CN103613595B - A kind of preparation method of amide urea type compound - Google Patents
A kind of preparation method of amide urea type compound Download PDFInfo
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- CN103613595B CN103613595B CN201310673028.7A CN201310673028A CN103613595B CN 103613595 B CN103613595 B CN 103613595B CN 201310673028 A CN201310673028 A CN 201310673028A CN 103613595 B CN103613595 B CN 103613595B
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- -1 amide urea type compound Chemical class 0.000 title claims abstract description 26
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 38
- 238000006243 chemical reaction Methods 0.000 claims abstract description 33
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 claims abstract description 19
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims abstract description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims abstract description 15
- 150000002148 esters Chemical class 0.000 claims abstract description 10
- 230000035484 reaction time Effects 0.000 claims abstract description 6
- 150000001408 amides Chemical class 0.000 claims abstract description 4
- 238000001914 filtration Methods 0.000 claims abstract description 4
- 150000003672 ureas Chemical class 0.000 claims abstract description 4
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 3
- 230000005855 radiation Effects 0.000 claims abstract description 3
- 150000003852 triazoles Chemical class 0.000 claims abstract description 3
- 239000012948 isocyanate Substances 0.000 claims description 6
- 150000002513 isocyanates Chemical class 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- SUVCZZADQDCIEQ-UHFFFAOYSA-N 1-isocyanato-2-methoxybenzene Chemical compound COC1=CC=CC=C1N=C=O SUVCZZADQDCIEQ-UHFFFAOYSA-N 0.000 claims description 5
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 claims description 4
- XEFUJGURFLOFAN-UHFFFAOYSA-N 1,3-dichloro-5-isocyanatobenzene Chemical compound ClC1=CC(Cl)=CC(N=C=O)=C1 XEFUJGURFLOFAN-UHFFFAOYSA-N 0.000 claims description 3
- WSXXIRCUOWOHKI-UHFFFAOYSA-N 1,4-dichloro-2-isocyanato-5-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC(Cl)=C(C=C1Cl)N=C=O WSXXIRCUOWOHKI-UHFFFAOYSA-N 0.000 claims description 3
- NGQMCUWZGVMILT-UHFFFAOYSA-N 1-chloro-3-isocyanato-2-methylbenzene Chemical compound CC1=C(Cl)C=CC=C1N=C=O NGQMCUWZGVMILT-UHFFFAOYSA-N 0.000 claims description 3
- FZCFUPBIPMLIPI-UHFFFAOYSA-N 1-isocyanato-2-methyl-4-nitrobenzene Chemical compound CC1=CC([N+]([O-])=O)=CC=C1N=C=O FZCFUPBIPMLIPI-UHFFFAOYSA-N 0.000 claims description 3
- CPPGZWWUPFWALU-UHFFFAOYSA-N 1-isocyanato-3-methylbenzene Chemical compound CC1=CC=CC(N=C=O)=C1 CPPGZWWUPFWALU-UHFFFAOYSA-N 0.000 claims description 3
- BDQNKCYCTYYMAA-UHFFFAOYSA-N 1-isocyanatonaphthalene Chemical compound C1=CC=C2C(N=C=O)=CC=CC2=C1 BDQNKCYCTYYMAA-UHFFFAOYSA-N 0.000 claims description 3
- DVFVNJHIVAPTMS-UHFFFAOYSA-N 1-methyl-2-(trifluoromethyl)benzene Chemical compound CC1=CC=CC=C1C(F)(F)F DVFVNJHIVAPTMS-UHFFFAOYSA-N 0.000 claims description 3
- KNHJIEOCVVIBIV-UHFFFAOYSA-N 2,3-dimethylphenyl isocyanate Chemical compound CC1=CC=CC(N=C=O)=C1C KNHJIEOCVVIBIV-UHFFFAOYSA-N 0.000 claims description 3
- SOXVXJQIQVOCAY-UHFFFAOYSA-N 2,5-dimethylphenyl isocyanate Chemical compound CC1=CC=C(C)C(N=C=O)=C1 SOXVXJQIQVOCAY-UHFFFAOYSA-N 0.000 claims description 3
- QULYNCCPRWKEMF-UHFFFAOYSA-N parachlorobenzotrifluoride Chemical compound FC(F)(F)C1=CC=C(Cl)C=C1 QULYNCCPRWKEMF-UHFFFAOYSA-N 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 abstract 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 26
- 238000003756 stirring Methods 0.000 description 15
- 238000005160 1H NMR spectroscopy Methods 0.000 description 14
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 14
- 230000015572 biosynthetic process Effects 0.000 description 14
- 239000013078 crystal Substances 0.000 description 14
- 238000003786 synthesis reaction Methods 0.000 description 14
