Method for the synthesis of pyrimidines or theirs acid- additive salts

专利摘要:
The invention relates to heterocyclic compounds, in particular to the preparation of pyrimidines f-ly 2 VNHTfV Rl Ra R where or C 1 -C 4 -alkyl, P 2-C 1 C 4 -alkyl or C 3 Sb-cycloalkyl or RI and R2 is one of the residues (CHa ) 4 - or - (CHaJs-, Ra-H, R4-NHa-yl NH-OO-Rs, and P5-C1-C4-alkyl or perhalogenated Ci-Cz-alkyl, or their acid addition salts, exhibiting pesticidal activity. The goal is to detect more active compounds. The preparation is carried out by reacting chloropyrimidine with an amine to obtain compound f-ly (I), where R4 is NH2, if necessary, is converted into compound f-ly (I), where R4-NH -CO -R5, followed by isolation of the compound phla (I) in free form or in the form of an acid addition salt. Table 2 Table 2
公开号:SU1711672A3
申请号:SU884355955
申请日:1988-06-28
公开日:1992-02-07
发明作者:Кристинссон Хаукур；Кристиансен Одд
申请人:Циба-Гейги, Аг (Фирма)；
IPC主号:

专利说明:

The invention relates to a process for the preparation of new substituted 2,4-diamino-5-cyanopyrimidines of the general formula
N. sKl
R-KTT ™
 K2 R4
0)
where Ri is hydrogen or C1-C4-alkyl;
Ra means C- | -C4-alkyl or Cz-Ce-Cycloalkyl or RI and Ra together one of the residues ČSN) 4 - or - (CH2) s;
Ra is hydrogen;
R4 is one of the residues -NH2 or -NH-CO- Rs;
RS-C 1 -C 4 -alkyl, perhalogenated Ci-C 3 -alkyl, or their acid addition
salts exhibiting pesticidal activity.
 The purpose of the invention is to find new compounds exhibiting higher pesticidal activity.
Example 1. Preparation of the starting compound 2-chloro-4,6-diamino-5-cyanopyrimidine.
Combine the suspension from 50 g of crushed 2-chloro-4-amino-5-cyano-6-methylthiopyrimidine in 750 ml of dioxane and 250 ml of water at 0 ° C. Then a strong stream of chlorine is introduced into this suspension with stirring and without cooling. After about 20 minutes, a clear solution is obtained. After another 30 minutes, chlorine delivery is stopped and the contents are mixed for 1/2 hour.
ON VI
Yu

with
The reaction mixture was evaporated, the residue was shaken with 600 ml of ice-water and then filtered. The 2-chloro-4-amino-5-cyano-6-methylsulfonylpyrimidine obtained as a residue after filtration (mp. 253 ° C decomp.) In an amount of 46.4 g is mixed with 25 g of a 30% aqueous solution of ammonia and 1000 ml of acetonitrile at room temperature for 2 hours. After evaporation, the contents are shaken with water and filtered. Get the compound of the formula
H2N-Ag-C1
 ,
MH2
with t, pl. 260 ° C (compound 1.5).
Example 2. Preparation of 2-cyclopropylamino-4,6-diamino-5-cyanopyrimidine.
17 g of 2-chloro-4,6-diamino-5-cyanopyrimidine are suspended in 100 ml of acetonitrile. At. 14 g of cyclopropylamine is added to the suspension under stirring and refluxed for 12 hours. After cooling, the suspension is poured into ice / water, the resulting precipitate is filtered off and washed many times with water.
Get the compound of the formula

