CN105294584A - 1-substituted phenyl-1H-1,2,3-triazole compound as well as preparation method and application thereof - Google Patents
1-substituted phenyl-1H-1,2,3-triazole compound as well as preparation method and application thereof Download PDFInfo
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- CN105294584A CN105294584A CN201510852576.5A CN201510852576A CN105294584A CN 105294584 A CN105294584 A CN 105294584A CN 201510852576 A CN201510852576 A CN 201510852576A CN 105294584 A CN105294584 A CN 105294584A
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
- C07D249/06—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles with aryl radicals directly attached to ring atoms
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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Abstract
The invention relates to a 1-substituted phenyl-1H-1,2,3-triazole compound, in particular to a compound applicable to preparation of anti-gout drugs and a preparation method of the compound, and belongs to the field of medicines. The compound is as shown in the general formula, wherein each R1 is independent alkyl of 1-10 carbons, 3-10 carbon atom naphthenic bases, allyl, methoxy ethyl, benzyl and substituted benzyl; substituted benzyl can be p-halogenated benzyl, p-cyano benzyl and p-alkoxy benzyl; each R2 is independent H or methyl; each R3 is independent H or ethyl. Experimental results show that the compound has a good effect in the in-vitro xanthine oxidase inhibition activity test.
Description
Technical field
The invention belongs to field of medicaments, relate to a kind of 1-substituted-phenyl-1
h-1,2,3-triazoles compounds, composition and method of making the same containing this compound.The invention still further relates to these compounds and the purposes of composition in antigout.
Background technology
Gout (Gout) is one group of heterogeneous, metabolism class disease because long-term hyperuricemia (Hyperuricemia) causes urate deposition to be formed in joint and soft tissue.Its clinical characters is: hyperuricemia, acute and chronic sacroiliitis, joint deformity, chronic interstitial nephritis and kidney knot etc., and severe patient also can concurrent renal failure and cardiovascular and cerebrovascular disease and threat to life.According to statistics, gout has become the second largest metabolic disease being only second to diabetes.In recent years along with the raising of living standards of the people and the change of dietary structure, the gout sickness rate of China, in the trend risen year by year, brings huge pressure and heavy economical load to society.
The pathogenesis of gout is: when uricogenesis in body increases or drain minimizing, and uric acid level in body can be caused to raise, and when exceeding its solubility limit, uric acid can be deposited on joint and soft tissue, and cause inflammation reaction.Uric acid is the final product of human body purine metabolism.XOD is a key enzyme in purine metabolism.In the final stage of purine metabolism, catalysis xanthine and xanthoglobulin oxidation generate uric acid, therefore suppress the activity of XOD effectively can reduce the generation of uric acid, in the treatment of hyperuricemia and gout, xanthine oxidase inhibitor occupies very important status.
The xanthine oxidase inhibitor gone on the market at present has allopurinol (Allopurinol), Febustat (Febuxostat) and holder department he (Topiroxostat), kind is very limited and have certain toxic side effect, therefore, the xanthine oxidase inhibitor developing high-efficiency low-toxicity has good market outlook.
Summary of the invention
Goal of the invention: the object of the present invention is to provide a kind of 1-substituted-phenyl-1H-1,2,3-triazole species new compound, prepared compound in vitro xanthine oxidase inhibitory activity has shown good effect in testing.Another object of the present invention is to provide described 1-substituted-phenyl-1H-1, the preparation method of 2,3-triazole species new compound.
Technical scheme:
The present invention is realized by following technical scheme:
A kind of 1-substituted-phenyl-1
h-1,2,3-triazoles compounds, is characterized in that: this compound is the such as compound shown in formula I, general formula II or its pharmaceutically acceptable salt, hydrate or solvate;
Wherein:
Each R1 is independently alkyl, a 3-10 carbon atom cycloalkyl, allyl group, methoxyethyl, benzyl, the substituted benzyl of 1-10 carbon; Substituted benzyl can be to halogeno-benzyl, to cyanobenzyls, to alkoxybenzyl;
Each R2 is independently H or methyl;
Each R3 is independently H or ethyl.
Described 1-substituted-phenyl-1
h-1,2,3-triazoles compounds, is characterized in that: the compound of described formula I be selected from following any one:
1-(3-cyano group-4-methoxyl group) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF01);
1-(3-cyano group-4-positive propoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF02);
1-(3-cyano group-4-isopropoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF03);
1-(3-cyano group-4-n-butoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF04);
1-(3-cyano-4-isobutoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF05);
1-(3-cyano group-4-sec-butoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF06);
1-(3-cyano group-4-n-pentyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF07);
1-(3-cyano group-4-isopentyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF08);
1-(the secondary pentyloxy of 3-cyano group-4-) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF09);
1-(3-cyano group-4-oxygen base in positive heptan) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF10);
1-(3-cyano group-4-n-octyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF11);
1-(3-cyano group-4-benzyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF12);
1-[3-cyano group-4-(4-chlorine) benzyloxy] phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF13);
1-[3-cyano group-4-(4-cyano group) benzyloxy] phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF14);
1-(3-cyano group-4-methoxyethoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF15);
1-(3-cyano group-4-allyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF16);
1-(3-cyano group-4-cyclopentyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF17);
1-[3-cyano group-4-(4-methoxyl group) benzyloxy] phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF18);
1-(3-cyano group-4-oxygen base just) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF19);
1-(3-cyano group-4-ring oxygen base) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF20);
5-methyl isophthalic acid-(3-cyano group-4-methoxyl group) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM01);
5-methyl isophthalic acid-(3-cyano group-4-positive propoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM02);
5-methyl isophthalic acid-(3-cyano group-4-isopropoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM03);
5-methyl isophthalic acid-(3-cyano group-4-n-butoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM04);
5-methyl isophthalic acid-(3-cyano-4-isobutoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM05);
5-methyl isophthalic acid-(3-cyano group-4-sec-butoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM06);
5-methyl isophthalic acid-(3-cyano group-4-n-pentyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM07);
5-methyl isophthalic acid-(3-cyano group-4-isopentyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM08);
5-methyl isophthalic acid-(the secondary pentyloxy of 3-cyano group-4-) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM09);
5-methyl isophthalic acid-(3-cyano group-4-oxygen base in positive heptan) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM10);
5-methyl isophthalic acid-(3-cyano group-4-n-octyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM11);
5-methyl isophthalic acid-(3-cyano group-4-benzyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM12);
5-methyl isophthalic acid-[3-cyano group-4-(4-chlorine) benzyloxy] phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM13);
5-methyl isophthalic acid-[3-cyano group-4-(4-cyano group) benzyloxy] phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM14);
5-methyl isophthalic acid-(3-cyano group-4-methoxyethoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM15);
5-methyl isophthalic acid-(3-cyano group-4-allyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM16);
5-methyl isophthalic acid-(3-cyano group-4-cyclopentyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM17);
5-methyl isophthalic acid-[3-cyano group-4-(4-methoxyl group) benzyloxy] phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM18);
5-methyl isophthalic acid-(3-cyano group-4-oxygen base just) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM19);
5-methyl isophthalic acid-(3-cyano group-4-ring oxygen base) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM20).
Described 1-substituted-phenyl-1
h-1,2,3-triazoles compounds, is characterized in that: the compound of described general formula II be selected from following any one:
2-methoxyl group-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP01);
2-positive propoxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP01);
2-isopropoxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP03);
2-n-butoxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP04);
2-isobutoxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP05);
2-sec-butoxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP06);
2-n-pentyloxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP7);
2-isopentyloxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP08);
Secondary pentyloxy-the 5-of 2-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP09);
2-oxygen base in positive heptan-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP10);
2-n-octyloxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP11);
2-benzyloxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP12);
2-(4-chlorine) benzyloxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP13);
2-(4-cyano group) benzyloxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP14);
2-methoxyethoxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP15);
2-allyloxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP16);
2-cyclopentyloxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP17);
2-(4-methoxyl group) benzyloxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP8);
2-is oxygen base-5-(4-(pyridin-4-yl)-1 just
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP19);
2-ring is oxygen base-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP20).
A kind of medicinal compositions, is characterized in that: comprise above-mentioned compound, its pharmacy acceptable salt, hydrate or solvate described in any one and pharmaceutically acceptable carrier.