- 238000002604 ultrasonography Methods 0.000 description 14
- 239000004202 carbamide Substances 0.000 description 8
- 235000013877 carbamide Nutrition 0.000 description 8
- 125000003368 amide group Chemical group 0.000 description 4
- 239000000047 product Substances 0.000 description 3
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- LUBJCRLGQSPQNN-UHFFFAOYSA-N Z-phenylurea Natural products NC(=O)NC1=CC=CC=C1 LUBJCRLGQSPQNN-UHFFFAOYSA-N 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- OFLXLNCGODUUOT-UHFFFAOYSA-N acetohydrazide Chemical compound C\C(O)=N\N OFLXLNCGODUUOT-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 150000004866 oxadiazoles Chemical class 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 230000002194 synthesizing 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of preparation method of amide urea derivative as shown in the formula (I), comprise the steps: the 8-chloro-[1 as shown in formula II, 2,4] triazole [4,3-a] pyridine hydrazides carries out Ultrasonic Radiation reaction in 25 DEG C with isocyanic ester as shown in formula III in acetonitrile, fully namely obtains product amide base urea derivatives through filtration treatment after reaction.In formula (I) or formula (III), wherein R represents phenyl, 2,5-3,5-dimethylphenyl, 2-p-methoxy-phenyl, 2-methyl-3-chloro-phenyl-, isophthalic p-methoxy-phenyl, 3-aminomethyl phenyl, 2,5-dichlor-4-trifluoromethyl phenyl, 3,5-dichlorophenyl, 2,3-3,5-dimethylphenyls, 2-methyl-4-nitrophenyl, 2-methyl-3-trifluoromethyl, 2-Trifluoromethoxyphen-l, naphthyl, the chloro-5-trifluoromethyl of 2-.Preparation method of the present invention is simple to operate, and product yield is higher, the reaction times is short, reagent used in reaction process is all less expensive, has good using value.
Description
(1)
technical field
The present invention relates to a kind of preparation method of amide urea type compound.
(2)
background technology
Carbamide compounds be a class important there is bioactive material, due to it be easy to preparation, correlated response is more, itself and had been widely used as the organic compound tool of Intermediate Preparation by him.Domestic and international scientist conducts in-depth research it.
At present, the method for synthesizing amide base urea mainly contains as follows:
JournaloforganicChemistry magazine ran phenyl isocyanate and acethydrazide at room temperature stir 18 hours, obtain amide group urea.
BashkirskiiKhimicheskiiZhurnal magazine ran prepares amide group urea by phenyl amino carbamide compound and chloroformic acid derivatives reaction.
Tr.Ural'sk.Un-tov.Organ.Khimiya magazine ran to be reacted by phenyl amino carbamide compound and carboxylates derivatives and prepares amide group urea.
JournalofHeterocyclicChemistry magazine ran prepares amide group urea by aniline and oxadiazoles reactive ketone.
(3) summary of the invention
The technical problem to be solved in the present invention is to provide a kind of method of simple preparation amide urea derivative.
For solving the problems of the technologies described above, the present invention adopts following technical scheme:
A kind of preparation method of amide urea derivative as shown in the formula (I), comprise the steps: 8-chloro-[1 as shown in equation, 2,4] triazole [4,3-a] pyridine hydrazides (II) carries out Ultrasonic Radiation reaction in 25 DEG C with isocyanic ester as shown in formula III in acetonitrile, and fully after reaction, gained reaction solution processes and obtains product amide base urea derivatives after filtration.
Reaction equation is as follows:
In formula (I) or formula (III), wherein R represents substituted-phenyl and naphthyl; The phenyl ring of described substituted-phenyl is monosubstituted or polysubstituted, described substituting group is selected from following groups: methyl, trifluoromethyl, nitro, phenoxy group, trifluoromethoxy, methoxyl group, halogen, hydrogen.