VNH-
N NH2
st.pl.2 9-251 ° C.
Example 3. Obtaining N.N-dimethyl M- (2-cyc.lopropylamino-4-amino-5-cyano pyrimidinyl-6) -formamidine.
3.7 g of dimethylformamide diethyl acetate are added dropwise to a solution containing 3.8 g of 2-cyclopropylamino-4,6-diamino-5-cyanopyrimidine in 1.00 ml of dioxane at 45-50 ° C. The reaction mixture is stirred at 45-50 ° C for 8 hours. After distillation of the solvent and recrystallization of the crude product from ethanol, a compound of the formula:
HuN-rrN pNH- l NeC-iL N
HU-CH-N (CH3) 2
M.p. 192-195 ° (compound 1.4).
Similarly, other compounds of formula (I) are prepared.
0
five
0
50
five
0
50
five
In tab. 1 shows the results of the preparation of the compounds; in tab. 2 - obtaining salts of compounds.
A compound of the formula ((), in which R4 is NH-CO R5, is usually prepared by acylation of a compound of formula (I), where R4 is NH2.
Preparation of 2-diethylamino-4-amino-5-cyano-6-isobutyramine pyrimidine.
To a solution of 10.3 g of 2-diethylamino-4,6-diamino-6-cyanopyrimidine in 90 ml of tetrahydrofuran was added 7 g of triethylamine. 8.5 g of isobutyric anhydride is added dropwise to this solution at 60 ° C. The reaction mixture is heated under reflux for 48 h, evaporated and the residue obtained is washed with diethyl ether. Get connection with so pl, 151-152 ° C (compound 1.3). Examples 4-15 show the activity of the compounds.
Example 4. Action against Musca domestica.
50 g of freshly prepared nutrient solution for the larvae are weighed into glasses. From a 1% acetone solution of the respective active substance, a certain amount is pipetted onto the nutrient solution in the beakers, so that an active substance concentration of 800 ppm is obtained. After stirring the substrate, the acetone is evaporated for at least 20 hours.
Then, the active substance at the indicated dilution is added to 25 daily Musca domestica in a glass ,. containing the nutrient substrate treated in this way. After the oculi larvae, the formed pupae are separated from the substrate by rinsing with water and kept in glass lids closed with mesh covers. The number of pupae washed into each vessel is counted (the toxic effect of the active substance on the development of the larvae). After 10 days, the number of flies developed from the pupae was determined.
Compounds 1I, 1.2.1.3.1.5-1.32, and 1.41-1.43 at the indicated concentration of active substance show activity (% mortality) of at least 50-60%.
Example 5. Action against Lucilia sericata.
To 9 ml of medium for dilution at 50 ° C, add 1 ml of 0.5% aqueous prepared preparation containing the active substance. About 30 freshly harvested Lucilia sericata larvae are added to the dilution medium and the insecticidal action is determined after 48 and 96 degree of destruction.
Compounds 1.1.1.2, .1.3,1.5-1.32 and 1.41- 1.43 show, at the indicated concentration of active substance, an activity (% killing) of at least 50-60%.
Example 6. Action against Lucilla cuprina.
Freshly laid eggs of the Llcllla cuprina meat fly are placed in a reaction vessel 30-50 eggs each, where they are previously mixed 4. ml of the nutrient medium with 1 ml of the active substance solution. After inoculation of the culture medium, the test vessels are covered with cotton swabs and kept in an incubator at 30 ° C for more than 4 days.
In the untreated medium, larvae about 1 cm long (third stage) develop at this point in time. If the substance is active, then the larvae are either dead or dying by this point in time. The test is carried out at an active substance concentration of 400 ppm. The resettlement is confirmed if the larvae from the environment migrate and die of starvation.
Compounds 1.1.1.2.1.3.1.5-1.32 and 1.41- 1.43 show at the indicated concentration of active substance an activity (% mortality) of at least 50-60%.
Example .7. Action against Aedes aegyptl.
To the surface of 150 ml of water, which is in the tank, so much 0.1% acetone solution of the active substance is pipetted to obtain a concentration of 800 ppm. After stripping the acetone, 30-40 2-day-old Aedes larvae are added to the tank. After 1, 2 and 5 days, mortality is determined.
Compounds 1.1,1.2,1.3,1.5-1.32 and t.41-143 show, at the indicated concentration of active substance, activity {% mortality) of at least 50-60%.
PRI me R 8. Insecticidal action. . Cotton plants grown in pots to a height of approximately 25 cm are sprayed with an aqueous emulsion of the active substance, in which the active substance is contained in a concentration of respectively 100. 200 and 400 ppm.
After the sprayed layer has dried on, the cotton plants are placed on Spodoptera littoralis or Metlothls virescens larvae at the third stage of development. The test was carried out at 24 ° C and a relative humidity of 60%. After two days, the mortality of the larvae was determined in%.
Efficiencies of 80-100% (mortality) are shown by compounds 1.1 and 1.2 at a concentration of 200 and 400 ppm relative to Spodoptera larvae. Compound 1.1 at a concentration of 100 ppm and compound 1.2 at a concentration of 400 ppm show 80-100% efficacy (mortality) in relation to HeHothls larvae.
PREMIER 9, Action against the Anthonomus grandis.