A preparation method for compound as described above, is characterized in that:
The preparation of compound shown in formula I, concrete steps are:
(1) take salicylonitrile as starting raw material, through nitrated, alkylation, reduction, diazotization obtains important intermediate 5-azido--2-alkoxy benzene formonitrile HCN;
(2) 5-azido--2-alkoxy benzene formonitrile HCN and ethyl propiolate are through Husigen cycloaddition reaction, then are hydrolyzed, and obtain R
2for the compound of H atom;
(3) 5-amino-2-alkoxy benzene formonitrile HCN and diethyl malonate are through ring-closure reaction, then are hydrolyzed, and obtain R
2for the compound of methyl;
The preparation of compound shown in general formula II, concrete steps are:
(1) take salicylonitrile as starting raw material, through nitrated, alkylation, reduction, diazotization obtains important intermediate 5-azido--2-alkoxy benzene formonitrile HCN;
(2) 5-azido--2-alkoxy benzene formonitrile HCN and 4-ethynyl pyridine hydrochloride are through Husigen cycloaddition reaction, obtain the compound shown in general formula II.
Compound above described in any one, its pharmacy acceptable salt, hydrate or solvate or described composition are preparing the application in anti-gout drugs.
Described 1-substituted-phenyl-1
h-1,2,3-triazoles compounds is preparing the application in anti-gout drugs, it is characterized in that: described 1-substituted-phenyl-1
h-1,2,3-triazoles compounds is the compound above described in any one, its pharmacy acceptable salt, hydrate or solvate or described medicinal compositions.
Advantage and effect: preparation method's simple possible of the triazole species new compound of formula I provided by the present invention and general formula II, yield is better.
embodiment:
The present invention relates to a kind of 1-substituted-phenyl-1
h-1,2,3-triazoles compounds, is characterized in that: this compound is the such as compound shown in formula I, general formula II or its pharmaceutically acceptable salt, hydrate or solvate;
Wherein:
Each R1 is independently alkyl, a 3-10 carbon atom cycloalkyl, allyl group, methoxyethyl, benzyl, the substituted benzyl of 1-10 carbon; Substituted benzyl can be to halogeno-benzyl, to cyanobenzyls, to alkoxybenzyl;
Each R2 is independently H or methyl;
Each R3 is independently H or ethyl.
Compound shown in formula I and general formula II, pharmaceutically acceptable salt comprises sodium salt, sylvite, calcium salt, ethylenediamine salt etc.; Pharmaceutically acceptable hydrate comprises monohydrate, dihydrate, pentahydrate etc.; Pharmaceutically acceptable solvate comprises ethanolates, di-methylcarbinol compound etc.
Compound shown in formula I and general formula II can also make composite preparation with pharmaceutically acceptable auxiliary materials such as starch, Microcrystalline Cellulose, hard magnesium, glycerine.
The preparation method of this compound is further illustrated below by embodiment:
Embodiment 1
The preparation of 5-nitro-2-hydroxy-phenylformonitrile
In 500mL reaction flask, add salicylonitrile (100g, 0.84mol) and glacial acetic acid (200mL), under 50 DEG C of stirrings, slowly drip concentrated nitric acid (74.4mL, 1.1mol), control temperature of reaction between 50-70 DEG C, finish and continue reaction 4h, cool after completion of the reaction, pour in frozen water, suction filtration, filter cake massive laundering, seasoning, obtain faint yellow solid 82g, yield: 59.5%.
Embodiment 2
The preparation of 5-amino-2-alkoxy benzene formonitrile HCN
5-nitro-2-hydroxy-phenylformonitrile (110mmol) is added, halogenated alkane (110mmol), Anhydrous potassium carbonate (165mmol) potassiumiodide (11mmol) and DMF(80mL) in reaction flask, at 60 DEG C, reaction is spent the night, and TCL reacts completely, after reaction solution cooling, pour in 300mL water, ethyl acetate (100mL*3) extracts, and organic layer is washed, and saturated common salt is washed, anhydrous sodium sulfate drying spends the night, filter, filtrate reduced in volume, to dry, obtains pale yellow oil.
The preparation (58.2mol) of 5-nitro-2-alkoxy benzene formonitrile HCN prepared by upper step is added in reaction flask, and reduced iron powder (223.8mmol), ammonium chloride (29.1mmol), ethanol (15mL) and water (45mL), backflow 3h, reacts completely, thin up, ethyl acetate (50mL*3) extracts, saturated common salt is washed, anhydrous sodium sulfate drying, filters, be evaporated to dry smart product, column chromatography purification (ethyl acetate: sherwood oil=1:5 ~ 1:1) sterling.
(1) 5-amino-2-methoxy benzonitrile
Off-white powder, yield: 52.0%.
(2) 5-amino-2-positive propoxy cyanobenzene
Yellow oil, yield: 45.2%.
(3) 5-amino-2-isopropoxy cyanobenzene
Yellow oil, yield: 52.6%.
(4) 5-amino-2-n-butoxy cyanobenzene
Yellow solid, yield: 42.0%.
(5) 5-amino-2-isobutoxy cyanobenzene
Yellow solid, yield: 53.4%.
(6) 5-amino-2-sec-butoxy cyanobenzene
Yellow oil, yield: 42.3%.
(7) 5-amino-2-n-pentyloxy cyanobenzene
Yellow oil, yield: 36.4%.
(8) 5-amino-2-isopentyloxy cyanobenzene
Yellow oil, yield: 39.1%.
(9) the secondary amyl phenyl ether formonitrile HCN of 5-amino-2-
Yellow oil, yield: 51.2%.
(10) the positive heptyloxybenzene formonitrile HCN of 5-amino-2-
Yellow oil, yield: 42.4%.
(11) 5-amino-2-n-octyloxy cyanobenzene
Yellow oil, yield: 34.8%.
(12) 5-amino-2-benzyloxy cyanobenzene
Yellow powder, yield: 42.7%.
(13) 5-amino-2-(4-chlorine) benzyloxy cyanobenzene
Off-white color plate crystal, yield: 29.9%.
(14) 5-amino-2-(4-cyanogen) benzyloxy cyanobenzene
Off-white powder, yield: 50.0%.
(15) 5-amino-2-methoxyethoxy cyanobenzene
Off-white color solid, yield: 52.1%.
(16) 5-amino-2-allyloxy cyanobenzene
Pale tan oil, yield: 34.2%.
(17) 5-amino-2-cyclopentyloxy cyanobenzene
Yellow powder, yield: 36.1%.
(18) 5-amino-2-(4-methoxy) benzyloxy cyanobenzene
Yellow scaled crystal, yield: 42.8%.
(19) 5-amino-2-ring oxygen base cyanobenzene
Yellow powder, yield: 18.8%.
Embodiment 3
The preparation of 5-azido--2-alkoxy benzene formonitrile HCN
5-amino-2-alkoxy benzene formonitrile HCN (20mmol) is added in reaction flask, glacial acetic acid (50mL) and water (20mL), under-10 DEG C of stirrings, the water-soluble Sodium Nitrite of slow dropping 20mL (26mmol), add and drip reaction 30min, the water-soluble sodiumazide of slow dropping 20mL (30mmol), finish, surely hold thermotonus 3h, dichloromethane extraction, merge organic layer, saturated common salt is washed, anhydrous sodium sulfate drying, filters, be evaporated to dry thick product, column chromatography purification (ethyl acetate: sherwood oil=1:5) sterling.
(1) 5-azido--2-methoxy benzonitrile
Yellow needles, yield: 78.2%.
1HNMR(600MHz,DMSO)δ7.56(d,
J=2.8Hz,1H),7.44(dd,
J=9.1,2.9Hz,1H),7.28(d,
J=9.1Hz,1H),3.91(s,3H).
(2) 5-azido--2-positive propoxy cyanobenzene
Yellow oil, yield: 72.0%.
1HNMR(600MHz,DMSO)δ7.54(s,1H),7.40(dd,
J=9.0,2.7Hz,1H),7.27(d,
J=9.1Hz,1H),4.08(t,
J=6.4Hz,2H),1.81–1.68(m,2H),0.99(t,
J=7.4Hz,3H).
(3) 5-azido--2-isopropoxy cyanobenzene
Yellow oil, yield: 72.3%.
1HNMR(600MHz,DMSO)δ7.52(d,
J=2.8Hz,1H),7.38(dd,
J=9.1,2.9Hz,1H),7.30(d,
J=9.1Hz,1H),4.75(dt,
J=12.1,6.0Hz,1H),1.30(d,
J=6.0Hz,6H).