Further, described isocyanic ester is preferably one of following: phenyl isocyanate, 2, 5-dimethylphenyl isocyanate, 2-methoxyphenyl isocyanate, 2-methyl-3-chlorophenyl isocyanate, isophthalic methoxyphenyl isocyanate, 3-methylphenyl isocyanate, 2, 5-dichlor-4-trifluoromethyl phenyl isocyanate, 3, 5-dichlorophenyl isocyanate, 2, 3-dimethylphenyl isocyanate, 2-methyl-4-nitrophenyl isocyanate, 2-methyl-3-trifluoromethylbenzene based isocyanate, 2-Trifluoromethoxyphen-l isocyanic ester, naphthyl isocyanate, 2-chloro-5-trifluoromethylbenzene based isocyanate.
Further, in the present invention, described 8-chloro-[1,2,4] triazole [4,3-a] pyridine hydrazides: isocyanic ester: the molar ratio of acetonitrile is preferably 1:1.0 ~ 1.5:2 ~ 20.
Further, described temperature of reaction is preferably 0-60 DEG C, and the reaction times is preferably 1-15min.
Further, described temperature of reaction is preferably 25 DEG C, and the reaction times is preferably 3min.
The reaction solution that the present invention fully reacts rear gained can obtain target product through simple conventional aftertreatment, and described post-treating method can be: reaction terminates, and reaction solution direct filtration is obtained solid product.Compared with prior art, beneficial effect of the present invention is: preparation method of the present invention, post-treating method are simple to operate, and product yield is higher, the reaction times is short, reagent used in reaction process is all less expensive, has good using value.
(4) embodiment
Below in conjunction with embodiment, technical scheme of the present invention is described further, but protection scope of the present invention is not limited to this.
The synthesis of embodiment 1N-(8-chloro-[1,2,4] triazolo [4,3-a] pyridine-3-amide group)-N-phenylurea
8-chloro-[1,2,4] triazole [4,3-a] pyridine hydrazides (20mmol) and phenyl isocyanate (24mmol), in ultrasound reactor, stir.3min is reacted at 25 DEG C.Reaction terminates, and filters to obtain white crystal, i.e. embodiment 1.Fusing point > 300
?c, yield is 55%.
1HNMR(CDCl
3,400MHz):6.97(d,
J=7.6Hz,1H,Ph-H),7.26(m,5H,1Py-H,4Ph-H),7.90(d,
J=7.6Hz,1H,Py-H),8.43(s,1H,NH),8.80(s,1H,NH),9.14(d,
J=7.2Hz,1H,Py-H),10.99(s,1H,NH).
The synthesis of embodiment 2N-(8-chloro-[1,2,4] triazolo [4,3-a] pyridine-3-amide group)-N-2,5-3,5-dimethylphenyl urea
8-chloro-[1,2,4] triazole [4,3-a] pyridine hydrazides (20mmol) and 2,5-dimethylphenyl isocyanate (24mmol), in ultrasound reactor, stir.3min is reacted at 25 DEG C.Reaction terminates, and filters to obtain light yellow crystal, i.e. embodiment 2.Fusing point > 300 C, yield is 80%.
1HNMR(CDCl
3,400MHz):2.18(s,3H,CH
3),2.24(s,3H,CH
3),6.80(d,
J=7.6Hz,1H,Ph-H),7.05(d,
J=7.6Hz,1H,Ph-H),7.25(t,
J=7.2Hz,1H,Py-H),7.50(s,1H,Ph-H),7.83(d,
J=7.6Hz,1H,Py-H),8.06(s,1H,NH),8.57(s,1H,NH),9.14(d,
J=7.2Hz,1H,Py-H),11.02(s,1H,NH).
The synthesis of embodiment 3N-(8-chloro-[1,2,4] triazolo [4,3-a] pyridine-3-amide group)-N-2-p-methoxy-phenyl urea
8-chloro-[1,2,4] triazole [4,3-a] pyridine hydrazides (20mmol) and 2-methoxyphenyl isocyanate (24mmol), in ultrasound reactor, stir.3min is reacted at 25 DEG C.Reaction terminates, and filters to obtain white crystal, i.e. embodiment 3.Fusing point > 300 C, yield is 62%.
1HNMR(400M,CDCl
3):1.50(t,
J=7.50Hz,3H,Me),3.10(q,
J=7.56Hz,2H,CH
2),6.81(t,
J=6.81Hz,1H,Py),7.29(d,
J=7.04Hz,1H,Py),7.85(d,
J=6.77Hz,1H,Py).3.87(s,3H,CH
3),6.85-7.26(m,4H,1Py-H,3Ph-H),7.82-8.26(m,3H,1Py-H,1Ph-H,1NH),8.90-9.16(m,2H,1NH,1Py-H),11.06(s,1H,NH).
