CN110407761A - A kind of polysubstituted heterocyclic nitrogen compound and the preparation method and application thereof - Google Patents
A kind of polysubstituted heterocyclic nitrogen compound and the preparation method and application thereof Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—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
- C07D405/06—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 linked by a carbon chain containing only aliphatic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—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
- C07D409/06—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 linked by a carbon chain containing only aliphatic carbon atoms
Abstract
One kind polysubstituted heterocyclic nitrogen compound as shown in formula (III), preparation method are as follows: by compound shown in formula (I), compound shown in formula (II), metallic catalyst, alkaline matter, organic solvent mixing, 5~30h is stirred to react at 80~140 DEG C, reaction solution is post-treated later, obtain product shown in formula (III), compound (III) can be applied to the Striazine derivative that synthesis has antibacterial and anti-tumor biological, the present invention develops polysubstituted heterocyclic nitrogen compound and the preparation method and application thereof, preparation process reaction condition of the present invention is mild, raw material is easy to get, it is easy to operate, it is at low cost, there is preferable prospects for commercial application；
Description
(1) technical field
The present invention relates to a kind of polysubstituted heterocyclic nitrogen compounds and the preparation method and application thereof.
(2) background technique
Heterocyclic nitrogen compound is a kind of weight as a variety of biologically active natural products and the basic framework of drug
The organic synthesis intermediate wanted, while studying and finding that such compound has the multiple biological activities such as anticancer, antimalarial, weeding, quilt
It is widely used in the fields such as medicine, pesticide.Therefore, studying heterocyclic nitrogen compound and preparation method thereof, there is important reality to answer
With value.
(3) summary of the invention
The purpose of the present invention is to provide a kind of polysubstituted heterocyclic nitrogen compounds and the preparation method and application thereof.
Technical scheme is as follows:
One kind polysubstituted heterocyclic nitrogen compound as shown in formula (III):
In formula (III),
R1For hydrogen or C8~C15 aralkyl, preferably hydrogen or benzyl；
R2For hydrogen or C1~C4 alkyl, preferably hydrogen or methyl；
R3、R4Respectively stand alone as C1~C10 alkyl or R3、R4N between the two combines to be formed containing N or containing N, O
C4~C8 heterocycle；It is preferred that R3、R4Respectively stand alone as methyl or R3、R4N between the two combines to form piperidine ring or morpholine
Ring；
R5For sulfur-bearing heteroaromatic, C5~C10 aryl or the C5~C10 aryl being substituted by one or more substituents, institute
Stating substituent group is C1~C4 alkyl, C1~C4 alkoxy or halogen；It is preferred that R5Replace for thiophene, phenyl or by one or two
The phenyl that base replaces, the substituent group are methyl, methoxyl group, 3,4- methylene dimethoxy or chlorine.
The polysubstituted heterocyclic nitrogen compound of the present invention as shown in formula (III) the preparation method comprises the following steps:
Compound shown in compound shown in formula (I), formula (II), metallic catalyst, alkaline matter, organic solvent are mixed,
5~30h (preferably 12~for 24 hours) are stirred to react under 80~140 DEG C (preferably 120~140 DEG C), reaction solution is post-treated later,
Obtain product shown in formula (III)；
Compound shown in the formula (I), compound, metallic catalyst shown in formula (II), alkaline matter substance amount it
Than for 1:0.5~6:0.01~0.05:1~3, preferably 1:2~6:0.01~0.03:1~2；
The volumetric usage of the organic solvent is calculated as 5~20mL/mmol with the amount of the substance of compound shown in formula (I)；
The metallic catalyst is ruthenium catalyst, such as: three (triphenylphosphine) ruthenous chlorides, two (triphenylphosphine) rings penta 2
Alkene ruthenic chloride or dichloro (p -Methylisopropylbenzene base) ruthenium dimer；It is preferred that three (triphenylphosphine) ruthenous chlorides；
The alkaline matter is organic base, preferably potassium tert-butoxide；
The organic solvent is ethers, preferably Isosorbide-5-Nitrae-dioxane, tetrahydrofuran or 2- methyltetrahydrofuran；
The method of the post-processing are as follows: after reaction, be cooled to room temperature (20~30 DEG C) to reaction solution, methanol is added
(solubilized target product), filtering carry out column chromatography for separation after taking filtrate to be concentrated, with ethyl acetate/petroleum ether volume ratio 1:10's
Mixed liquor is eluant, eluent, collects the eluent containing target compound, solvent and drying is evaporated off, obtains product shown in formula (III)；
In formula (I) or (II), R1、R2、R3、R4、R5Definition it is identical with formula (III).