Two cotton plants grown in pots at the developmental stage of 6 leaves are sprayed with a ready-made aqueous wetting emulsion containing 400 ppm of the test substance, respectively. After the applied layer dries (approximately 1.5 hours), 10 adult beetles (Anthohomus grandis) are placed on each plant. Plastic cylinders, in which the upper opening is covered with a mesh, are then placed above the plants on which the beetles to be planted are planted in order to prevent their movement. The plants thus treated are kept at 25 ° C and approximately 60% air humidity. The assessment was carried out after 2.3, 4 and 5 days, based on the percentage mortality of the planted test beetles (% lying on the back), as well as (antiphidant effect) in relation to the untreated control beetles.
Compounds 1.1.1.2.1.3.1: 5-1.32 and 1.41- 1.43 show an efficacy of at least 50-60% (mortality) at the indicated concentrations of the active substance.
PRI eri 10. Action against ticks
a) Amblyomma hebraeum 50 nymphs are counted into glass tubes and dipped for 1-2 minutes in 2 ml of an aqueous emulsion containing 400 ppm of the test substance. Then the tubes are closed with cotton swabs and turned upside down so that the emulsion of the active substance can get onto the cotton wool.
The evaluation is carried out after 1 week. Two replications were performed for each experiment, b) Boophilus mictoplus (larvae).
At a similar dilution, as indicated in point a, the experiment was carried out with larvae taken from 20 sensitive or OP-resistant pieces. (Resistance refers to range compatibility).
Compounds Ns 1.1, 1.2, 1.3, 1.5-1.32 and 1.41-1.43 show, at the indicated concentrations of the active substance, efficacy (% mortality) of at least 50-60%.
Example 11. Insecticidal action against Nllaparvata lugens.
Rice plants are sprayed with a test solution containing 400 ppm of the mixture to be tested. After
the drying of the layer of a plant is infested with the nllahs nllaparvata lugens second or third. Two plants were taken for each test compound and for each test. Evaluation of the killing degree achieved in percent is carried out after 6 days. The test was carried out at 26 ° C and a relative humidity of 60%.
Compound 1.1 shows an 80-100% effect against the nymphs Nllaparvata lugens.
Example 12. Action against terrestrial insects Diabreotlca balteata.
Five shoots of maize, 1–3 cm in size, as well as twisted filter paper, are dipped into an aqueous solution of the active substance containing 4% by volume of acetone. After that, moistened filter paper is placed on the bottom of a plastic cup (volume 200 ml) and dry filter paper is placed on it, as well as shoots of maize and 10 Diabreotlca balteata larvae in the second and third stages of development. All this is maintained at approximately 24 ° C and 40-60% relative humidity and in daylight. The evaluation was carried out after 6 days in relation to untreated control larvae and plants.
Compounds according to the invention 1.15 show an effect of 80-100% (mortality) at a concentration of 400 ppm.
Example 13. Action against the nymph Nephotettix cincticeps.
The test is carried out on grown plants. For this, about 20 days old rice plants are grown to a height of about 15 cm in pots with a diameter of 5.5 cm.
The plants are sprayed on a rotating plate with an acetone solution of 100 ml, respectively, containing 400 ppm of the active substance to be tested. After the applied layer dries, 20 insect nymphs are planted on each plant in the second and third stages of development. To prevent the cicadas from jumping out, plastic cylinders, each of which is covered with a mesh cover, are placed over the test pieces. Nymphs are kept for 5 days on treated plants that are watered at least once. The test was carried out at a temperature of about 23 ° C, at a relative humidity of 55% and a light period of 16 hours.
Compound 1.1 shows an 80-100% effect in this test.
Example 14. Insecticidal effect of feed and against Plutella xylostella.
Chinese cabbage plants grown in pots with a diameter of 10 cm, up to the stage
the appearance of the fourth sheet / sprayed with an aqueous emulsion of the active substance, with a concentration of 3-400 ppm, and allow the applied layer to dry.
After two days, 10 Platella xylostella larvae in the second stage of development are placed on the treated plants of Chinese cabbage. The test was conducted at 24 ° C and a relative humidity of 60% at dusk. Evaluation was carried out in 2 and 5 days. Larvae mortality is determined.
Effects 80-100% (mortality) show compounds 1.1, 1.2. 1.3, 1.5-1.32 and 1.41-1.43 in this test at a concentration
400 ppm
Example 15 (comparative). The proposed compounds as pesticides are superior to the known 4,6-triamino-5-nitropyrimidines. With biological
Comparison has shown that compound 1.1 according to a compound of formula
25
/ VNH-
NH2
shows in relation to Lucllla serlcata in accordance with the experience of Example 8
100% mortality at 0.004-0.01 ppm and against Lucflia cuprina and in accordance with the experience of the example 9 100% mortality at 0.01-0.03 ppm.
In contrast, with equal
test conditions for the compound of formula
NaK Dt-ShOgN- N NH2
which is an insecticidal compound in accordance with the known, it is necessary to apply for 100% killing of Lucilla sericata 0.16 ppm and Lucllla cuprina 0.41 ppm.
The resulting compounds exhibit higher pesticidal activity as compared with the known structure and use.