(4) 5-azido--2-n-butoxy cyanobenzene
Yellow oil, yield: 65.8%.
1HNMR(600MHz,DMSO)δ7.53(d,
J=2.8Hz,1H),7.39(dd,
J=9.0,2.9Hz,1H),7.27(d,
J=9.1Hz,1H),4.12(t,
J=6.4Hz,2H),1.72(dt,
J=18.7,6.4Hz,2H),1.50–1.40(m,2H),0.94(t,
J=7.4Hz,3H).
(5) 5-azido--2-isobutoxy cyanobenzene
Yellow solid, yield: 72.3%.
1HNMR(600MHz,DMSO)δ7.54(d,
J=2.8Hz,1H),7.40(dd,
J=9.0,2.9Hz,1H),7.27(d,
J=9.1Hz,1H),3.90(d,
J=6.5Hz,2H),2.04(dt,
J=13.3,6.6Hz,1H),0.99(d,
J=6.7Hz,6H).
(6) 5-azido--2-sec-butoxy cyanobenzene
Yellow oil, yield: 74.3%.
1HNMR(600MHz,DMSO)δ7.53(d,
J=2.8Hz,1H),7.38(dd,
J=9.1,2.9Hz,1H),7.30(d,
J=9.1Hz,1H),4.56(h,
J=6.0Hz,1H),1.73–1.56(m,2H),1.26(d,
J=6.1Hz,3H),0.93(d,
J=7.4Hz,3H).
(7) 5-azido--2-n-pentyloxy cyanobenzene
Yellow oil, yield: 52.9%.
1HNMR(600MHz,DMSO)δ7.53(d,
J=2.8Hz,1H),7.39(dd,
J=9.0,2.9Hz,1H),7.27(d,
J=9.1Hz,1H),4.11(t,
J=6.5Hz,2H),1.79–1.64(m,2H),1.44–1.37(m,2H),1.37–1.30(m,2H),0.89(t,
J=7.2Hz,3H).
(8) 5-azido--2-isopentyloxy cyanobenzene
Yellow solid, yield: 47.9%.
1HNMR(600MHz,DMSO)δ7.53(d,
J=2.8Hz,1H),7.40(dd,
J=9.0,2.8Hz,1H),7.29(d,
J=9.1Hz,1H),4.14(t,
J=6.6Hz,2H),1.80(dp,
J=13.4,6.7Hz,1H),1.64(q,
J=6.6Hz,2H),0.93(d,
J=6.7Hz,6H).
(9) the secondary amyl phenyl ether formonitrile HCN of 5-azido--2-
Yellow oil, yield: 53.6%.
1HNMR(600MHz,DMSO)δ7.52(d,
J=2.8Hz,1H),7.38(dd,
J=9.1,2.9Hz,1H),7.30(d,
J=9.1Hz,1H),4.61(h,
J=6.0Hz,1H),1.70–1.61(m,1H),1.56(ddd,
J=15.2,12.5,5.7Hz,1H),1.46–1.33(m,2H),1.26(d,
J=6.1Hz,3H),0.89(t,
J=7.4Hz,3H).
(10) the positive heptyloxybenzene formonitrile HCN of 5-azido--2-
Yellow oil, yield: 49.8%.
1HNMR(600MHz,DMSO)δ7.54(d,
J=2.8Hz,1H),7.40(dd,
J=9.0,2.9Hz,1H),7.27(d,
J=9.1Hz,1H),4.11(t,
J=6.4Hz,2H),1.77–1.66(m,2H),1.46–1.37(m,2H),1.37–1.21(m,6H),0.86(t,
J=6.9Hz,3H).
(11) 5-azido--2-n-octyloxy cyanobenzene
Yellow oil, yield: 78.2%.
1HNMR(600MHz,DMSO)δ7.53(d,
J=1.8Hz,1H),7.39(d,
J=9.0Hz,1H),7.26(d,
J=9.0Hz,1H),4.10(t,
J=6.3Hz,2H),1.83–1.64(m,2H),1.50–1.36(m,2H),1.36–1.18(m,8H),0.85(t,
J=6.5Hz,3H).
(12) 5-azido--2-benzyloxy cyanobenzene
Yellow powder, yield: 91.8%.
1HNMR(600MHz,DMSO)δ7.58(d,
J=2.8Hz,1H),7.47(d,
J=7.3Hz,2H),7.44–7.40(m,3H),7.39–7.33(m,2H),5.29(s,2H).
(13) 5-azido--2-(4-chlorine) benzyloxy cyanobenzene
Yellow powder, yield: 76.8%.
1HNMR(600MHz,DMSO)δ7.58(d,
J=2.8Hz,1H),7.49(s,4H),7.43(dd,
J=9.1,2.8Hz,1H),7.35(d,
J=9.1Hz,1H),5.28(s,2H).
(14) 5-azido--2-(4-cyanogen) benzyloxy cyanobenzene
Pale yellow powder, yield: 85.2%.
1HNMR(600MHz,DMSO)δ7.90(d,
J=8.0Hz,2H),7.65(d,
J=8.1Hz,2H),7.60(d,
J=2.3Hz,1H),7.43(dd,
J=9.0,2.4Hz,1H),7.33(d,
J=9.1Hz,1H),5.40(s,2H).
(15) 5-azido--2-methoxyethoxy cyanobenzene
Yellow plate crystal, yield: 79.2%.
1HNMR(600MHz,DMSO)δ7.55(d,
J=1.7Hz,1H),7.41(dd,
J=9.0,2.8Hz,1H),7.30(d,
J=9.1Hz,1H),4.26(dd,
J=4.8,4.0Hz,2H),3.74–3.65(m,2H).
(16) 5-azido--2-allyloxy cyanobenzene
Yellow oil, yield: 76.2%.
(17) 5-azido--2-cyclopentyloxy cyanobenzene
Yellow powder, yield: 74.6%.
1HNMR(600MHz,DMSO)δ7.53(d,
J=2.8Hz,1H),7.39(dd,
J=9.1,2.9Hz,1H),7.28(d,
J=9.1Hz,1H),4.98(t,
J=5.6Hz,1H),1.98–1.86(m,2H),1.72(q,
J=7.9Hz,4H),1.67–1.53(m,2H).
(18) 5-azido--2-(4-methoxy) benzyloxy cyanobenzene
Yellow powder, yield: 74.3%.
1HNMR(600MHz,DMSO)δ7.55(d,
J=2.7Hz,1H),7.43–7.35(m,4H),6.97(d,
J=8.7Hz,2H),5.19(s,2H),3.76(s,3H).
Embodiment 4
1-(3-cyano group-4-alkoxyl group) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
Salzburg vitriol (89 μm of ol) is added in reaction flask, vitamins C (89 μm of ol), ethanol (10mL) and water (10mL), stirred at ambient temperature 15min, then add 5-azido--2-alkoxy benzene formonitrile HCN (742 μm of ol) and ethyl propiolate (3710 μm of ol), microwave reaction 8min at 50 DEG C, react completely, thin up, suction filtration, the ethanolic soln recrystallization of filter cake 10%-30%.
(1) 1-(3-cyano group-4-methoxyl group) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
Pale yellow powder, yield: 75.3%.
(2) 1-(3-cyano group-4-positive propoxy) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
Off-white color plate crystal, yield: 72.3%.
1HNMR(600MHz,DMSO)δ8.12(d,
J=2.6Hz,1H),7.92(dd,
J=9.0,2.7Hz,1H),7.49(d,
J=9.1Hz,1H),4.36(t,
J=7.1Hz,2H),4.22(t,
J=6.4Hz,2H),2.49(s,3H),1.92–1.74(m,2H),1.33(t,
J=7.1Hz,3H),1.03(t,
J=7.4Hz,3H).
(3) 1-(3-cyano group-4-isopropoxy) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
The crystallization of off-white color head, yield: 94.2%.
(4) 1-(3-cyano group-4-n-butoxy) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
Faint yellow scaled crystal, yield: 72.0%.
(5) 1-(3-cyano-4-isobutoxy) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
White scaled crystal, yield: 84.0%.
(6) 1-(3-cyano group-4-sec-butoxy) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
Off-white powder, yield: 62.5%.
