CN105936633B - 5-（3- isopropyl benzoisoxazoles）Pyrazine -2- amine and preparation method thereof - Google Patents
5-（3- isopropyl benzoisoxazoles）Pyrazine -2- amine and preparation method thereof Download PDFInfo
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/80—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2
Abstract
The invention discloses 5-（3- isopropyl benzoisoxazoles）Pyrazine -2- amine and preparation method thereof.The 5-（3- isopropyl benzoisoxazoles）The structural formula such as formula of pyrazine -2- amine（I）It is shown.The compound is a kind of new Benzisoxazole compound, provides a kind of new germ killing drugs for the mankind, while further having widened the research field of Benzisoxazole compound.Also, the reaction gross production rate for preparing the compound is high, simple for process, is adapted to industrialized production.
Description
Technical field
The present invention relates to compound synthesis technical fields, and in particular, to Benzisoxazole compound, more specifically,
It is related to 5- (3- isopropyls benzoisoxazole) pyrazine -2- amine and preparation method thereof.
Background technology
Isoxazole group is very important drug effect functional group, and derivative has multiple biological activities, there are many
Drug containing isoxazole functional group successfully lists.Isoxazole group, which is introduced into certain bioactive molecules, can significantly improve it
Antibacterial activity.
Isoxazole and benzoisoxazole and its derivative are a kind of important heterocyclic compounds, it is not only in organic synthesis
Important composition-factor and intermediate, while also have antibacterial, bactericidal effect.Such as 3- (the 2,4- dichloros of intelligent et al. the synthesis of Ningguo
Phenyl) 11 kinds of disubstituted isoxazoline compounds of 3,5- such as -5- (4- pyridyl groups) -2,3- isoxazolines to peanut foxiness,
7 kinds of fungies such as apple wheel line, tomato early epidemic, gibberella saubinetii, Phytophthora capsici, rape sclerotium, rice banded sclerotial blight have good preventive effect,
5- (furans-the 2) -3- phenyl-isoxazoles azoles of Chen Gang et al. synthesis has certain inhibiting effect, Zhang Cunyan to sulfate reducing bacteria
Et al. synthesis 15 kinds of Xin Xing isoxazole derivants to staphylococcus aureus, Sarcina lutea, Pseudomonas aeruginosa and
Klebsiella pneumoniae has certain antibacterial activity, 7 with the pyridine heterocycle kind isoxazole derivatives pair of Zhang Zheng et al. synthesis
Melon Powdery Mildew has certain preventive effect, etc..In addition to this , isoxazole compounds are alternatively arranged as antipsychotics and weeding
Agent also has osteoporosis certain curative effect.
Invention content
The purpose of the invention is to find the heterocyclic compound with more preferable sterilization, antibacterial activity, and further widen
The research field of benzisoxazole compounds provides 5- (3- isopropyls benzoisoxazole) pyrazine -2- amine.
It is a further object to provide the preparation methods of 5- (3- isopropyls benzoisoxazole) pyrazine -2- amine.
To achieve the goals above, the present invention is achieved by the following technical programs：
5- (3- isopropyls benzoisoxazole) pyrazine -2- amine, shown in structural formula such as formula (I)：
The preparation method of formula (I) described 5- (3- isopropyls benzoisoxazole) pyrazine -2- amine, includes the following steps：
The fluoro- 4- bromobenzoic acids of S1.2- and N, O- dimethyl hydroxylamine hydrochloride, dichloromethane, I-hydroxybenzotriazole, 1- second
Base -3 (3- dimethyl propylamines) carbodiimide, n,N-diisopropylethylamine are reacted at room temperature, and reaction is quenched after the completion of reaction, removes
The bromo- N- methoxy-. N-methyls benzamides of the fluoro- 4- of 2- are obtained after removing solvent, extraction, concentration, column chromatography；
S2. be added into the bromo- N- methoxy-. N-methyls benzamides of the fluoro- 4- of 2- tetrahydrofuran and then nitrogen protection ,-
Isopropyl magnesium bromide reaction is added under the conditions of 78 DEG C, isopropyl is obtained after reaction, extraction, concentration, column chromatography is quenched after the completion of reaction
The fluoro- 4- bromobenzophenones of base -2-；
S3. methanol, hydroxylamine hydrochloride, potassium acetate are added into the fluoro- 4- bromobenzophenones of isopropyl -2- and carries out back flow reaction, instead
The fluoro- 4- bromobenzenes first oximes of isopropyl -2- are obtained after should reaction, extraction, concentration, column chromatography being quenched after the completion；
S4. acetonitrile, 1,8- diazabicylos-bicyclic (5,4,0) -7- are added into the fluoro- 4- bromobenzenes first oximes of isopropyl -2-
Hendecene is reacted at 80 DEG C, and column chromatography for separation obtains 3- isopropyl -6- bromine benzoisoxazoles；
S5. 5- amido pyrazine -2- boric acid, cesium fluoride, palladium catalyst Pd are added into 3- isopropyl -6- bromine benzoisoxazoles
(pddf)Cl2, dioxane, 50 DEG C reaction, filtering, concentration, column chromatography obtain 5- (3- isopropyls benzoisoxazole) pyrazine -2-
Amine.