The polysubstituted heterocyclic nitrogen compound (III) of the present invention is under palladium carbon and hydrogen effect, can be with by debenzylation
Synthesize Striazine derivative (IV) (the relevant biological activity number of Striazine derivative with antibacterial and the bioactivity such as antitumor
According to can be found in Org.Biomol.Chem., 2018,16,6140-6145, CN201810701310.4, CN201810701309.1,
CN201810700670.2), thus the polysubstituted heterocyclic nitrogen compound (III) of the present invention can be used as it is a variety of biologically active
The important intermediate of substance, has a wide range of applications.
In formula (IV), R3、R4、R5Definition it is identical with formula (III).
The beneficial effects of the present invention are: the present invention develops polysubstituted heterocyclic nitrogen compound and preparation method thereof and answers
With, preparation process reaction condition of the present invention is mild, and raw material is easy to get, and it is easy to operate, it is at low cost, before having preferable industrial application
Scape.
(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 the reaction vessel plus N2Benzyl-N4,N4, 6- trimethyl -1,3,5-triazines (I) (60.3mg, 0.250mmol),
Benzylalcohol (108.2mg, 1.00mmol), three (triphenylphosphine) ruthenous chlorides (4.9mg, 0.005mmol), potassium tert-butoxide (28.8mg,
0.25mmol), it mixes in Isosorbide-5-Nitrae-dioxane (2mL), is stirred to react 22 hours in 140 DEG C of oil baths；After reaction, add first
Filtrate is concentrated in alcohol, filtering, and column chromatographs (ethyl acetate: petroleum ether=1:10), collects RfThe eluent of value 0.3~0.35, decompression
Distillation, is dried to obtain target compound (III-1), 74.8mg, yield 91%.
1H NMR(500MHz,CDCl3)δ7.37-7.30(m,4H),7.30-7.24(m,5H),7.23-7.17(m,1H),
5.70 (br, 1H), 4.64 (d, J=5.0Hz, 1H), 3.19 (s, 3H), 3.13 (s, 3H), 3.11-3.02 (m, 2H), 2.98-
2.74(m,2H)。
Embodiment 2:
Temperature is reduced to 80 DEG C, other operations obtain product 3mg, yield 4% with embodiment 1.
Embodiment 3:
30h will be extended to the time, Isosorbide-5-Nitrae-dioxane is changed to 1.2mL, other operations obtain product with embodiment 1
53.4mg, yield 64%.
Embodiment 4:
Time 5h will be foreshortened to, with embodiment 1,25.1mg, obtaining product yield is 31% for other operations.
Embodiment 5:
The amount of benzylalcohol is changed to (166.4mg, 1.5mmol), other operations obtain product 65.1mg, yield with embodiment 1
It is 80%.
Embodiment 6:
The amount of benzylalcohol is changed to (13.9mg, 0.13mmol), other operations obtain product 7.3mg, yield with embodiment 1
It is 9%.
Embodiment 7:
The amount of ruthenium catalyst is changed to (2.6mg, 0.0025mmol), other operations obtain product with embodiment 1
54.7mg, yield 66%.
Embodiment 8:
The amount of ruthenium catalyst is changed to (11.3mg, 0.012mmol), Isosorbide-5-Nitrae-dioxane is changed to 5mL, and other are operated with real
Example 1 is applied, product 64.9mg, yield 78% are obtained.