(7) 1-(3-cyano group-4-n-pentyloxy) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
White scaled crystal, yield: 73.4%.
(8) 1-(3-cyano group-4-isopentyloxy) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
Off-white powder, yield: 59.8%.
(9) 1-(the secondary pentyloxy of 3-cyano group-4-) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
Off-white powder, yield: 83.4%.
(10) 1-(3-cyano group-4-oxygen base in positive heptan) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
Off-white powder, yield: 94.2%.
(11) 1-(3-cyano group-4-n-octyloxy) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
Yellow powder, yield: 45.2%.
(12) 1-(3-cyano group-4-benzyloxy) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
Yellow powder, yield: 62.4%.
(13) 1-(3-cyano group-4-(4-chlorine) benzyloxy) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
Off-white powder, yield: 76.1%.
(14) 1-(3-cyano group-4-(4-cyano group) benzyloxy) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
Off-white powder, yield: 49.8%.
(15) 1-(3-cyano group-4-methoxyethoxy) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
Off-white color needle crystal, yield: 78.2%.
1HNMR(600MHz,DMSO)δ8.13(d,
J=2.6Hz,1H),7.93(dd,
J=9.0,2.7Hz,1H),7.52(d,
J=9.1Hz,1H),4.42–4.38(m,2H),4.36(q,
J=7.1Hz,2H),3.79–3.69(m,2H),3.36(s,3H),2.49(s,3H),1.33(t,
J=7.1Hz,3H).
(16) 1-(3-cyano group-4-allyloxy) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
Off-white powder, yield: 84.2%.
1HNMR(600MHz,DMSO)δ8.14(d,
J=2.6Hz,1H),7.93(dd,
J=9.0,2.7Hz,1H),7.49(d,
J=9.1Hz,1H),6.10(ddd,
J=22.4,10.4,5.1Hz,1H),5.50(dd,
J=18.0,2.4Hz,1H),5.36(dd,
J=10.6,1.4Hz,1H),4.87(d,
J=5.2Hz,2H),4.36(q,
J=7.1Hz,2H),2.49(s,3H),1.33(t,
J=7.1Hz,3H).
(17) 1-(3-cyano group-4-cyclopentyloxy) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
Off-white powder, yield: 77.8%.
1HNMR(600MHz,DMSO)δ8.10(d,
J=2.6Hz,1H),7.90(dd,
J=9.0,2.7Hz,1H),7.49(d,
J=9.1Hz,1H),5.17–5.10(m,1H),4.35(q,
J=7.1Hz,2H),2.49(s,3H),2.05–1.95(m,2H),1.77(ddd,
J=19.9,13.8,5.7Hz,4H),1.69–1.59(m,2H),1.33(t,
J=7.1Hz,3H).
(18) 1-(3-cyano group-4-(4-methoxyl group) benzyloxy) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
White powder, yield: 68.5%.
1HNMR(600MHz,DMSO)δ8.07(d,
J=2.6Hz,1H),7.88(dd,
J=9.0,2.6Hz,1H),7.56(d,
J=9.2Hz,1H),7.45(d,
J=8.6Hz,2H),7.00(d,
J=8.6Hz,2H),5.30(s,2H),3.77(s,3H),2.49(s,3H).
Embodiment 5
1-(3-cyano group-4-alkoxyl group) phenyl-1
h-1,2,3-triazoles-4-formic acid
1-(3-cyano group-4-alkoxyl group) phenyl-1 is added in reaction flask
h-1,2,3-triazoles-4-ethyl formate (383 μm of ol), NaOH(2300 μm of ol), ethanol (10mL) and water (25mL), react 1h at 50 DEG C and react completely, and 5% dilute hydrochloric acid adjusts pH to 3, separates out solid, suction filtration, dry, the ethanolic soln recrystallization of crude product 10%-30%.
(1) 1-(3-cyano group-4-methoxyl group) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF01)
Purple powder, yield: 59.2%.
1HNMR(600MHz,DMSO)δ9.33(s,1H),8.38(d,
J=2.5Hz,1H),8.27(dd,
J=9.1,2.5Hz,1H),7.48(d,
J=9.2Hz,1H),4.00(s,3H).
(2) 1-(3-cyano group-4-positive propoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF02)
White powder, yield: 64.2%.
1HNMR(600MHz,DMSO)δ8.11(d,
J=2.7Hz,1H),7.92(dd,
J=9.0,2.7Hz,1H),7.49(d,
J=9.1Hz,1H),4.22(t,
J=6.4Hz,2H),2.48(s,3H),1.94–1.67(m,2H),1.03(t,
J=7.4Hz,3H).
(3) 1-(3-cyano group-4-isopropoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF03)
White powder, yield: 48.2%.
1HNMR(600MHz,DMSO)δ9.22(s,1H),8.35(s,1H),8.22(dd,
J=9.1,2.2Hz,1H),7.50(d,
J=9.3Hz,1H),4.90(hept,
J=6.0Hz,1H),1.35(d,
J=6.0Hz,6H).
(4) 1-(3-cyano group-4-n-butoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF04)
Pale yellow powder, yield: 90.2%.
1HNMR(600MHz,DMSO)δ9.32(s,1H),8.37(d,
J=2.1Hz,1H),8.24(dd,
J=9.1,2.1Hz,1H),7.48(d,
J=9.2Hz,1H),4.19(t,
J=6.4Hz,2H),1.80(dd,
J=13.9,6.6Hz,2H),1.02(t,
J=7.4Hz,3H).
(5) 1-(3-cyano-4-isobutoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF05)
Off-white powder, yield: 79.2%.
1HNMR(600MHz,DMSO)δ9.25(s,1H),8.37(d,
J=2.4Hz,1H),8.23(dd,
J=9.1,2.3Hz,1H),7.47(d,
J=9.2Hz,1H),4.01(d,
J=6.5Hz,2H),2.09(dt,
J=13.3,6.6Hz,1H),1.02(d,
J=6.7Hz,6H).
(6) 1-(3-cyano group-4-sec-butoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF06)
Yellow powder, yield: 43.2%.
1HNMR(600MHz,DMSO)δ8.96(s,1H),8.33(s,1H),8.22(s,1H),7.46(d,
J=8.7Hz,1H),4.23(d,
J=6.5Hz,1H),1.68(dd,
J=13.4,6.6Hz,2H),0.97(d,
J=5.4Hz,3H),0.95(s,3H).
(7) 1-(3-cyano group-4-n-pentyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF07)
Off-white powder, yield: 36.1%.
1HNMR(600MHz,DMSO)δ9.22(s,1H),8.35(s,1H),8.22(d,
J=5.3Hz,1H),7.46(d,
J=8.6Hz,1H),4.22(t,
J=6.4Hz,2H),1.87–1.70(m,2H),1.42(dd,
J=18.6,11.4Hz,2H),1.37(dd,
J=14.7,7.3Hz,2H),0.90(t,
J=7.2Hz,3H).
(8) 1-(3-cyano group-4-isopentyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF08)
Off-white powder, yield: 29.8%.
1HNMR(600MHz,DMSO)δ9.04(s,1H),8.29(d,
J=2.1Hz,1H),8.19(dd,
J=9.1,2.1Hz,1H),7.44(d,
J=9.2Hz,1H),4.22(t,
J=6.6Hz,2H),1.82(dt,
J=13.4,6.7Hz,1H),1.68(q,
J=6.6Hz,2H),0.95(d,
J=6.6Hz,6H).
(9) 1-(3-cyano group-4-oxygen base in positive heptan) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF10)
Off-white powder, yield: 51.0%.
1HNMR(600MHz,DMSO)δ9.32(s,1H),8.38(s,1H),8.24(d,
J=7.5Hz,1H),7.47(d,
J=9.1Hz,1H),4.22(t,
J=6.4Hz,2H),1.87–1.68(m,2H),1.49–1.38(m,2H),1.38–1.17(m,6H),0.87(t,
J=6.9Hz,3H).
(10) 1-(3-cyano group-4-n-octyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF11)
Off-white powder, yield: 43.6%.
1HNMR(600MHz,DMSO)δ9.21(s,1H),8.35(d,
J=2.6Hz,1H),8.22(dd,
J=9.1,2.6Hz,1H),7.46(d,
J=9.3Hz,1H),4.21(t,
J=6.4Hz,2H),1.87–1.67(m,2H),1.44(dd,
J=15.2,7.6Hz,2H),1.38–1.18(m,8H),0.86(t,
J=6.9Hz,3H).