The synthesis of embodiment 4N-(8-chloro-[1,2,4] triazolo [4,3-a] pyridine-3-carbonyl)-N-2-methyl-3-chloro-phenyl-urea
8-chloro-[1,2,4] triazole [4,3-a] pyridine hydrazides (20mmol) and 2-methyl-3-chlorophenyl isocyanate (24mmol), in ultrasound reactor, stir.3min is reacted at 25 DEG C.Reaction terminates, and filters to obtain light yellow crystal, i.e. embodiment 4.Fusing point > 300 C, yield is 78%.
1HNMR(CDCl
3,400MHz):2.27(s,3H,CH
3),7.17-7.26(m,3H,1Py-H,2Ph-H),7.83(d,
J=7.0Hz,1H,1Py-H),8.43(s,1H,NH),8.66(s,1H,NH),9.14(d,
J=6.8,1H,1Py-H),11.08(s,1H,NH).
The synthesis of embodiment 5N-(8-chloro-[1,2,4] triazolo [4,3-a] pyridine-3-amide group)-N-m-phenoxy phenylurea
8-chloro-[1,2,4] triazole [4,3-a] pyridine hydrazides (20mmol) and isophthalic methoxyphenyl isocyanate (24mmol), in ultrasound reactor, stir.3min is reacted at 25 DEG C.Reaction terminates, and filters to obtain white crystal, i.e. embodiment 5.Fusing point 268-272 C, yield is 85%.
1HNMR(CDCl
3,400MHz):6.96(t,
J=6.8Hz,4H,Ph-H),7.09(t,
J=6.8Hz,1H,Ph-H),7.25(t,
J=7.2Hz,1H,Py-H),7.36(t,
J=8.0Hz,2H,Ph-H),7.51(d,
J=8.8Hz,2H,Ph-H),7.84(d,
J=7.2Hz,1H,Py-H),8.45(s,1H,NH),8.87(s,1H,NH),9.14(d,
J=6.8Hz,1H,Py-H),11.01(s,1H,NH).
The synthesis of embodiment 6N-(8-chloro-[1,2,4] triazolo [4,3-a] pyridine-3-amide group)-N-3-aminomethyl phenyl urea
8-chloro-[1,2,4] triazole [4,3-a] pyridine hydrazides (20mmol) and 3-methylphenyl isocyanate (24mmol), in ultrasound reactor, stir.3min is reacted at 25 DEG C.Reaction terminates, and filters to obtain white crystal, i.e. embodiment 6.Fusing point > 300 C, yield is 80%.
1HNMR(CDCl
3,400MHz):2.25(s,3H,CH
3),6.78(d,
J=7.3Hz,1H,Ph-H),7.13(t,
J=8.5Hz,1H,Ph-H),7.22-7.31(m,3H,1Py-H,2Ph-H),7.83(d,
J=7.3Hz,1H,Py-H),8.40(s,1H,NH),8.75(s,1H,NH),9.13(d,
J=6.8Hz,1H,Py-H),10.99(s,1H,NH).
The synthesis of embodiment 7N-(8-chloro-[1,2,4] triazolo [4,3-a] pyridine-3-amide group)-N-2,5-dichlor-4-trifluoromethyl phenylurea
8-chloro-[1,2,4] triazole [4,3-a] pyridine hydrazides (20mmol) and 2,5-dichlor-4-trifluoromethyl phenyl isocyanate (24mmol), in ultrasound reactor, stir.3min is reacted at 25 DEG C.Reaction terminates, and filters to obtain white crystal, i.e. embodiment 7.Fusing point > 300 C, yield is 89%.
1HNMR(CDCl
3,400MHz):7.19(t,
J=7.0Hz,1H,Py-H),7.77(m,2H,1Py-H,1Ph-H),8.01(s,2H,1Ph-H,1NH),8.89(s,1H,NH),9.15(d,
J=7.0Hz,1H,Py-H),10.56(s,1H,NH).
The synthesis of embodiment 8N-(8-chloro-[1,2,4] triazolo [4,3-a] pyridine-3-amide group)-N-3,5-dichlorophenyl urea
8-chloro-[1,2,4] triazole [4,3-a] pyridine hydrazides (20mmol) and 3,5-dichlorophenyl isocyanate (24mmol), in ultrasound reactor, stir.3min is reacted at 25 DEG C.Reaction terminates, and filters to obtain yellow-green crystal, i.e. embodiment 8.Fusing point 260-265 C, yield is 77%.
