WO2021134943A1 - Forme cristalline de flazasulfuron et son procédé de préparation - Google Patents

Forme cristalline de flazasulfuron et son procédé de préparation Download PDF

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Publication number
WO2021134943A1
WO2021134943A1 PCT/CN2020/082259 CN2020082259W WO2021134943A1 WO 2021134943 A1 WO2021134943 A1 WO 2021134943A1 CN 2020082259 W CN2020082259 W CN 2020082259W WO 2021134943 A1 WO2021134943 A1 WO 2021134943A1
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Prior art keywords
flazasulfuron
crystal form
present
solvent
preparation
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PCT/CN2020/082259
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English (en)
Chinese (zh)
Inventor
戴耀
王荣良
梁全德
刘玲玲
张小红
赵鑫
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大连九信精细化工有限公司
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Publication of WO2021134943A1 publication Critical patent/WO2021134943A1/fr

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    • C—CHEMISTRY; METALLURGY
    • 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
    • C07D401/12—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 linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

Definitions

  • the invention belongs to the technical field of compound crystals, and specifically relates to a flazasulfuron crystal form and a preparation method thereof.
  • Flazasulfuron (English generic name Flazasulfuron) is a broad-spectrum sulfonylurea herbicide developed by Ishihara Sangyo Kaisha in Japan in the 1980s (see CN85109761). Flusulfuron-methyl is very effective in selectively suppressing weeds on open ground. It can be weeded by root or leaf absorption, and it can even be sprayed directly in the soil to prevent weeds. It can be used in a variety of ways. The growth of weeds stopped within a few hours after the application of flazasulfuron. Symptoms include leaf discoloration, dryness, necrosis, and eventually death within 20 to 25 days after application.
  • Flusulfuron-methyl has a wide range of activities and can inhibit annual and perennial weeds, especially many broad-leaved weeds.
  • the existing flazasulfuron has relatively high impurity content, is not easy to separate, and the stability, efficacy and preparation processability all need to be improved.
  • the present invention researches and designs a crystal form of flazasulfuron and a preparation method thereof to improve the shortcomings of insufficient purity of traditional amorphous flazasulfuron and insufficient stability.
  • the technical means adopted in the present invention are as follows:
  • it has an X-ray powder diffraction pattern as shown in FIG. 1.
  • the differential scanning calorimetry curve of the crystal form has an endothermic peak at 177-181°C, and an exothermic peak at 181-190°C and 239-282°C.
  • a preparation method of flazasulfuron crystal form comprising the following steps:
  • S3 The solid-liquid mixture obtained by S2 is subjected to solid-liquid separation to obtain flazasulfuron crystals.
  • step S1 the mixture of flazasulfuron and the solvent is heated to reflux, and the heating is stopped after dissolving, and the solvent is acetonitrile; in step S2, the speed of cooling and crystallization is 5°C/10 minutes; In S3, the method of solid-liquid separation is suction filtration and drying.
  • the flazasulfuron used is flazasulfuron with a purity of 90%.
  • the flazasulfuron crystal form prepared by the present invention uses the same low content of flazasulfuron raw materials, and the product can be better separated from impurities. After forming a crystalline state, the product purity and recovery rate are higher. , It is easier to obtain high-purity APIs. In addition, the thermal stability is good, which is more conducive to the requirements of production, transportation and storage. It has a longer shelf life, better slow-release performance, increased drug efficacy, better formulation processability, improved processing efficiency, and stable production technology, adaptable For industrial production.
  • Figure 1 is an X-ray powder diffraction pattern of the crystal form of flazasulfuron in Example 1 of the present invention
  • Example 2 is a DSC/TGA chart of the crystal form of flazasulfuron in Example 1 of the present invention
  • Figure 3 is an infrared spectrum of the crystal form of flazasulfuron in Example 1 of the present invention.
  • Figure 4 is an X-ray powder diffraction pattern of amorphous flazasulfuron in the comparative example of the present invention.
  • Figure 5 is the DSC/TGA spectrum of amorphous flazasulfuron in the comparative example of the present invention.
  • the testing instrument and method used in the present invention is a measuring instrument and method used in the present invention.
  • the present invention uses low-content amorphous flazasulfuron as a raw material and uses organic solvents to recrystallize to obtain crystalline flazasulfuron.
  • the structure has the following formula.
  • the crystal form has the advantages of high purity and good stability.
  • organic solvent used for recrystallization is one or a mixture of acetonitrile and propionitrile.
  • the crystalline form of flazasulfuron described in the present invention uses Cu-K ⁇ radiation to obtain an X-ray powder diffraction pattern expressed in 2 ⁇ angles.
  • the crystal includes the 2 ⁇ values of 4.6°, 6.9°, 8.3°, 9.2 °, 11.5°, 13.4°, 13.8°, 14.7°, 15.2°, 15.4°, 16.7°, 17.4°, 17.8°, 18.4°, 19.6°, 20.6°, 21.4°, 21.8°, 22.9°, 23.4°, 24.1°, 24.5°, 25.1°, 25.9°, 26.4°, 27.1°, 27.9°, 28.1°, 28.5°, 29.6°, 29.9°, 30.7°, 31.3°, 32.5°, 33.3°, 33.9°, 34.5° , 34.9°, 35.7°, 36.2°, 36.8°, 37.3° and 38.2°.
  • the error range of the above-mentioned 2 ⁇ angle values is ⁇ 0.2°.
  • the above crystal form of flazasulfuron has an X-ray powder diffraction pattern as shown in Fig. 1; the differential scanning calorimetry curve of this crystal form has an endothermic peak at 177-181°C, and at 181-190°C And there is an exothermic peak at 239-282°C; the infrared absorption spectrum of this crystal form is at 3093cm -1 , 2945cm -1 , 1737cm -1 , 1622cm -1 , 1578cm -1 , 1512cm -1 , 1495cm -1 , 1452cm -1 , 1417cm -1, 1362cm -1, 1268cm -1, 1233cm -1, 1199cm -1, 1169cm -1, 1156cm -1, 1127cm -1, 1037cm -1, 1012cm -1, 987cm -1, 916cm -1, 894cm -1, 827c
  • the method for preparing the above-mentioned flazasulfuron crystal form includes the following steps: S1: mixing flazasulfuron with a solvent, heating to 70-100°C, and stopping heating after dissolving, the solvent is acetonitrile and propionitrile Or a mixture of acetonitrile and propionitrile; S2: cooling and crystallization at a speed of 5-10°C/10 minutes, and then keeping it at room temperature and stirring for more than 0.5h; S3: separating the solid-liquid mixture obtained by S2 to obtain pyridine Suimesulfuron crystals.
  • step S1 the mixture of flazasulfuron and the solvent is preferably heated to reflux, and the heating is stopped after dissolving.
  • the solvent is acetonitrile; in step S2, the preferred rate of cooling and crystallization is 5°C/10 minutes;
  • the method of solid-liquid separation is suction filtration and drying.
  • the melting point and decomposition point data of the DSC test show that the melting point and decomposition point of the flazasulfuron crystal form prepared by the present invention are significantly higher than the flazasulfuron in the amorphous state, and its stability is significantly better than that of the amorphous sample.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention se rapporte au domaine technique des cristaux de composés et concerne une forme cristalline de flazasulfuron et son procédé de préparation. Le motif de diffraction de rayons X sur poudre, formé à l'aide d'un rayonnement Cu-Kα, de la forme cristalline est représenté sur la figure 1. Selon la présente invention, lors de l'utilisation d'une même matière première de flazasulfuron à faible teneur, le produit peut être mieux séparé des impuretés, après formation d'un état cristallin, la pureté du produit et le taux de récupération sont plus élevés, et il est plus facile d'obtenir un ingrédient pharmaceutique actif de pureté élevée. De plus, la présente invention a une bonne stabilité thermique, une durée de conservation plus longue, une meilleure performance de libération prolongée, une meilleure aptitude au traitement de préparation, et un procédé de production stable, plus conforme aux exigences de production, de transport et de stockage, permettant d'augmenter l'efficacité de médicament, d'améliorer l'efficacité de traitement, et est approprié pour une production à l'échelle industrielle.
PCT/CN2020/082259 2019-12-30 2020-03-31 Forme cristalline de flazasulfuron et son procédé de préparation WO2021134943A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201911400382.6 2019-12-30
CN201911400382.6A CN111004217A (zh) 2019-12-30 2019-12-30 一种啶嘧磺隆晶型及其制备方法