(11) 1-(3-cyano group-4-benzyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF12)
Off-white powder, yield: 95.0%.
1HNMR(600MHz,DMSO)δ9.09(s,1H),8.39(s,1H),8.27(d,
J=6.4Hz,1H),7.54(d,
J=6.7Hz,3H),7.43(t,
J=7.5Hz,2H),7.37(t,
J=7.3Hz,1H),5.36(s,2H).
(12) 1-(3-cyano group-4-(4-chlorine) benzyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF13)
Off-white powder, yield: 75.6%.
1HNMR(600MHz,DMSO)δ8.97(s,1H),8.36(s,1H),8.24(d,
J=8.2Hz,1H),7.54–7.45(m,5H),5.36(s,2H).
(13) 1-(3-cyano group-4-(4-cyano group) benzyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF14)
Off-white powder, yield: 87.3%.
1HNMR(600MHz,DMSO)δ9.18(s,1H),8.41(d,
J=1.3Hz,1H),8.27(d,
J=8.3Hz,1H),7.93(d,
J=8.2Hz,2H),7.69(d,
J=8.1Hz,2H),7.53(d,
J=9.2Hz,1H),5.50(s,2H).
(14) 1-(3-cyano group-4-methoxyethoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF15)
White powder, yield: 76.4%.
1HNMR(600MHz,DMSO)δ9.07(s,1H),8.33(d,
J=2.7Hz,1H),8.22(dd,
J=9.2,2.7Hz,1H),7.47(d,
J=9.3Hz,1H),4.42–4.30(m,2H),3.79–3.67(m,2H).
Embodiment 6
5-methyl isophthalic acid-(3-cyano group-4-alkoxyl group) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
5-methyl isophthalic acid-(3-cyano group-4-alkoxyl group) phenyl-1 is added in reaction flask
h-1,2,3-triazoles-4-ethyl formate (200 μm of ol), diethyl malonate (600 μm of ol), sodium ethylate (420 μm of ol) and ethanol (15mL), back flow reaction 2h, TCL react completely, evaporated under reduced pressure is about the solvent of half, thin up, suction filtration, dry, the ethanolic soln recrystallization of crude product 10%-30%, obtains sterling.
(1) 5-methyl isophthalic acid-(3-cyano group-4-methoxyl group) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
Off-white powder, yield: 94.2%.
(2) 5-methyl isophthalic acid-(3-cyano group-4-positive propoxy) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
Off-white color plate crystal, yield: 97.5%.
1HNMR(600MHz,DMSO)δ8.12(d,
J=2.6Hz,1H),7.92(dd,
J=9.0,2.7Hz,1H),7.49(d,
J=9.1Hz,1H),4.36(t,
J=7.1Hz,2H),4.22(t,
J=6.4Hz,2H),2.49(s,3H),1.92–1.74(m,2H),1.33(t,
J=7.1Hz,3H),1.03(t,
J=7.4Hz,3H).
(3) 5-methyl isophthalic acid-(3-cyano group-4-isopropoxy) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
Off-white powder, yield: 93.5%.
(4) 5-methyl isophthalic acid-(3-cyano group-4-n-butoxy) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
White scaled crystal, yield: 94.2%.
(5) 5-methyl isophthalic acid-(3-cyano-4-isobutoxy) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
White scaled crystal, yield: 90.1%.
(6) 5-methyl isophthalic acid-(3-cyano group-4-sec-butoxy) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
Off-white powder, yield: 85.9%.
(7) 5-methyl isophthalic acid-(3-cyano group-4-n-pentyloxy) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
White scaled crystal, yield: 75.3%.
(8) 5-methyl isophthalic acid-(3-cyano group-4-isopentyloxy) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
White scaled crystal, yield: 94.2%.
(9) 5-methyl isophthalic acid-(the secondary pentyloxy of 3-cyano group-4-) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
Off-white powder, yield: 95.1%.
(10) 5-methyl isophthalic acid-(3-cyano group-4-oxygen base in positive heptan) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
Off-white powder, yield: 67.5%.
(11) 5-methyl isophthalic acid-(3-cyano group-4-n-octyloxy) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
Off-white color plate crystal, yield: 78.6%.
(12) 5-methyl isophthalic acid-(3-cyano group-4-benzyloxy) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
Off-white powder, yield: 86.7%.
(13) 5-methyl isophthalic acid-(3-cyano group-4-(4-chlorine) benzyloxy) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
Off-white powder, yield: 59.8%.
(14) 5-methyl isophthalic acid-(3-cyano group-4-(4-cyano group) benzyloxy) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
Off-white powder, yield: 74.4%.
(15) 5-methyl isophthalic acid-(3-cyano group-4-methoxyethoxy) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
White scaled crystal, yield: %.
1HNMR(600MHz,DMSO)δ8.13(d,
J=2.6Hz,1H),7.93(dd,
J=9.0,2.7Hz,1H),7.52(d,
J=9.1Hz,1H),4.42–4.38(m,2H),4.36(q,
J=7.1Hz,2H),3.79–3.69(m,2H),3.36(s,3H),2.49(s,3H),1.33(t,
J=7.1Hz,3H).
(16) 5-methyl isophthalic acid-(3-cyano group-4-allyloxy) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
Off-white powder, yield: 88.5%.
1HNMR(600MHz,DMSO)δ8.14(d,
J=2.6Hz,1H),7.93(dd,
J=9.0,2.7Hz,1H),7.49(d,
J=9.1Hz,1H),6.10(ddd,
J=22.4,10.4,5.1Hz,1H),5.50(dd,
J=18.0,2.4Hz,1H),5.36(dd,
J=10.6,1.4Hz,1H),4.87(d,
J=5.2Hz,2H),4.36(q,
J=7.1Hz,2H),2.49(s,3H),1.33(t,
J=7.1Hz,3H).
(17) 5-methyl isophthalic acid-(3-cyano group-4-cyclopentyloxy) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
Off-white powder, yield: 94.2%.
1HNMR(600MHz,DMSO)δ8.10(d,
J=2.6Hz,1H),7.90(dd,
J=9.0,2.7Hz,1H),7.49(d,
J=9.1Hz,1H),5.17–5.10(m,1H),4.35(q,
J=7.1Hz,2H),2.49(s,3H),2.05–1.95(m,2H),1.77(ddd,
J=19.9,13.8,5.7Hz,4H),1.69–1.59(m,2H),1.33(t,
J=7.1Hz,3H).
(18) 5-methyl isophthalic acid-(3-cyano group-4-(4-methoxyl group) benzyloxy) phenyl-1
h-1,2,3-triazoles-4-ethyl formate
White powder, yield: 79.2%.
Embodiment 8
5-methyl isophthalic acid-(3-cyano group-4-alkoxyl group) phenyl-1
h-1,2,3-triazoles-4-formic acid
5-methyl isophthalic acid-(3-cyano group-4-alkoxyl group) phenyl-1 is added in reaction flask
h-1,2,3-triazoles-4-ethyl formate (373 μm of ol), NaOH(1860 μm of ol), methyl alcohol (20mL) and water (10mL), react 1.5h at 50 DEG C and react completely, remove the solvent of about half under reduced pressure, thin up, 5% dilute hydrochloric acid adjusts pH to 3, separates out solid, suction filtration, drying, the ethanolic soln recrystallization of crude product 10%-30%.
(1) 5-methyl isophthalic acid-(3-cyano group-4-methoxyl group) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM01)
Off-white powder, yield: 51.2%.
1HNMR(600MHz,DMSO)δ8.07(d,
J=2.6Hz,1H),7.90(dd,
J=9.0,2.6Hz,1H),7.46(d,
J=9.1Hz,1H),4.01(s,3H),2.49(d,
J=1.7Hz,3H).
(2) 5-methyl isophthalic acid-(3-cyano group-4-positive propoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM02)
Off-white powder, yield: 49.8%.
(3) 5-methyl isophthalic acid-(3-cyano group-4-isopropoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM03)
White powder, yield: 70.0%.
1HNMR(600MHz,DMSO)δ8.04(d,
J=2.6Hz,1H),7.84(dd,
J=9.1,2.6Hz,1H),7.48(d,
J=9.3Hz,1H),4.91(dt,
J=12.1,6.0Hz,1H),2.51(s,3H),1.37(d,
J=6.0Hz,6H).