1HNMR(CDCl
3,400MHz):7.25(t,
J=7.2Hz,1H,Py-H),7.6(m,1H,Ph-H),7.77-7.88(m,3H,1Py-H,2Ph-H),8.56(s,1H,NH),9.15(d,
J=4.0Hz,1H,Py-H),9.46(s,1H,NH),11.11(s,1H,NH).
The synthesis of embodiment 9N-(8-chloro-[1,2,4] triazolo [4,3-a] pyridine-3-amide group)-N-2,3-3,5-dimethylphenyl urea
8-chloro-[1,2,4] triazole [4,3-a] pyridine hydrazides (20mmol) and 2,3-dimethylphenyl isocyanate (24mmol), in ultrasound reactor, stir.3min is reacted at 25 DEG C.Reaction terminates, and filters to obtain light yellow crystal, i.e. embodiment 9.Fusing point > 300 C, yield is 88%.
1HNMR(CDCl
3,400MHz):2.12(s,3H,CH
3),2.25(s,3H,CH
3),6.92(m,1H,Ph-H),7.04(t,
J=7.6Hz,1H,Ph-H),7.25(t,
J=7.2Hz,1H,1Py-H),7.83(d,
J=7.3Hz,1H,Py-H),8.05(s,1H,Ph-H),8.15(s,1H,NH),8.51(s,1H,NH),9.15(d,
J=7.0Hz,1H,Py-H),11.01(s,1H,NH).
The synthesis of embodiment 10N-(8-chloro-[1,2,4] triazolo [4,3-a] pyridine-3-amide group)-N-2-methyl-4-nitrophenyl urea
8-chloro-[1,2,4] triazole [4,3-a] pyridine hydrazides (20mmol) and 2-methyl-4-nitrophenyl isocyanate (24mmol), in ultrasound reactor, stir.3min is reacted at 25 DEG C.Reaction terminates, and filters to obtain light yellow crystal, i.e. embodiment 10.Fusing point > 300 C, yield is 94%.
1HNMR(CDCl
3,400MHz):2.38(s,3H,CH
3),7.26(t,
J=7.1Hz,1H,Py-H),7.84(d,
J=7.3Hz,1H,Py-H),7.99(m,3H,Ph-H)8.50(s,1H,NH),9.05(s,1H,NH),9.14(d,
J=6.8Hz,1H,Py-H),11.19(s,1H,NH).
The synthesis of embodiment 11N-(8-chloro-[1,2,4] triazolo [4,3-a] pyridine-3-amide group)-N-2-methyl-3-trifluoromethyl urea
8-chloro-[1,2,4] triazole [4,3-a] pyridine hydrazides (20mmol) and 2-methyl-3-trifluoromethylbenzene based isocyanate (24mmol), in ultrasound reactor, stir.3min is reacted at 25 DEG C.Reaction terminates, and filters to obtain light yellow crystal, i.e. embodiment 11.Fusing point > 300 C, yield is 90%.
1HNMR(CDCl
3,400MHz):2.32(s,3H,CH
3),7.26(t,
J=7.1Hz,1H,Py-H),7.38(t,
J=7.5Hz,1H,Ph-H),7.48(t,
J=7.8Hz,2H,Ph-H),7.84(d,
J=7.3Hz,1H,Py-H),8.47(s,1H,NH),8.72(s,1H,NH),9.15(d,
J=6.8Hz,1H,Py-H),11.10(s,1H,NH)
The synthesis of embodiment 12N-(8-chloro-[1,2,4] triazolo [4,3-a] pyridine-3-amide group)-N-2-Trifluoromethoxyphen-l urea
8-chloro-[1,2,4] triazole [4,3-a] pyridine hydrazides (20mmol) and 2-Trifluoromethoxyphen-l isocyanic ester (24mmol), in ultrasound reactor, stir.3min is reacted at 25 DEG C.Reaction terminates, and filters to obtain white crystal, i.e. embodiment 12.Fusing point > 300 C, yield is 89%.
1HNMR(CDCl
3,400MHz):7.12(t,
J=7.1Hz,1H,Ph-H),7.25(t,
J=7.1Hz,1H,Py-H,),7.35(m,2H,Ph-H),7.83(d,
J=7.2Hz,1H,Py-H),8.16(d,
J=9.6Hz,1H,Ph-H),8.58(s,1H,NH),8.94(s,1H,NH),9.14(d,
J=6.9Hz,1H,Py-H),11.13(s,1H,NH).