Preferably, the fluoro- 4- bromobenzoic acids of 2- in step S1：N, O- dimethyl hydroxylamine hydrochloride：I-hydroxybenzotriazole：1- second
Base -3 (3- dimethyl propylamines) carbodiimide：The molar ratio of N, N- diisopropylethylamine is 228.3:274:457:457:457.
Preferably, the bromo- N- methoxy-. N-methyls benzamides of the fluoro- 4- of 2- in step S2：The molar ratio of isopropyl magnesium bromide
It is 118.8:200.
Preferably, the fluoro- 4- bromobenzophenones of isopropyl -2- in step S3：Hydroxylamine hydrochloride：The molar ratio of potassium acetate is 31.6:
94.8:157.5。
Preferably, the fluoro- 4- bromobenzenes first oximes of isopropyl -2- described in step S4：1,8- diazabicylo-bicyclic (5,4,0)-
The molar ratio of 7- hendecenes is 23.84:95.36.
Preferably, 3- isopropyls -6- bromine benzoisoxazoles described in step S5：5- amido pyrazine -2- boric acid：Cesium fluoride：Palladium
Catalyst Pd (pddf) Cl2Molar ratio be 1:3:2:2.
Preferably, extraction described in S1, S2, S3 is to be extracted with ethyl acetate 3 times, and each dosage of ethyl acetate is
500ml。
Preferably, S1, S2, S3, S4 utilize the Disappearance Scenarios of TLC tracking reaction raw materials.
Application of formula (I) described 5- (3- isopropyls benzoisoxazole) pyrazine -2- amine in preparing germ killing drugs.
Preferably, the germ killing drugs are to kill peanut Cercospora bacteria, Botryosphaeria berengeriana f. sp, tomato early blight bacterium, wheat
Gibberellic hypha, potato late blight bacterium, Rhizoctonia solani Kuhn drug.
Preferably, 100ml H are added after the completion of step S1 reactions2Reaction is quenched in O.
Preferably, 60ml saturated ammonium chlorides are added after the completion of step S2 reactions and reaction is quenched.
Preferably, 60ml H are added after the completion of step S3 reactions2Reaction is quenched in O.
Compared with prior art, the present invention has the advantages that：
5- (3- isopropyls benzoisoxazole) pyrazine -2- amine provided by the invention is a kind of new benzo-isoxazole chemical combination
Object provides a kind of new germ killing drugs for the mankind, while further having widened the research field of Benzisoxazole compound.
Also, the reaction gross production rate for preparing the compound is high, simple for process, is adapted to industrialized production.
Specific implementation mode
The present invention is made with reference to specific embodiment and further being elaborated, the embodiment is served only for explaining this
Invention, is not intended to limit the scope of the present invention.Test method used in following embodiments is normal unless otherwise specified
Rule method；Used material, reagent etc., unless otherwise specified, for the reagent and material commercially obtained.
Embodiment 1
A kind of preparation method of 5- (3- isopropyls benzoisoxazole) pyrazine -2- amine, concrete thought see below row reaction equation：
1 is the fluoro- 4- bromobenzoic acids of 2- in reaction equation；2 be N, O- dimethyl hydroxylamine hydrochlorides；3 be the bromo- N- methoxies of the fluoro- 4- of 2-
Base-N-methyl-benzamide；4 be the fluoro- 4- bromobenzophenones of isopropyl -2-；5 be the fluoro- 4- bromobenzenes first oximes of isopropyl -2-；6 is different for 3-
Propyl -6- bromine benzoisoxazoles；7 be 5- (3- isopropyls benzoisoxazole) pyrazine -2- amine.