(4) 5-methyl isophthalic acid-(3-cyano group-4-n-butoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM04)
White powder, yield: 49.7%.
1HNMR(600MHz,DMSO)δ8.10(d,
J=2.6Hz,1H),7.90(dd,
J=9.0,2.6Hz,1H),7.48(d,
J=9.1Hz,1H),4.25(t,
J=6.4Hz,2H),2.49(s,3H),1.82–1.73(m,2H),1.54–1.43(m,2H),0.97(t,
J=7.4Hz,3H).
(5) 5-methyl isophthalic acid-(3-cyano-4-isobutoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM05)
White powder, yield: 75.3%.
1HNMR(600MHz,DMSO)δ8.06(d,
J=2.2Hz,1H),7.86(dd,
J=8.9,2.0Hz,1H),7.45(d,
J=9.1Hz,1H),4.02(d,
J=6.4Hz,2H),2.50(s,3H),2.10(dd,
J=13.3,6.6Hz,1H),1.03(d,
J=6.7Hz,6H).
(6) 5-methyl isophthalic acid-(3-cyano group-4-sec-butoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM06)
White powder, yield: 49.8%.
1HNMR(600MHz,DMSO)δ8.10(d,
J=2.6Hz,1H),7.89(dd,
J=9.1,2.6Hz,1H),7.51(d,
J=9.2Hz,1H),4.73(h,
J=6.0Hz,1H),2.49(s,3H),1.71(dd,
J=21.8,6.7Hz,2H),1.34(d,
J=6.1Hz,3H),0.97(d,
J=7.4Hz,3H).
(7) 5-methyl isophthalic acid-(3-cyano group-4-n-pentyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM07)
The crystallization of white cotton like, yield: 70.0%.
1HNMR(600MHz,DMSO)δ8.08(d,
J=2.6Hz,1H),7.89(dd,
J=9.0,2.6Hz,1H),7.47(d,
J=9.1Hz,1H),4.24(t,
J=6.4Hz,2H),2.49(s,3H),1.84–1.73(m,2H),1.45(dt,
J=14.4,7.0Hz,2H),1.37(dt,
J=14.4,7.1Hz,2H),0.91(t,
J=7.2Hz,3H).
(8) 5-methyl isophthalic acid-(3-cyano group-4-isopentyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM08)
Off-white powder, yield: 46.5%.
1HNMR(600MHz,DMSO)δ8.09(d,
J=2.6Hz,1H),7.90(dd,
J=9.0,2.6Hz,1H),7.50(d,
J=9.1Hz,1H),4.27(t,
J=6.5Hz,2H),2.49(s,3H),1.84(dd,
J=13.3,6.7Hz,1H),1.70(q,
J=6.6Hz,2H),0.97(d,
J=6.6Hz,6H).
(9) 5-methyl isophthalic acid-(the secondary pentyloxy of 3-cyano group-4-) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM09)
Off-white powder, yield: 25.9%.
1HNMR(600MHz,DMSO)δ8.05(d,
J=2.5Hz,1H),7.85(dd,
J=9.0,2.5Hz,1H),7.49(d,
J=9.2Hz,1H),4.81–4.74(m,1H),2.51(s,3H),1.76–1.68(m,1H),1.66–1.59(m,1H),1.52–1.36(m,2H),1.33(d,
J=6.0Hz,3H),0.93(t,
J=7.4Hz,3H).
(10) 5-methyl isophthalic acid-(3-cyano group-4-oxygen base in positive heptan) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM10)
Off-white powder, yield 39.6:%.
1HNMR(600MHz,DMSO)δ8.09(d,
J=2.6Hz,1H),7.90(dd,
J=9.0,2.6Hz,1H),7.48(d,
J=9.1Hz,1H),4.24(t,
J=6.4Hz,2H),2.49(s,3H),1.83–1.73(m,2H),1.51–1.41(m,2H),1.39–1.23(m,6H),0.87(t,
J=6.9Hz,3H).
(11) 5-methyl isophthalic acid-(3-cyano group-4-n-octyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM11)
Off-white powder, yield 49.2:%.
1HNMR(600MHz,DMSO)δ8.05(d,
J=2.5Hz,1H),7.86(dd,
J=9.0,2.4Hz,1H),7.45(d,
J=9.2Hz,1H),4.23(t,
J=6.4Hz,2H),2.49(s,3H),1.82–1.73(m,2H),1.50–1.42(m,2H),1.38–1.22(m,8H),0.86(t,
J=6.9Hz,3H).
(12) 5-methyl isophthalic acid-(3-cyano group-4-benzyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM12)
Off-white powder, yield: 85.5%.
1HNMR(600MHz,DMSO)δ8.12(d,
J=2.6Hz,1H),7.92(dd,
J=9.0,2.6Hz,1H),7.57(d,
J=9.1Hz,1H),7.52(d,
J=7.4Hz,2H),7.45(t,
J=7.6Hz,2H),7.39(t,
J=7.3Hz,1H),5.40(s,2H),2.50(s,3H).
(13) 5-methyl isophthalic acid-(3-cyano group-4-(4-chlorine) benzyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM13)
Off-white powder, yield: 87.4%.
1HNMR(600MHz,DMSO)δ8.14(d,
J=2.6Hz,1H),7.94(dd,
J=9.0,2.6Hz,1H),7.54(dt,
J=16.7,7.7Hz,5H),5.40(s,2H),2.50(s,3H).
(14) 5-methyl isophthalic acid-(3-cyano group-4-(4-cyano group) benzyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM14)
Off-white powder, yield: 65.4%.
1HNMR(600MHz,DMSO)δ8.16(d,
J=2.6Hz,1H),7.94(d,
J=8.3Hz,3H),7.71(d,
J=8.2Hz,2H),7.54(d,
J=9.1Hz,1H),5.52(s,2H),2.50(s,3H).
(15) 5-methyl isophthalic acid-(3-cyano group-4-methoxyethoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM15)
Faint yellow plate crystal, yield: 66.1%.
(16) 5-methyl isophthalic acid-(3-cyano group-4-allyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM16)
Off-white powder, yield: 75.2%.
(17) 5-methyl isophthalic acid-(3-cyano group-4-cyclopentyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM17)
Off-white powder, yield: 48.5%.
(18) 5-methyl isophthalic acid-(3-cyano group-4-(4-methoxyl group) benzyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM18)
White flaky crystals, yield 80.2:%.
1HNMR(600MHz,DMSO)δ8.07(d,
J=2.6Hz,1H),7.88(dd,
J=9.0,2.6Hz,1H),7.56(d,
J=9.2Hz,1H),7.45(d,
J=8.6Hz,2H),7.00(d,
J=8.6Hz,2H),5.30(s,2H),3.77(s,3H),2.49(s,3H).
Embodiment 9
2-alkoxyl group-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene
Salzburg vitriol (89 μm of ol) is added, vitamins C (89 μm of ol), ethanol (10mL) and water (10mL) in reaction flask, stirred at ambient temperature 15min, add 5-azido--2-alkoxy benzene formonitrile HCN (742 μm of ol) and 4-ethynyl pyridine hydrochloride (1110 μm of ol) again, microwave reaction 8min at 50 DEG C, react completely, remove the solvent of about half under reduced pressure, thin up, suction filtration, drying, crude product is separated (ethyl acetate: sherwood oil=1:3 ~ 1:1) through post and obtains sterling.
(1) 2-methoxyl group-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP01)
Purple powder, yield: 39.0%.
1HNMR(600MHz,DMSO)δ9.51(s,1H),8.71(s,2H),8.36(d,
J=2.7Hz,1H),8.27(dd,
J=9.1,2.7Hz,1H),7.87(d,
J=4.9Hz,2H),7.53(d,
J=9.2Hz,1H),4.02(s,3H).
(2) 2-positive propoxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP02)
Off-white powder, yield: 41.2%.
1HNMR(600MHz,DMSO)δ9.50(s,1H),8.70(d,
J=4.6Hz,2H),8.34(d,
J=2.7Hz,1H),8.23(dd,
J=9.1,2.7Hz,1H),7.86(d,
J=5.9Hz,2H),7.52(d,
J=9.2Hz,1H),4.21(t,
J=6.4Hz,2H),1.87–1.75(m,2H),1.03(t,
J=7.4Hz,3H).