The synthesis of embodiment 13N-(8-chloro-[1,2,4] triazolo [4,3-a] pyridine-3-amide group)-N-naphthyl urea
8-chloro-[1,2,4] triazole [4,3-a] pyridine hydrazides (20mmol) and naphthyl isocyanate (24mmol), in ultrasound reactor, stir.3min is reacted at 25 DEG C.Reaction terminates, and filters to obtain light yellow crystal, i.e. embodiment 13.Fusing point > 300 C, yield is 91%.
1HNMR(CDCl
3,400MHz):7.26(t,
J=7.2Hz,1H,Py-H),7.50(m,4H,Ph-H),7.70(t,
J=8.4Hz,1H,Ph-H),7.83(d,
J=7.3Hz,1H,Py-H),7.93(d,
J=8.2Hz,1H,Ph-H),8.13(d,
J=8.0Hz,1H,Ph-H),8.67(s,1H,NH),8.91(s,1H,NH),9.17(d,
J=7.2Hz,1H,Py-H),11.15(s,1H,NH).
The synthesis of embodiment 14N-(8-chloro-[1,2,4] triazolo [4,3-a] pyridine-3-amide group)-N-2-chloro-5-trifluoromethyl urea
8-chloro-[1,2,4] triazole [4,3-a] pyridine hydrazides (20mmol) and 2-chloro-5-trifluoromethylbenzene based isocyanate (24mmol), in ultrasound reactor, stir.3min is reacted at 25 DEG C.Reaction terminates, and filters to obtain light yellow crystal, i.e. embodiment 14.Fusing point 252-255 C, yield is 60%.
1HNMR(CDCl
3,400MHz):4.72(d,
J=6.4Hz,2H,Ph-H),7.20(t,
J=7.2Hz,1H,Py-H),7.46(m,1H,Ph-H),7.77(d,
J=7.2Hz,1H,Py-H),8.54(s,1H,NH),9.15(d,
J=7.2Hz,1H,Py-H),9.50(s,1H,NH),10.54(s,1H,NH).
Claims (5)
1. the preparation method of an amide urea type compound as shown in the formula (I), it is characterized in that described preparation method comprises the steps: the 8-chloro-[1 as shown in formula II, 2,4] triazole [4,3-a] pyridine hydrazides carries out Ultrasonic Radiation reaction in 0-60 DEG C with isocyanic ester as shown in formula III in acetonitrile, and fully after reaction, gained reaction solution processes and obtains product amide base carbamide compounds after filtration;
In formula (I) or formula (III), wherein R represents substituted-phenyl and naphthyl; The phenyl ring of described substituted-phenyl is monosubstituted or polysubstituted, described substituting group is selected from following groups: methyl, trifluoromethyl, nitro, phenoxy group, trifluoromethoxy, methoxyl group, halogen, hydrogen.
2. the preparation method of amide urea type compound as claimed in claim 1, it is characterized in that described isocyanic ester is selected from one of following: phenyl isocyanate, 2, 5-dimethylphenyl isocyanate, 2-methoxyphenyl isocyanate, 2-methyl-3-chlorophenyl isocyanate, 3-methylphenyl isocyanate, 2, 5-dichlor-4-trifluoromethyl phenyl isocyanate, 3, 5-dichlorophenyl isocyanate, 2, 3-dimethylphenyl isocyanate, 2-methyl-4-nitrophenyl isocyanate, 2-methyl-3-trifluoromethylbenzene based isocyanate, 2-Trifluoromethoxyphen-l isocyanic ester, naphthyl isocyanate, 2-chloro-5-trifluoromethylbenzene based isocyanate.
3. the preparation method of amide urea derivative as claimed in claim 1, is characterized in that described 8-chloro-[1,2,4] triazole [4,3-a] pyridine hydrazides: isocyanic ester: the molar ratio of acetonitrile is 1:1.0 ~ 1.5:2 ~ 20.
4. the preparation method of amide urea type compound as claimed in claim 1, it is characterized in that described temperature of reaction is 0-60 DEG C, the reaction times is 1-15min.
5. the preparation method of amide urea type compound as claimed in claim 1, it is characterized in that described temperature of reaction is 25 DEG C, the reaction times is 3min.
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| Design, Synthesis and Docking Studies of New 4-hydroxyquinoline-3-carbohydrazide Derivatives as Anti-HIV-1 Agents;Z. Hajimahdi, et al.;《Drug Research》;20130313;第63卷;第192-197页 * |
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