Embodiment 9:
Three (triphenylphosphine) ruthenous chlorides are changed to ruthenic oxide (1.5mg, 0.005mmol), other operate same embodiment
1, reaction does not obtain target product.
Embodiment 10:
Three (triphenylphosphine) ruthenous chlorides are changed to ten dicarbapentaborane rutheniums (3.5mg, 0.005mmol), other operations are the same as implementation
Example 1, reaction do not obtain target product.
Embodiment 11:
Three (triphenylphosphine) ruthenous chlorides are changed to 1,5- cyclo-octadiene ruthenous chloride (1.5mg, 0.005mmol), other
Operation does not obtain target product with embodiment 1, reaction.
Embodiment 12:
Three (triphenylphosphine) ruthenous chlorides are changed to ruthenium trichloride (1.2mg, 0.005mmol), other operate same embodiment
1, reaction does not obtain target product.
Embodiment 13:
By three (triphenylphosphine) ruthenous chlorides be changed to bis- (4- isopropyl methyl phenyl) the ruthenium dimers of dichloro (6.6mg,
0.005mmol), other operations obtain product 28.3mg, yield 34% with embodiment 1.
Embodiment 14:
By potassium tert-butoxide (86.4mg, 0.75mmol), other operations obtain product 27.5mg, yield is with embodiment 1
33%.
Embodiment 15: the preparation of compound (III-2)
Benzylalcohol is only changed into xylyl alcohol (91.0mg, 0.75mmol) with embodiment 1, target chemical combination is made by operation
Object (III-2), 84.9mg, yield 98%.
1H NMR(500MHz,CDCl3) δ 7.38-7.31 (m, 4H), 7.30-7.25 (m, 1H), 7.17 (d, J=8.0Hz,
2H), 7.10 (d, J=8.0Hz, 2H), 5.48 (br, 1H), 4.63 (d, J=4.9Hz, 1H), 3.19 (s, 3H), 3.13 (s,
3H), 3.04 (t, J=6.9,2H), 2.90-2.68 (m, 2H), 2.33 (s, 3H).
Embodiment 16: the preparation of compound (III-3)
Operation only changes benzylalcohol into 4- chlorobenzyl alcohol (106.8mg, 0.75mmol) with embodiment 1, and target compound is made
(III-3), 86.5mg, yield 95%.
1H NMR(500MHz,CDCl3) δ 7.34-7.30 (m4H), 7.30-7.26 (m, 1H), 7.23 (d, J=8.2Hz,
2H), 7.17 (d, J=8.2Hz, 2H), 5.50 (br, 1H), 4.62 (d, J=5.4Hz, 2H), 3.16 (s, 3H), 3.13 (s,
3H), 3.04 (t, J=7.2Hz, 2H), 2.92-2.64 (m, 2H).
Embodiment 17: the preparation of compound (III-4)
Operation only changes benzylalcohol into 4- methoxyl group benzylalcohol (75.2mg, 0.51mmol) with embodiment 1, and targeted is made
It closes object (III-4), 78.0mg, yield 86%.
1H NMR(600MHz,CDCl3) δ 7.38-7.30 (m, 4H), 7.28-7.21 (m, 1H), 7.17 (d, J=8.5Hz,
2H), 6.81 (d, J=8.5Hz, 2H), 5.35 (br, 1H), 4.62 (d, J=4.0Hz, 2H), 3.78 (s, 3H), 3.16 (s,
3H), 3.11 (s, 3H), 2.99 (t, J=7.9Hz, 2H), 2.83-2.65 (m, 2H).
Embodiment 18: the preparation of compound (III-5)
Operation only changes benzylalcohol into 2- methoxyl group benzylalcohol (103.1mg, 0.75mmol) with embodiment 1, and targeted is made
It closes object (III-5), 87.5mg, yield 95%.