Specific preparation process is as follows：
The synthesis of the bromo- N- methoxy-. N-methyls benzamides (3) of the fluoro- 4- of S1.2-：In 2L single necked round bottom flask successively
Fluoro- 4- bromobenzoic acids (1) 50g (228.3mmol) of 2-, N, O- dimethyl hydroxylamine hydrochloride (2) 26g (274mmol), dichloro is added
Methane 500ml, HOBT 70g (457mmol), EDCI 52.5g (457mmol), DIEA 59g (457mmol) are stirred at room temperature
Reaction tracks the disappearance of reaction raw materials using TLC.100ml H are added after the completion of reaction2Reaction is quenched in O, and it is molten to remove dichloromethane
Agent, remaining aqueous layer with ethyl acetate extraction three times (each 500ml), collect ethyl acetate, crude product are concentrated to give after organic phase drying,
The bromo- N- methoxy-. N-methyls benzamides (3) (white solid, 50.74g) of the fluoro- 4- of compound 2- are obtained through column chromatography for separation,
Yield is 85%.LC-MS:M/Z=262.1 [M+H]+.
S2. the synthesis of the fluoro- 4- bromobenzophenones (4) of isopropyl -2-：By the bromo- N- methoxy-. N-methyls benzene of the fluoro- 4- of above-mentioned 2-
Formamide (3) 31g (118.8mmol) is put into reaction bulb, the anhydrous THF of 150ml is added, then in nitrogen protection, -78 DEG C of conditions
Under, it is slowly added into the tetrahydrofuran solution of a concentration of 2M isopropyl magnesium bromides of 100mL.After reacting recovery to room temperature, continue to stir
Reaction is mixed, the disappearance of reaction raw materials is tracked using TLC.60ml saturated ammonium chlorides are added after the completion of reaction, reaction is quenched, then uses second
Acetoacetic ester extracts three times (each 200ml), collects ethyl acetate, crude product is concentrated to give after to be dried, column chromatography for separation obtains compound
The fluoro- 4- bromobenzophenones (4) (white solid, 23.1g) of isopropyl -2-, yield 79.2%.LC-MS:M/Z=245.1 [M+
H]+。
S3. the synthesis of the fluoro- 4- bromobenzenes first oximes (5) of isopropyl -2-：By the fluoro- 4- bromobenzophenones (4) of above-mentioned isopropyl -2-
7.7g (31.6mmol) is put into reaction bulb, sequentially adds methanol 150ml, hydroxylamine hydrochloride 6.59g (94.8mmol), potassium acetate
15.5g (157.5mmol), back flow reaction track the disappearance of reaction raw materials using TLC.60ml H are added after the completion of reaction2O quenches
It goes out reaction, is extracted with ethyl acetate (each 100ml) three times, collect ethyl acetate, crude product, column chromatography point are concentrated to give after to be dried
From the fluoro- 4- bromobenzenes first oximes (5) (white solid, 6.2g) of compound isopropyl -2-, yield 75.4%.
The synthesis of S4.3- isopropyl -6- bromines benzoisoxazoles (6)：By the fluoro- 4- bromobenzenes first oximes (5) of above-mentioned isopropyl -2-
6.2g (23.84mmol) is put into reaction bulb, sequentially adds acetonitrile 100ml, DBU13.8ml (95.36mmol), and 80 DEG C are reacted,
The disappearance of reaction raw materials is tracked using TLC.It is concentrated to give crude product after the completion of reaction, column chromatography for separation obtains compound 3- isopropyls-
6- bromines benzoisoxazole (6) (white solid, 4.6g), yield 80.6%.
The mass spectral results of 3- isopropyl -6- bromine benzoisoxazoles are：1H NMR(300MHz,DMSO):8.07 (d, J=
1.5Hz, 1H), 7.92 (d, J=8.4Hz, 1H), 7.54 (dd, J=8.4,1.6Hz, 1H), 3.43 (dt, J=13.9,
6.9Hz, 1H), 1.39 (d, J=6.9Hz, 6H) .LC-MS:M/Z=240.0 [M+H]+, tR=1.77 min.HPLC:98%
(214nm), 99% (254nm), tR=6.03min.