权利要求:
Claims (1)
[1]
The invention of the method of obtaining the pyrimidins of the general formula (I)
. R3-NH-A-: NSC-VN RJ
R
where Ri is hydrogen or Ci-Gi-alkyl;
Ra SgCl-alkyl or Cz-Ce-cycloalkyl or Rt and R2 together one of the residues - (CHaM - or
R3 is hydrogen;
R4 --NH2-or-NH-CO-R5J
R5-Cr-C4-afl "m or perhalogenated Ci-Cz-alkyl,
or their acid addition salts, in that the compound of formula (II) I N
H2N - “s-Ci
NH2
subjected to interaction with the compound of General formula (III)
Us:
RI-
and the resulting compound of formula (I), where RA is MY2, if necessary is converted into a compound of formula (I), where R4 is NH-CO-RS, followed by isolation of the compound of formula (I) in free form or in the form of its acidic -additive salt.
1.23
- C2H5
-czns
Table
NW-CO-C4H, (p) 119-120
Table 2

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同族专利:

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公开号 | 公开日

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HU903977D0|1990-11-28|

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PT84774B|1989-12-29|

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AU7219487A|1987-11-05|

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HK11694A|1994-02-18|

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HU204396B|1992-01-28|

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DK217787A|1987-10-31|

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DK61792D0|1992-05-12|

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ES2051771T3|1994-07-01|

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HUT44895A|1988-05-30|

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AR247389A1|1994-12-29|

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DE3781196D1|1992-09-24|

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DD270907A5|1989-08-16|

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NZ220132A|1990-06-26|

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DK165690C|1993-05-24|

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CA1292231C|1991-11-19|

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CS307587A2|1990-02-12|

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GR3005856T3|1993-06-07|

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PH24337A|1990-06-13|

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AT79614T|1992-09-15|

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DK61792A|1992-05-12|

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DK61692A|1992-05-12|

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TR22942A|1988-12-08|

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EP0244360B1|1992-08-19|

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DK61692D0|1992-05-12|

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CN87103168A|1987-12-16|

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PT84774A|1987-05-01|

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HUT44128A|1988-02-29|

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ZA873082B|1987-12-30|

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CS271471B2|1990-10-12|

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BR8702106A|1988-02-09|

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HU201651B|1990-12-28|

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SU1657061A3|1991-06-15|

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JPH0688981B2|1994-11-09|

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AU598254B2|1990-06-21|

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EP0244360A2|1987-11-04|

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US4783468A|1988-11-08|

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JPS62263162A|1987-11-16|

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DK217787D0|1987-04-29|

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DK165690B|1993-01-04|

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HU9203430D0|1993-03-01|

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KR870010011A|1987-11-30|

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引用文献:

---

公开号 | 申请日 | 公开日 | 申请人 | 专利标题

---

---

CH376115A|1957-12-06|1964-03-31|Ciba Geigy|Process for the preparation of new substituted pyrimidines|

---

CH574206A5|1972-11-16|1976-04-15|Ciba Geigy Ag|

---

GB1523274A|1974-08-05|1978-08-31|Ici Ltd|Herbicidal compositions containing substituted pyrimidine|

---

CA1072556A|1976-08-27|1980-02-26|Fmc Corporation|Herbicidal 5-pyrimidinecarbonitriles|

---

US4092150A|1976-08-27|1978-05-30|Fmc Corporation|Herbicidal 5-pyrimidinecarbonitriles|