1H NMR(600MHz,CDCl3) δ 7.36-7.30 (m, 4H), 7.26-7.24 (m, 1H), 7.19 (d, J=7.8Hz,
1H), 7.16 (t, J=7.8Hz, 1H), 6.87 (t, J=7.8Hz, 1H), 6.84 (d, J=7.8Hz, 1H), 5.35 (br, 1H),
4.62 (d, J=4.2Hz, 2H), 3.82 (s, 3H), 3.16 (s, 3H), 3.12 (s, 3H), 3.07-3.03 (m, 2H), 2.86-
2.70(m,2H)。
Embodiment 19: the preparation of compound (III-6)
Operation only changes benzylalcohol into 3- methoxyl group benzylalcohol (75.1mg, 0.50mmol) with embodiment 1, and targeted is made
It closes object (III-6), 60.2mg, yield 66%.
1H NMR(500MHz,CDCl3) δ 7.40-7.30 (m, 4H), 7.29-7.25 (m, 1H), 7.20 (t, J=7.9Hz,
1H), 6.87 (d, J=7.9Hz, 1H), 6.83 (t, J=2.2Hz, 1H), 6.75 (dd, J=7.9,2.2Hz, 1H), 5.46 (br,
1H), 4.63 (d, J=5.1Hz, 2H), 3.80 (s, 3H), 3.18 (s, 3H), 3.14 (s, 3H), 3.06 (t, J=7.2Hz, 2H),
2.90-2.70(m,2H)。
Embodiment 20: the preparation of compound (III-7)
Operation only changes benzylalcohol into 3- chlorobenzene methanol (72.2mg, 0.50mmol) with embodiment 1, and target chemical combination is made
Object (III-7), 53.1mg, yield 58%.
1H NMR(500MHz,CDCl3) δ 7.37-7.30 (m, 4H), 7.30-7.25 (m, 2H), 7.20 (t, J=7.5Hz,
1H), 7.16 (dt, J=7.5,1.5Hz, 1H), 7.13 (d, J=7.5,1H), 5.50 (br, 1H), 4.63 (d, J=5.6Hz,
2H), 3.16 (s, 3H), 3.13 (s, 3H), 3.06 (t, J=7.6Hz, 2H), 2.89-2.71 (m, 2H).
Embodiment 21: the preparation of compound (III-8)
Operation only changes benzylalcohol into 3- methylbenzyl alcohol (92.0mg, 0.75mmol) with embodiment 1, and targeted is made
It closes object (III-8), 74.3mg, yield 85%.
1H NMR(500MHz,CDCl3) δ 7.35-7.28 (m, 4H), 7.27-7.22 (m, 1H), 7.15 (t, J=7.5Hz,
1H), 7.08 (s, 1H), 7.05 (d, J=7.5Hz, 1H), 6.99 (d, J=7.5Hz, 1H), 5.49 (br, 1H), 4.61 (d, J=
5.1Hz, 2H), 3.15 (s, 3H), 3.11 (s, 3H), 3.01 (t, J=7.2,2H), 2.90-2.71 (m, 2H), 2.31 (s, 3H).
Embodiment 22: the preparation of compound (III-9)
Operation only changes benzylalcohol into the sub- methoxy benzyl alcohol (114.8mg, 0.75mmol) of 3,4- bis-, system with embodiment 1
It obtains target compound (III-9), 85.0mg, yield 90%.
1H NMR(500MHz,CDCl3) δ 7.37-7.30 (m, 4H), 7.30-7.25 (m, 1H), 6.77 (d, J=1.2Hz,
1H), 6.73 (d, J=7.9Hz, 1H), 6.70 (dd, J=7.9,1.2Hz, 1H), 5.92 (s, 2H), 5.58 (br, 1H), 4.63
(d, J=5.4Hz, 2H), 3.16 (s, 3H), 3.14 (s, 3H), 3.00 (t, J=7.3,2H), 2.87-2.69 (m, 2H).
Embodiment 23: the preparation of compound (III-10)
Operation only changes benzylalcohol into 2,3- 3,5-dimethoxybenzoic alcohol (126.8mg, 1.00mmol) with embodiment 1, is made
Target compound (III-10), 72.6mg, yield 74%.
