Hz), 8.08 (m, 1H), 7.73 (m, 3H), 7.39 (td, 1H, J1=6.8Hz, J2=1.2Hz)13C NMR(CDCl3,
100MHz)δ(ppm)168.1,155.5,151.1, 142.0,139.1,133.8(q,JC-CF3=32.5Hz), 130.0,
129.7,125.6,125.3(q,JC-CF3=3.6Hz), 122.5,118.3.HRMS (ES+-TOF)calcd for C13H9F3N3O+(M+H+): 292.0692,found:292.0707。
Claims (5)
1. a kind of preparation method of pyrido [1,2-a] [1,3,5]-triazine -4- ketone compound, which is characterized in that including as follows
Step: potassium peroxydisulfate, potassium permanganate, sodium azide and imidazoles [1,2- α] pyridine are added in organic solvent, are heated to
120~140 DEG C are reacted, and obtain pyrido [1,2-a] [1,3, the 5]-triazine -4- after fully reacting after post treatment
Ketone compound；
Shown in the structure such as formula (II) of described imidazoles [1,2- α] pyridine:
Shown in pyrido [1,2-a] [1,3,5]-triazine -4- ketone compound structure such as formula (I):
In formula (I)~(II), R1Selected from H, methyl, halogen, one or more of trifluoromethyl or phenyl；
R2To replace or unsubstituted phenyl, the substituent group on the phenyl be selected from trifluoromethyl, cyano ,-COOMe, methyl or
Chlorine.
2. the preparation method of pyrido [1,2-a] [1,3,5]-triazine -4- ketone compound according to claim 1, special
Sign is, with molar amount, imidazoles [1,2- α] pyridine: sodium azide: potassium peroxydisulfate: potassium permanganate=1:1~3:2~4:0.2
~1.
3. the preparation method of pyrido [1,2-a] [1,3,5]-triazine -4- ketone compound according to claim 1, special
Sign is that the time of reaction is 8~16 hours.
4. the preparation method of pyrido [1,2-a] [1,3,5]-triazine -4- ketone compound according to claim 1, special
Sign is that the organic solvent is 1,2,3- trichloropropanes.
5. the preparation method of pyrido [1,2-a] [1,3,5]-triazine -4- ketone compound according to claim 1, special
Sign is that the pyrido [1,2-a] [1,3,5]-triazine -4- ketone compound is compound shown in formula (I-1)-formula (I-5)
One of:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711063609.3A CN107880039B (en) | 2017-11-02 | 2017-11-02 | A kind of preparation method of pyrido [1,2-a] [1,3,5]-triazine -4- ketone compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711063609.3A CN107880039B (en) | 2017-11-02 | 2017-11-02 | A kind of preparation method of pyrido [1,2-a] [1,3,5]-triazine -4- ketone compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107880039A CN107880039A (en) | 2018-04-06 |
| CN107880039B true CN107880039B (en) | 2019-09-17 |
Family
ID=61783598
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711063609.3A Active CN107880039B (en) | 2017-11-02 | 2017-11-02 | A kind of preparation method of pyrido [1,2-a] [1,3,5]-triazine -4- ketone compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107880039B (en) |
-
2017
- 2017-11-02 CN CN201711063609.3A patent/CN107880039B/en active Active
Non-Patent Citations (3)
| Title |
|---|
| Oxidant-Mediated Nitrogenation and Recyclization of Imidazo [1,2-a]pyridines with Sodium Azide: Synthesis of 4H-Pyrido[1,2-a] [1,3,5]triazin-4-ones;Gangjian Cao et al.;《Adv. Synth. Catal.》;20171228;第360卷;第881–886页 |
| Synthesis and Pharmacological Activity of Triazolo[1,5-a]triazine Derivatives Inhibiting Eosinophilia;Fumihiko Akahoshi et al.;《J. Med. Chem.》;19980711;第41卷;第2985-2993页 |
| The dearomative annulation between N-2-pyridylamidine and CO2 toward pyrido[1,2-a]-1,3,5-triazin-4-ones;Minfang Xia et al.;《Org. Biomol. Chem》;20170419;第15卷;第4064–4067页 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107880039A (en) | 2018-04-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111675662B (en) | Preparation method of 2-trifluoromethyl substituted quinazolinone compound | |
| CN111978265B (en) | Preparation method of 5-trifluoromethyl substituted 1,2, 4-triazole derivative | |
| CN113105402B (en) | Preparation method of 3,4, 5-trisubstituted 1,2, 4-triazole compound | |
| CN110467579B (en) | Preparation method of 5-trifluoromethyl substituted 1,2, 4-triazole compound | |
| CN113121462B (en) | Preparation method of 5-trifluoromethyl substituted 1,2,3-triazole compound | |
| CN111704582B (en) | Preparation method of Favipiravir and derivatives thereof | |
| CN113307778A (en) | Preparation method of 3-trifluoromethyl substituted 1,2, 4-triazole compound | |
| Pletz et al. | A General and Direct Reductive Amination of Aldehydes and Ketones with Electron-Deficient Anilines | |
| CN107880039B (en) | A kind of preparation method of pyrido [1,2-a] [1,3,5]-triazine -4- ketone compound | |
| CN102127014B (en) | Azaphenanthrone compound and preparation method thereof | |
| CN110156710A (en) | A kind of polysubstituted preparation method for disliking azole compounds | |
| CN106316953A (en) | Synthetic method of 6-cyanophenanthridine compounds | |
| CN106146271B (en) | A method of diaryl ketone is prepared by aromatic yl sulphonate | |
| CN103288707B (en) | A kind of preparation method of 3-benzene sulfydryl indole derivative | |