S5. above-mentioned 3- isopropyls -6- bromines benzoisoxazole (6) 239mg (1mmol) is put into reaction bulb, is sequentially added
5- amido pyrazine -2- boric acid 417mg (3mmol), cesium fluoride 304mg (2mmol), palladium catalyst Pd (pddf) Cl2 1.48g
(2mmol) and 20ml dioxane, 50 DEG C of reactions, the disappearance of reaction raw materials is tracked using TLC.Mixed liquor mistake after the completion of reaction
Filter, is concentrated to give crude product, and obtaining compound 5- (3- isopropyls benzoisoxazole) pyrazine -2- amine (7) through column chromatography for separation, (white is solid
Body, 80mg), yield 40%.
The mass spectral results of 5- (3- isopropyls benzoisoxazole) pyrazine -2- amine are：1H NMR(300MHz, CD3OD):
8.65 (d, J=1.3Hz, 1H), 8.42 (d, J=1.3Hz, 1H), 8.19 (s, 1H), 7.96-7.95 (m, 2H), 3.47 (dt, J
=14.0,7.0Hz, 1H), 1.50 (d, J=7.0Hz, 6H) .LC-MS:M/Z=255.1 [M+H]+, tR=
1.58min.HPLC:98% (214nm), 98% (254nm), tR=5.75min.
Embodiment 2
S1. fluoro- 4- bromobenzoic acids (1) 50g (228.3mmol) of 2-, N, O- bis- are sequentially added in 2L single necked round bottom flask
Methyl hydroxylamine hydrochloride (2) 26g (274mmol), dichloromethane 500ml, HOBT 70g (457mmol), EDCI 52.5g
(457mmol), TEA 46.2g (457mmol), is stirred to react at room temperature, and the disappearance of reaction raw materials is tracked using TLC.It has reacted
At rear addition 100ml H2Reaction is quenched in O, removes dichloromethane solvent, and remaining aqueous layer with ethyl acetate extraction is (each three times
500ml), ethyl acetate is collected, crude product is concentrated to give after organic phase drying, the bromo- N- of the fluoro- 4- of compound 2- is obtained through column chromatography for separation
Methoxy-. N-methyl benzamide (3) (white solid, 18.5g), yield 31%.
The present embodiment step S2~S4 is the same as embodiment 1.
Embodiment 3
S1. fluoro- 4- bromobenzoic acids (1) 50g (228.3mmol) of 2-, N, O- bis- are sequentially added in 2L single necked round bottom flask
Methyl hydroxylamine hydrochloride (2) 26g (274mmol), dichloromethane 500ml, HOBT 70g (457mmol), EDCI 52.5g
(457mmol), NMM 46.2g (457mmol), is stirred to react at room temperature, and the disappearance of reaction raw materials is tracked using TLC.It has reacted
At rear addition 100ml H2Reaction is quenched in O, removes dichloromethane solvent, and remaining aqueous layer with ethyl acetate extraction is (each three times
500ml), ethyl acetate is collected, crude product is concentrated to give after organic phase drying, the bromo- N- of the fluoro- 4- of compound 2- is obtained through column chromatography for separation
Methoxy-. N-methyl benzamide (3) (white solid, 13.7g), yield 23%.
The present embodiment step S2~S4 is the same as embodiment 1.
DIEA ratios TEA, NMM are more suitable for the reaction for step S1 it can be seen from embodiment 2 and 3, in S1 when with
DIEA is alkali, when dosage is 2 times of equivalents of compound (1), synthesized product Compound (3) yield highest, up to 85%.
Embodiment 4
The present embodiment step S1~S3 is the same as embodiment 1.
S4. by fluoro- 4- bromobenzenes first oxime (5) 6.2g (23.84mmol) the input reaction bulbs of above-mentioned isopropyl -2-, add successively
Enter acetonitrile 100ml, DBN11.8ml (95.36mmol), 80 DEG C of reactions track the disappearance of reaction raw materials using TLC.Reaction is completed
After be concentrated to give crude product, column chromatography for separation obtain compound 5- (3- isopropyls benzoisoxazole) pyrazine -2- amine (6) (white solid,
2.1g), yield 36.8%.