1H NMR(600MHz,CDCl3) δ 7.36-7.29 (m, 4H), 7.26-7.24 (m, 1H), 6.96 (t, J=7.9Hz,
1H), 6.84 (d, J=7.9Hz, 1H), 6.77 (dd, J=7.9,1.0Hz, 1H), 5.36 (br, 1H), 4.62 (d, J=4.8Hz,
2H),3.85(s,3H),3.84(s,2H),3.15(s,3H),3.10-2.97(m,5H),2.87-2.73(m,2H)。
Embodiment 24: the preparation of compound (III-11)
Operation only changes benzylalcohol into 2- thenyl alcohol (86.0mg, 0.75mmol) with embodiment 1, and target chemical combination is made
Object (III-11), 51.5mg, yield 61%.
1H NMR(600MHz,CDCl3) δ 7.40-7.29 (m, 4H), 7.27-7.20 (m, 1H), 7.09 (dd, J=4.9,
0.8Hz, 1H), 6.90 (dd, J=4.9,3.6Hz, 1H), 6.83 (dd, J=3.6,0.8Hz, 1H), 5.56 (br, 1H), 4.67-
4.54(m,2H),3.35-3.25(m,2H),3.17(s,3H),3.12(s,3H),295-2.79(s,2H)。
Embodiment 25: the preparation of compound (III-12)
Operation is with embodiment 1, only by N2Benzyl-N4,N4, 6- trimethyl -1,3,5- triazine changes N into2Benzyl -4- first
Base -6- piperidines -1,3,5-triazines (71.5mg, 0.25mmol), is made target compound (III-12), 76.4mg, and yield is
81%.
1H NMR(500MHz,CDCl3) δ 7.38-7.31 (m, 4H), 7.30-7.25 (m, 5H), 7.19 (td, J=6.0,
2.7Hz, 1H), 5.38 (br, 1H), 4.78-4.54 (m, 2H), 3.89-3.70 (m, 4H), 3.07 (t, J=7.5,2H), 2.94-
2.74(m,2H),1.69-1.64(m,2H),1.61-1.52(m,4H)。
Embodiment 26: the preparation of compound (III-13)
Operation is with embodiment 1, only by N2Benzyl-N4,N4, 6- trimethyl -1,3,5- triazine changes N into2Benzyl -4- first
Base -6- morpholine -1,3,5-triazines (70.2mg, 0.25mmol), is made target compound (III-13), 81.8mg, and yield is
87%.
1H NMR(500MHz,CDCl3)δ7.37-7.32(m,4H),7.30-7.28(m,3H),7.26-7.24(m,2H),
7.23-7.18(m,1H),5.89(br,1H),4.72-4.53(m,2H),3.89-3.74(m,4H),3.74-3.54(m,4H),
3.10-3.00(m,2H),2.93-2.67(m,2H)。
Embodiment 27: the preparation of compound (III-14)
Operation is with embodiment 1, only by N2Benzyl-N4,N4, 6- trimethyl -1,3,5- triazine changes N into2,N2Dibenzyl-
N4,N4, 6- trimethyl -1,3,5-triazines (80.1mg, 0.25mmol), obtained target compound (III-14), 64.7mg, yield
It is 64%.
1H NMR(500MHz,CDCl3)δ7.41-7.24(m,14H),7.22-7.17(m,1H),4.87(s,2H),4.79
(s,2H),3.21(s,3H),3.16-3.00(m,5H),2.98-2.84(m,2H)。
Embodiment 28: the preparation of compound (III-15)
Operation is with embodiment 1, only by N2Benzyl-N4,N4, 6- trimethyl -1,3,5- triazine changes N into2To methyl benzyl
Base-N4,N4, 6- trimethyl -1,3,5-triazines (64.3mg, 0.25mmol), obtained target compound (II -15), 69.2mg, receipts
Rate is 83%.