---

DD157192A1|1981-03-13|1982-10-20|Rainer Evers|PROCESS FOR SYNTHESIS OF 2-FUNCTIONALIZED 4-ALKYLTHIO-6-AMINO-PYRIMIDIN-5-CARBONITRILES|

---

CH652396A5|1981-12-07|1985-11-15|Ciba Geigy Ag|AMINO-5-NITROPYRIMIDINE DERIVATIVES.|

---

DE3205638A1|1982-02-17|1983-08-25|Hoechst Ag, 6230 Frankfurt|Trisubstituted pyrimidine-5-carboxylic acids and their derivatives, processes for their preparation, and their use as pesticides|US2941794A|1956-04-13|1960-06-21|Geddes Edith Bel|Building structures|

---

EP0508353B1|1991-04-11|1996-06-26|Lonza Ag|Process for the preparation of 4-amino-2-chloro-5-cyano-6-pyrimidine|

---

RU95113597A|1992-12-02|1997-06-10|ФМК Корпорейшн |Insecticide composition, method of insect control|

---

US5344955A|1993-02-19|1994-09-06|Ciba-Geigy Corporation|Preparation of 1-amino-cyan-amido-2,2-dicyanoethylene, sodium salt|

---

DE4311901A1|1993-04-10|1994-10-13|Huels Chemische Werke Ag|New azeomethines, a process for their preparation and their use|

---

AU7385994A|1993-07-26|1995-02-20|Ciba-Geigy Ag|Process for the preparation of substituted 4,6-diamino-5-cyanopyrimidines|

---

BR9715292B1|1996-04-29|2013-04-09|pesticide composition, method of pest control as well as use thereof.|

---

CN1157381C|1997-08-27|2004-07-14|诺瓦提斯公司|Dicyclanil polymorphs and hydrates and their preparation|

---

AU2007202548B1|2007-06-01|2007-11-01|Jurox Pty Ltd|Pesticide Composition|

---

WO2009118312A1|2008-03-28|2009-10-01|Novartis Ag|Dicyclanil formulation|

---

AU2010201828A1|2009-05-08|2010-11-25|Jurox Pty Ltd|Veterinary composition|

---

AU2010295338B2|2009-09-21|2014-05-15|Boehringer Ingelheim Animal Health USA Inc.|Dicyclanil-based aqueous suspension and non-aqueous solution pour-on and spray on formulations for the prevention and treatment of insect infestation in animal|

---

CN102113496B|2010-01-03|2013-04-03|海利尔药业集团股份有限公司|Bactericidal composition containing dicyclanil and methomyl|

---

JP5731205B2|2011-01-14|2015-06-10|株式会社エス・ディー・エス バイオテック|Pyrimidine derivatives as pest control agents for agriculture and horticulture|

---

CN102250017A|2011-06-15|2011-11-23|扬州天和药业有限公司|Synthesizing method of dicyclanil|

---

CN102399193A|2011-12-15|2012-04-04|连云港市亚晖医药化工有限公司|Method for preparing 4,6-diamino-2--5-pyrimidinecarbonitrile|

---

CN103416420B|2012-05-18|2015-10-14|陕西汤普森生物科技有限公司|A kind of Pesticidal combination containing CGA 183893|

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CN103416430B|2012-05-24|2016-01-13|陕西汤普森生物科技有限公司|A kind of composition pesticide|

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CN103444765A|2012-05-31|2013-12-18|陕西汤普森生物科技有限公司|Dicyclanil and pyrethroid-containing insecticidal composition|

---

JP2015003900A|2013-05-23|2015-01-08|宮崎みどり製薬株式会社|Dermanyssus gallinae control agent|

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---

CN104130197A|2014-07-29|2014-11-05|华中农业大学|Chemical synthetic method of 2,4,6-triamido-5-cyano pyrimidine|

---

CN104649982B|2015-02-26|2016-12-07|齐鲁晟华制药有限公司|A kind of preparation method of Dicyclanil|

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PL239600B1|2018-09-20|2021-12-20|Icb Pharma Tomasz Swietoslawski Pawel Swietoslawski Spolka Jawna|New dicyclanil salt, method for obtaining such salt, compositions containing such salt, and use of such salt to combat and control parasites, and in particular fly larvae|

法律状态:

优先权:

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申请号 | 申请日 | 专利标题

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CH177286|1986-04-30|

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