Embodiment 5
The present embodiment step S1~S3 is the same as embodiment 1.
S4. by fluoro- 4- bromobenzenes first oxime (5) 6.2g (23.84mmol) the input reaction bulbs of above-mentioned isopropyl -2-, add successively
Enter acetonitrile 100ml, DBU13.8ml (95.36mmol), 50 DEG C of reactions track the disappearance of reaction raw materials using TLC.Reaction is completed
After be concentrated to give crude product, column chromatography for separation obtain compound 5- (3- isopropyls benzoisoxazole) pyrazine -2- amine (6) (white solid,
1.7g), yield 29.8%.
By embodiment 4 and 5 it is found that DBU ratios DBN is more suitable for S4；S4 reacts ratio when using DBU as alkali under the conditions of 80 DEG C
Under the conditions of 50 DEG C, reaction yield higher；Therefore, step 4 selects DBU for alkali, and reaction temperature is 80 DEG C.
Embodiment 6
The present embodiment step S1~S4 is the same as embodiment 1.
S5. above-mentioned 3- isopropyls -6- bromines benzoisoxazole (6) 239mg (1mmol) is put into reaction bulb, is sequentially added
5- amido pyrazine -2- boric acid 417mg (3mmol), potassium carbonate 276mg (2mmol), palladium catalyst Pd (pddf) Cl2 1.48g
(2mmol) and 20ml dioxane, 50 DEG C of reactions, the disappearance of reaction raw materials is tracked using TLC.Mixed liquor mistake after the completion of reaction
Filter, is concentrated to give crude product, and obtaining compound 5- (3- isopropyls benzoisoxazole) pyrazine -2- amine (7) through column chromatography for separation, (white is solid
Body, 18mg), yield 9%.
Embodiment 7
The present embodiment step S1~S4 is the same as embodiment 1.
S5. above-mentioned 3- isopropyls -6- bromines benzoisoxazole (6) 239mg (1mmol) is put into reaction bulb, is sequentially added
5- amido pyrazine -2- boric acid 417mg (3mmol), cesium fluoride 304mg (2mmol), palladium catalyst Pd (PPh3)42.31g(2mmol)
With 20ml dioxane, 50 DEG C of reactions track the disappearance of reaction raw materials using TLC.Mixed liquor filters after the completion of reaction, is concentrated to give
Crude product obtains compound 5- (3- isopropyls benzoisoxazole) pyrazine -2- amine (7) (white solid, 32mg) through column chromatography for separation,
Yield is 16%.
Relative to potassium carbonate and palladium catalyst Pd (PPh known to embodiment 6,73)4, cesium fluoride and palladium catalyst Pd
(pddf)Cl2It is more suitable for making alkali and catalyst in S5.
Embodiment 8
Compound (7) Determination of Antibacterial Activity：Compound (7) sample concentration is 500mg/L, taking liquid 1mL, injects culture dish
It is interior, 9mLPSA culture mediums are added, 50mg/L drug containing tablets are made.Cultured beaten for reagent card punch is taken into diameter 5mm
Bacteria cake is put as in drug containing tablet per 3 pieces of ware is in equilateral triangle.Blank control is done with not adding medicine.By each processing in 24
It in ± 1 DEG C of incubator after culture 48h, measures each processing mycelia and extends diameter, and be compared with a control, calculating is opposite to inhibit percentage
Rate.Active graded index：A grades：More than or equal to 90%；B grades：70~90%；C grades：50~70%；D grades：Less than 50%.
The biological activity test of compound (7) the results are shown in Table 1.
The bactericidal activity of 1 compound of table (7)
From table 1 it follows that compound (7) to potato late blight bacterium, Rhizoctonia solani Kuhn, tomato early blight bacterium and
Fusarium graminearum has good inhibiting effect, wherein being up to 81.7% to the inhibiting rate of potato late blight bacterium.