(3) 2-isopropoxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP03)
Off-white powder, yield: 57.5%.
1HNMR(600MHz,DMSO)δ9.50(s,1H),8.73(s,2H),8.33(d,
J=2.2Hz,1H),8.21(dd,
J=9.1,2.2Hz,1H),7.87(s,2H),7.56(d,
J=9.2Hz,1H),4.91(dq,
J=11.1,5.6Hz,1H),1.37(d,
J=5.9Hz,6H).
(4) 2-n-butoxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP04)
Yellow powder, yield: 80.4%.
1HNMR(600MHz,DMSO)δ9.50(s,1H),8.33(d,
J=2.7Hz,1H),8.22(dd,
J=9.1,2.7Hz,1H),8.10(s,1H),7.52(d,
J=9.2Hz,1H),4.24(t,
J=6.4Hz,2H),1.83–1.73(m,2H),1.54–1.43(m,2H),0.97(t,
J=7.4Hz,3H).
(5) 2-isobutoxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP05)
Off-white powder, yield: 49.7%.
1HNMR(600MHz,DMSO)δ9.51(s,1H),8.70(d,
J=4.6Hz,2H),8.35(d,
J=2.7Hz,1H),8.28–8.14(m,1H),7.86(d,
J=6.0Hz,2H),7.52(d,
J=9.2Hz,1H),4.03(d,
J=6.5Hz,2H),2.11(dt,
J=13.3,6.6Hz,1H),1.04(d,
J=6.7Hz,6H).
(6) 2-sec-butoxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP06)
Yellow powder, yield: 38.5%.
1HNMR(600MHz,DMSO)δ9.50(s,1H),8.77(s,1H),8.33(d,
J=2.8Hz,1H),8.20(dd,
J=9.2,2.8Hz,1H),7.89(s,2H),7.55(d,
J=9.3Hz,1H),4.79–4.63(m,1H),1.72(qd,
J=13.5,5.8Hz,2H),1.33(d,
J=6.1Hz,3H),0.97(d,
J=7.4Hz,3H).
(7) 2-n-pentyloxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP07)
Off-white powder, yield: 55.0%.
1HNMR(600MHz,DMSO)δ9.50(s,1H),8.76(s,2H),8.34(d,
J=2.7Hz,1H),8.23(dd,
J=9.1,2.7Hz,1H),7.88(s,2H),7.52(d,
J=9.2Hz,1H),4.24(t,
J=6.5Hz,2H),1.84–1.75(m,2H),1.50–1.41(m,2H),1.38(dd,
J=14.8,7.3Hz,2H),0.92(t,
J=7.2Hz,3H).
(8) 2-isopentyloxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP08)
Off-white powder, yield: 29.7%.
1HNMR(600MHz,DMSO)δ9.53(s,1H),8.76(s,1H),8.33(s,1H),8.22(d,
J=8.8Hz,1H),7.54(d,
J=9.1Hz,1H),4.27(t,
J=6.4Hz,2H),1.84(dt,
J=13.2,6.7Hz,1H),1.70(dd,
J=13.0,6.4Hz,2H),0.97(d,
J=6.6Hz,6H).
(9) the secondary pentyloxy-5-of 2-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP09)
Off-white powder, yield: 48.8%.
(10) 2-oxygen base in positive heptan-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP10)
Pale yellow powder, yield: 48.0%.
(11) 2-n-octyloxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP11)
Off-white powder, yield: 54.0%.
(12) 2-benzyloxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP12)
Off-white powder, yield: 37.8%.
1HNMR(600MHz,DMSO)δ9.51(s,1H),8.74(s,2H),8.38(d,
J=2.7Hz,1H),8.25(dd,
J=9.1,2.7Hz,1H),7.87(s,2H),7.63(d,
J=9.2Hz,1H),7.52(d,
J=7.3Hz,2H),7.45(t,
J=7.6Hz,2H),7.39(t,
J=7.3Hz,1H),5.41(s,2H).
(13) 2-(4-chlorine) benzyloxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP13)
Off-white powder, yield: 49.2%.
1HNMR(600MHz,DMSO)δ9.51(s,1H),8.70(s,2H),8.38(d,
J=2.7Hz,1H),8.26(dd,
J=9.1,2.7Hz,1H),7.86(d,
J=5.0Hz,2H),7.61(d,
J=9.2Hz,1H),7.53(q,
J=8.6Hz,4H),5.40(s,2H).
(14) 2-(4-cyano group) benzyloxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP14)
Off-white powder, yield: 31.0%.
(15) 2-methoxyethoxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP15)
Off-white powder, yield: 64.8%.
1HNMR(600MHz,DMSO)δ9.51(s,1H),8.70(s,2H),8.35(d,
J=2.7Hz,1H),8.23(dd,
J=9.1,2.7Hz,1H),7.86(d,
J=5.7Hz,2H),7.54(d,
J=9.2Hz,1H),4.44–4.34(m,2H),3.80–3.70(m,2H),3.36(s,3H).
(16) 2-allyl group-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP16)
Off-white powder, yield: 65.0%.Purple powder, yield: %.
1HNMR(600MHz,DMSO)δ9.51(s,1H),8.70(d,
J=3.4Hz,2H),8.37(d,
J=2.7Hz,1H),8.24(dd,
J=9.1,2.7Hz,1H),7.86(d,
J=5.8Hz,2H),7.53(d,
J=9.2Hz,1H),6.10(ddd,
J=22.3,10.4,5.1Hz,1H),5.50(dd,
J=17.3,1.6Hz,1H),5.36(dd,
J=10.6,1.3Hz,1H),4.86(d,
J=5.1Hz,2H).
(17) 2-cyclopentyloxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP17)
Off-white powder, yield: 55.0%.
1HNMR(600MHz,DMSO)δ9.94(s,1H),9.57(s,1H),8.31(d,
J=2.3Hz,1H),8.21(s,1H),7.52(d,
J=9.2Hz,1H),5.12(t,
J=5.7Hz,1H),2.01(dt,
J=11.7,5.9Hz,2H),1.77(dd,
J=15.3,8.2Hz,4H),1.69–1.60(m,2H).
(18) 2-base-5-(4-(pyridin-4-yl)-1 just
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP18)
Off-white powder, yield: 58.2%.
(19) 2-ring oxygen base-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP19)
Off-white powder, yield: 50.8%.
1HNMR(600MHz,DMSO)δ9.50(s,1H),8.82(s,2H),8.33(d,
J=2.7Hz,1H),8.20(dd,
J=9.2,2.7Hz,1H),7.91(s,2H),7.58(d,
J=9.3Hz,1H),4.72(m,1H),1.94(m,2H),1.80–1.69(m,2H),1.60(m,2H),1.55–1.34(m,4H).
The xanthine oxidase inhibitory activity research of embodiment 9 target compound
(1) test materials
Reagent: XOD (frombovin, Sigma), xanthine, potassium primary phosphate, sodium hydroxide.
Instrument: electronic analytical balance (AR1140 type), electric-heated thermostatic water bath (DK-98-1 type), UV2100 type UV, visible light spectrophotometer.
(2) experimental technique
The potassium phosphate buffer of reaction diluent: 50mM, pH value 7.4.
Sample preparation: the sample accurately taking 10 μm of mol, the DMSO adding 100 μ L dissolves, and the PBS then adding 900ml obtains the mother liquor of 10mM.
The preparation of xanthine substrate: accurately take 9.127mg xanthine, adds a small amount of NaOH solution and dissolves, then add PBS solution and be diluted to 100mL constant volume (every day now joins).
Experimental procedure: add XOD (reaction density 1.4U/L), test medicine (positive drug employing allopurinol) in reaction system successively, 25 DEG C hatch 15min after add xanthine substrate (reaction density 86 μMs), reaction 60min after survey 294nm absorbance.Each sample parallel operates 3 times, records speed of reaction respectively, the inhibiting rate of calculation sample of averaging.
Blank group does not add XOD, adds the PBS of volume same with sample, and the change of record absorbancy is as blank.
According to following formulae discovery sample to the inhibiting rate of XOD:
A in formula
sample, A
cloudy, A
sample is empty, A
cloudy empty: the absorption peak representing sample, blank, XOD reference substance and enzyme reference substance respectively.Test result is in table 1.