| CN109232564A (en) | A kind of method of 3 sulfenyl substituted imidazoles of one pot process that molecular iodine promotes simultaneously [1,2-a] pyridine compounds | |
| Amos III et al. | Construction of 5, 6-ring-fused 2-pyridones: An effective annulation tactic achieved in water | |
| CN112174880A (en) | Preparation method of 1,3,4, 6-tetra-substituted pyridone derivative | |
| CN108147989B (en) | Beta-aminoketone derivative and synthetic method thereof | |
| CN105622493B (en) | Method for synthesizing fully-substituted pyridine compound through cascade reaction of enaminone and aldehyde | |
| CN114195726B (en) | Preparation method of 1,2, 4-triazole substituted arylamine compound | |
| CN106496118B (en) | A kind of quinolines enamine ketone compound and preparation method thereof | |
| CN106117081B (en) | A kind of preparation method of the alkynyl group with imine moiety of the H containing α | |
| CN102603624B (en) | Preparation method of 2-pyridine carboxamide diaryl ketone compound as well as compound | |
| CN106187899B (en) | A kind of synthetic method of fluoro azepine aromatic hydrocarbons | |
| CN113024475B (en) | Synthetic method of quinoxalinone compound |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| EE01 | Entry into force of recordation of patent licensing contract | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20180406 Assignee: ZHEJIANG HEZHONG ENVIRONMENTAL PROTECTION TECHNOLOGY CO.,LTD. Assignor: ZHEJIANG SCI-TECH University Contract record no.: X2022330000011 Denomination of invention: A preparation method of pyrido [1,2-a] [1,3,5] - triazine-4-one compound Granted publication date: 20190917 License type: Common License Record date: 20220110 Application publication date: 20180406 Assignee: Shaoxing Xinfeng New Material Technology Co.,Ltd. Assignor: ZHEJIANG SCI-TECH University Contract record no.: X2022330000010 Denomination of invention: A preparation method of pyrido [1,2-a] [1,3,5] - triazine-4-one compound Granted publication date: 20190917 License type: Common License Record date: 20220110 Application publication date: 20180406 Assignee: Zhejiang pulangsi Chemical Co.,Ltd. Assignor: ZHEJIANG SCI-TECH University Contract record no.: X2022330000009 Denomination of invention: A preparation method of pyrido [1,2-a] [1,3,5] - triazine-4-one compound Granted publication date: 20190917 License type: Common License Record date: 20220110 |
|
| EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20180406 Assignee: Huachen essence (Yiwu) Co.,Ltd. Assignor: ZHEJIANG SCI-TECH University Contract record no.: X2022330000075 Denomination of invention: A preparation method of pyrido [1,2-a] [1,3,5] - triazine-4-one compound Granted publication date: 20190917 License type: Common License Record date: 20220428 |
|
| EE01 | Entry into force of recordation of patent licensing contract | ||
| EE01 | Entry into force of recordation of patent licensing contract | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20180406 Assignee: JIAXING SYNBIOLAB BIOTECHNOLOGY CO.,LTD. Assignor: ZHEJIANG SCI-TECH University Contract record no.: X2023980032642 Denomination of invention: A preparation method of pyridino [1,2-a] [1,3,5] - triazine-4-one compound Granted publication date: 20190917 License type: Common License Record date: 20230224 Application publication date: 20180406 Assignee: Jiaxing zhuo'an Biotechnology Co.,Ltd. Assignor: ZHEJIANG SCI-TECH University Contract record no.: X2023980032725 Denomination of invention: A preparation method of pyridino [1,2-a] [1,3,5] - triazine-4-one compound Granted publication date: 20190917 License type: Common License Record date: 20230224 |
|
| EE01 | Entry into force of recordation of patent licensing contract | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20180406 Assignee: Jiaxing yilaibo Pharmaceutical Technology Co.,Ltd. Assignor: ZHEJIANG SCI-TECH University Contract record no.: X2023980032952 Denomination of invention: A preparation method of pyridino [1,2-a] [1,3,5] - triazine-4-one compound Granted publication date: 20190917 License type: Common License Record date: 20230228 |
|
| EE01 | Entry into force of recordation of patent licensing contract | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20180406 Assignee: Jiaxing Lingxian New Material Technology Co.,Ltd. Assignor: ZHEJIANG SCI-TECH University Contract record no.: X2023330000082 Denomination of invention: Preparation method of a pyridino [1,2-a] [1,3,5] - triazine-4-one compound Granted publication date: 20190917 License type: Common License Record date: 20230310 |
|
| EE01 | Entry into force of recordation of patent licensing contract | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20180406 Assignee: ZHEJIANG EXPO NEW MATERIALS CO.,LTD. Assignor: ZHEJIANG SCI-TECH University Contract record no.: X2023330000821 Denomination of invention: Preparation method of a pyridino [1,2-a] [1,3,5] - triazine-4-one compound Granted publication date: 20190917 License type: Common License Record date: 20231107 |