1H NMR(500MHz,CDCl3) δ 7.22 (d, J=7.7Hz, 2H), 7.15 (d, J=7.8Hz, 2H), 7.13 (d, J
=7.8Hz, 2H), 7.08 (d, J=7.7Hz, 2H), 5.56-5.23 (m, 1H), 4.57 (d, J=4.6Hz, 2H), 3.15 (s,
3H),3.14(s,3H),3.06-2.95(m,2H),2.86-2.69(m,2H),2.34(s,3H),2.31(s,3H)。
Embodiment 29: compound (IV)
1 gained compound (III) (1mmol) of embodiment and 10% palladium carbon (300mg) are added in 10mL methanol, in hydrogen
Under the conditions of back flow reaction be down to room temperature until the reaction is complete, filter, concentration, target compound is obtained by column chromatography for separation
(IV)。
Claims (10)
1. a kind of polysubstituted heterocyclic nitrogen compound as shown in formula (III):
In formula (III),
R1For hydrogen or C8~C15 aralkyl；
R2For hydrogen or C1~C4 alkyl；
R3、R4Respectively stand alone as C1~C10 alkyl or R3、R4N between the two combines to be formed containing N or containing C4~C8 of N, O
Heterocycle；
R5For sulfur-bearing heteroaromatic, C5~C10 aryl or the C5~C10 aryl being substituted by one or more substituents, the substitution
Base is C1~C4 alkyl, C1~C4 alkoxy or halogen.
2. the preparation method of polysubstituted heterocyclic nitrogen compound shown in formula (III) as described in claim 1, which is characterized in that
The preparation method is that:
Compound shown in compound shown in formula (I), formula (II), metallic catalyst, alkaline matter, organic solvent are mixed, 80
5~30h is stirred to react at~140 DEG C, reaction solution is post-treated later, obtains product shown in formula (III)；
The ratio between compound shown in the formula (I), compound, metallic catalyst, the amount of substance of alkaline matter shown in formula (II) are
1:0.5~6:0.01~0.05:1~3；
The metallic catalyst is ruthenium catalyst；
The alkaline matter is organic base；
The organic solvent is ethers；
In formula (I) or (II), R1、R2、R3、R4、R5Definition it is identical with formula (III).
3. preparation method as claimed in claim 2, which is characterized in that reaction temperature is 120~140 DEG C.
4. preparation method as claimed in claim 2, which is characterized in that the reaction time be 12~for 24 hours.
5. preparation method as claimed in claim 2, which is characterized in that compound shown in the formula (I), chemical combination shown in formula (II)
The ratio between amount of substance of object, metallic catalyst, alkaline matter is 1: 2~6: 0.01~0.03: 1~2.
6. preparation method as claimed in claim 2, which is characterized in that the volumetric usage of the organic solvent is shown in formula (I)
The amount of the substance of compound is calculated as 5~20mL/mmol.
7. preparation method as claimed in claim 2, which is characterized in that the metallic catalyst is three (triphenylphosphine) dichlorides
Ruthenium, two (triphenylphosphine) cyclopentadiene ruthenic chlorides or dichloro (p -Methylisopropylbenzene base) ruthenium dimer.
8. preparation method as claimed in claim 2, which is characterized in that the alkaline matter is potassium tert-butoxide.
9. preparation method as claimed in claim 2, which is characterized in that the organic solvent is Isosorbide-5-Nitrae-dioxane, tetrahydro furan
It mutters or 2- methyltetrahydrofuran.
10. polysubstituted heterocyclic nitrogen compound shown in formula (III) as described in claim 1 has antibacterial and antitumor in synthesis
Application in the Striazine derivative (IV) of bioactivity, the synthetic method are as follows: polysubstituted heterocyclic nitrogen compound (III)
Under palladium carbon and hydrogen effect, by debenzylation, Striazine derivative (IV) is obtained；
In formula (IV), R3、R4、R5Definition it is identical with formula (III).
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| CN112159360A (en) * | 2020-09-15 | 2021-01-01 | 浙江工业大学 | Preparation method of 2-dimethylamino-6-benzylamino substituted triazine compound |
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| CN112159360A (en) * | 2020-09-15 | 2021-01-01 | 浙江工业大学 | Preparation method of 2-dimethylamino-6-benzylamino substituted triazine compound |
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