The inhibit activities of table 1ZTF series under 28 μMs
| Sample number into spectrum | Inhibitor |
| ZTF01 | 26.7% |
| ZTF02 | 21.7% |
| ZTF03 | 75.2% |
| ZTF04 | 81.4% |
| ZTF05 | 82.3% |
| ZTF06 | 68.6% |
| ZTF07 | 83.6% |
| ZTF08 | 88.8% |
| ZTF10 | 84.1% |
| ZTF11 | 85.6% |
| ZTF12 | 94.0% |
| ZTF13 | 68.6% |
| ZTF14 | 67.2% |
| ZTF15 | 31.2% |
| ZTM01 | -9.6% |
| ZTM02 | -1.5% |
| ZTM03 | 19.1% |
| ZTM04 | 25.8% |
| ZTM05 | 36.1% |
| ZTM06 | 31.4% |
| ZTM07 | 26.4% |
| ZTM08 | 47.8% |
| ZTM09 | 42.1% |
| ZTM10 | 28.2% |
| ZTM11 | 26.0% |
| ZTM12 | 24.1% |
| ZTM13 | 26.5% |
| ZTM14 | 26.7% |
| ZTM15 | 10.6% |
| ZTM16 | 24.8% |
| ZTM17 | 13.6% |
| ZTM18 | 27.6% |
| ZTM19 | 7.2% |
| ZTP01 | 58.3% |
| ZTP02 | 1.5% |
| ZTP03 | 74.3% |
| ZTP04 | 75.6% |
| ZTP05 | 5.9% |
| ZTP08 | 81.3% |
| ZTP10 | 54.9% |
| ZTP15 | 19.9% |
| ZTP16 | -3.5% |
| ZTP17 | 86.6% |
| ZTP18 | 67.1% |
| Allopurinol | 97.3% |
Claims (7)
1. a 1-substituted-phenyl-1
h-1,2,3-triazoles compounds, is characterized in that: this compound is the such as compound shown in formula I, general formula II or its pharmaceutically acceptable salt, hydrate or solvate;
Wherein:
Each R1 is independently alkyl, a 3-10 carbon atom cycloalkyl, allyl group, methoxyethyl, benzyl, the substituted benzyl of 1-10 carbon; Substituted benzyl can be to halogeno-benzyl, to cyanobenzyls, to alkoxybenzyl;
Each R2 is independently H or methyl;
Each R3 is independently H or ethyl.
2. 1-substituted-phenyl-1 according to claim 1
h-1,2,3-triazoles compounds, is characterized in that: the compound of described formula I be following any one:
1-(3-cyano group-4-methoxyl group) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF01);
1-(3-cyano group-4-positive propoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF02);
1-(3-cyano group-4-isopropoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF03);
1-(3-cyano group-4-n-butoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF04);
1-(3-cyano-4-isobutoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF05);
1-(3-cyano group-4-sec-butoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF06);
1-(3-cyano group-4-n-pentyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF07);
1-(3-cyano group-4-isopentyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF08);
1-(the secondary pentyloxy of 3-cyano group-4-) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF09);
1-(3-cyano group-4-oxygen base in positive heptan) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF10);
1-(3-cyano group-4-n-octyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF11);
1-(3-cyano group-4-benzyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF12);
1-[3-cyano group-4-(4-chlorine) benzyloxy] phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF13);
1-[3-cyano group-4-(4-cyano group) benzyloxy] phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF14);
1-(3-cyano group-4-methoxyethoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF15);
1-(3-cyano group-4-allyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF16);
1-(3-cyano group-4-cyclopentyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF17);
1-[3-cyano group-4-(4-methoxyl group) benzyloxy] phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF18);
1-(3-cyano group-4-oxygen base just) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF19);
1-(3-cyano group-4-ring oxygen base) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTF20);
5-methyl isophthalic acid-(3-cyano group-4-methoxyl group) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM01);
5-methyl isophthalic acid-(3-cyano group-4-positive propoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM02);
5-methyl isophthalic acid-(3-cyano group-4-isopropoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM03);
5-methyl isophthalic acid-(3-cyano group-4-n-butoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM04);
5-methyl isophthalic acid-(3-cyano-4-isobutoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM05);
5-methyl isophthalic acid-(3-cyano group-4-sec-butoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM06);
5-methyl isophthalic acid-(3-cyano group-4-n-pentyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM07);
5-methyl isophthalic acid-(3-cyano group-4-isopentyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM08);
5-methyl isophthalic acid-(the secondary pentyloxy of 3-cyano group-4-) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM09);
5-methyl isophthalic acid-(3-cyano group-4-oxygen base in positive heptan) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM10);
5-methyl isophthalic acid-(3-cyano group-4-n-octyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM11);
5-methyl isophthalic acid-(3-cyano group-4-benzyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM12);
5-methyl isophthalic acid-[3-cyano group-4-(4-chlorine) benzyloxy] phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM13);
5-methyl isophthalic acid-[3-cyano group-4-(4-cyano group) benzyloxy] phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM14);
5-methyl isophthalic acid-(3-cyano group-4-methoxyethoxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM15);
5-methyl isophthalic acid-(3-cyano group-4-allyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM16);
5-methyl isophthalic acid-(3-cyano group-4-cyclopentyloxy) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM17);
5-methyl isophthalic acid-[3-cyano group-4-(4-methoxyl group) benzyloxy] phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM18);
5-methyl isophthalic acid-(3-cyano group-4-oxygen base just) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM19);
5-methyl isophthalic acid-(3-cyano group-4-ring oxygen base) phenyl-1
h-1,2,3-triazoles-4-formic acid (ZTM20).
3. 1-substituted-phenyl-1 according to claim 1
h-1,2,3-triazoles compounds, is characterized in that: the compound of described general formula II be following any one:
2-methoxyl group-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP01);
2-positive propoxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP01);
2-isopropoxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP03);
2-n-butoxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP04);
2-isobutoxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP05);
2-sec-butoxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP06);
2-n-pentyloxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP7);
2-isopentyloxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP08);
Secondary pentyloxy-the 5-of 2-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP09);
2-oxygen base in positive heptan-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP10);
2-n-octyloxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP11);
2-benzyloxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP12);
2-(4-chlorine) benzyloxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP13);
2-(4-cyano group) benzyloxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP14);
2-methoxyethoxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP15);
2-allyloxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP16);
2-cyclopentyloxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP17);
2-(4-methoxyl group) benzyloxy-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP8);
2-is oxygen base-5-(4-(pyridin-4-yl)-1 just
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP19);
2-ring is oxygen base-5-(4-(pyridin-4-yl)-1
h-1,2,3-tri-miaow-1-base) cyanobenzene (ZTP20).
4. a medicinal compositions, is characterized in that: comprise compound, its pharmacy acceptable salt, hydrate or the solvate of claim 1-3 described in any one and pharmaceutically acceptable carrier.
5. a preparation method for compound as claimed in claim 1, is characterized in that:
The preparation of compound shown in formula I, concrete steps are:
(1) take salicylonitrile as starting raw material, through nitrated, alkylation, reduction, diazotization obtains important intermediate 5-azido--2-alkoxy benzene formonitrile HCN;
(2) 5-azido--2-alkoxy benzene formonitrile HCN and ethyl propiolate are through Husigen cycloaddition reaction, then are hydrolyzed, and obtain R
2for the compound of H atom;
(3) 5-amino-2-alkoxy benzene formonitrile HCN and diethyl malonate are through ring-closure reaction, then are hydrolyzed, and obtain R
2for the compound of methyl;
The preparation of compound shown in general formula II, concrete steps are:
(1) take salicylonitrile as starting raw material, through nitrated, alkylation, reduction, diazotization obtains important intermediate 5-azido--2-alkoxy benzene formonitrile HCN;
(2) 5-azido--2-alkoxy benzene formonitrile HCN and 4-ethynyl pyridine hydrochloride are through Husigen cycloaddition reaction, obtain the compound shown in general formula II.
6. a 1-substituted-phenyl-1 as claimed in claim 1
h-1,2,3-triazoles compounds is preparing the application in anti-gout drugs.
7. one according to claim 6 1-substituted-phenyl-1 as claimed in claim 1
h-1,2,3-triazoles compounds is preparing the application in anti-gout drugs, it is characterized in that: described 1-substituted-phenyl-1
h-1,2,3-triazoles compounds is compound, its pharmacy acceptable salt, hydrate or the solvate of claim 1-3 described in any one or medicinal compositions according to claim 4.
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