Claims (10)
1.5- (3- isopropyls benzoisoxazole) pyrazine -2- amine, which is characterized in that shown in its structural formula such as formula (I)：
The preparation method of 5- described in claim 1 2. (3- isopropyls benzoisoxazole) pyrazine -2- amine, which is characterized in that including
Following steps：
The fluoro- 4- bromobenzoic acids of S1.2- and N, O- dimethyl hydroxylamine hydrochloride, dichloromethane, I-hydroxybenzotriazole, 1- ethyls -3
(3- dimethyl propylamines) carbodiimide, n,N-diisopropylethylamine are reacted at room temperature, and reaction is quenched after the completion of reaction, are removed molten
The bromo- N- methoxy-. N-methyls benzamides of the fluoro- 4- of 2- are obtained after agent, extraction, concentration, column chromatography；
S2. tetrahydrofuran and then nitrogen protection, -78 DEG C of items are added into the bromo- N- methoxy-. N-methyls benzamides of the fluoro- 4- of 2-
Isopropyl magnesium bromide reaction is added under part, isopropyl -2- is obtained after reaction, extraction, concentration, column chromatography is quenched after the completion of reaction
Fluoro- 4- bromobenzophenones；
S3. methanol, hydroxylamine hydrochloride, potassium acetate are added into the fluoro- 4- bromobenzophenones of isopropyl -2- and carries out back flow reaction, has reacted
The fluoro- 4- bromobenzenes first oximes of isopropyl -2- are obtained after reaction, extraction, concentration, column chromatography are quenched after；
S4. acetonitrile, 1,8- diazabicylos-bicyclic (5,4,0) -7- hendecenes are added into the fluoro- 4- bromobenzenes first oximes of isopropyl -2-
It is reacted at 80 DEG C, column chromatography for separation obtains 3- isopropyl -6- bromine benzoisoxazoles；
S5. 5- amido pyrazine -2- boric acid, cesium fluoride, palladium catalyst Pd are added into 3- isopropyl -6- bromine benzoisoxazoles
(pddf)Cl2, dioxane, 50 DEG C reaction, filtering, concentration, column chromatography obtain 5- (3- isopropyls benzoisoxazole) pyrazine -2-
Amine.
3. preparation method according to claim 2, which is characterized in that the fluoro- 4- bromobenzoic acids of 2- in step S1：N, O- diformazan
Base hydroxylamine hydrochloride：I-hydroxybenzotriazole：1- ethyls -3 (3- dimethyl propylamines) carbodiimide：N, N- diisopropylethylamine rub
You are than being 228.3:274:457:457:457.
4. preparation method according to claim 2, which is characterized in that the bromo- N- methoxyl groups-N- first of the fluoro- 4- of 2- in step S2
Yl-benzamide：The molar ratio of isopropyl magnesium bromide is 118.8:200.
5. preparation method according to claim 2, which is characterized in that the fluoro- 4- bromobenzophenones of isopropyl -2- in step S3：
Hydroxylamine hydrochloride：The molar ratio of potassium acetate is 31.6:94.8:157.5.
6. preparation method according to claim 2, which is characterized in that the fluoro- 4- bromobenzenes first of isopropyl -2- described in step S4
Oxime：The molar ratio of 1,8- diazabicylo-bicyclic (5,4,0) -7- hendecenes is 23.84:95.36.
7. preparation method according to claim 2, which is characterized in that 3- isopropyls -6- bromine benzisoxas Evil described in step S5
Azoles：5- amido pyrazine -2- boric acid：Cesium fluoride：Palladium catalyst Pd (pddf) Cl2Molar ratio be 1:3:2:2.
8. preparation method according to claim 2, which is characterized in that extraction is to use ethyl acetate described in S1, S2, S3
Extraction 3 times, each dosage of ethyl acetate are 500ml.
9. application of (the 3- isopropyls benzoisoxazole) pyrazine -2- amine of 5- described in claim 1 in preparing germ killing drugs.
10. application according to claim 9, which is characterized in that the germ killing drugs are to kill peanut Cercospora bacteria, apple
Target spot pathogen, tomato early blight bacterium, fusarium graminearum, potato late blight bacterium, Rhizoctonia solani Kuhn drug.
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| TW201141855A (en) * | 2010-04-27 | 2011-12-01 | Calcimedica Inc | Compounds that modulate intracellular calcium |
| CN104981247A (en) * | 2012-09-06 | 2015-10-14 | 普莱希科公司 | Compounds and methods for kinase modulation, and indications therefor |
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