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WO2021134943A1 true WO2021134943A1 (fr) 2021-07-08

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN85109761A (zh) * 1984-12-06 1986-12-17 石原产业株式会社 N-[(4，6-二甲氧基嘧啶-2-基)氨基羰基]-3-三氟甲基吡啶-2-磺胺及其盐的生产方法，以及含有它的农药组合物
CN102007119A (zh) * 2008-04-18 2011-04-06 石原产业株式会社 嘧啶系化合物的制造方法
CN102111995A (zh) * 2008-05-28 2011-06-29 加特微胶囊股份公司 磺酰脲及其与氟草烟或其它农用化学品的组合在油中的混悬剂浓缩物

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN85109761A (zh) * 1984-12-06 1986-12-17 石原产业株式会社 N-[(4，6-二甲氧基嘧啶-2-基)氨基羰基]-3-三氟甲基吡啶-2-磺胺及其盐的生产方法，以及含有它的农药组合物
CN102007119A (zh) * 2008-04-18 2011-04-06 石原产业株式会社 嘧啶系化合物的制造方法
CN102111995A (zh) * 2008-05-28 2011-06-29 加特微胶囊股份公司 磺酰脲及其与氟草烟或其它农用化学品的组合在油中的混悬剂浓缩物

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
GU BAOQUAN, CHEN YINGHUI, FAN WENZHENG: "Study on the Synthesis of Flazasulfuron", SHANGHAI CHEMICAL INDUSTRY, vol. 33, no. 4, 15 April 2008 (2008-04-15), pages 4 - 7, XP055826894, ISSN: 1004-017X, DOI: 10.16759/j.cnki.issn.1004-017x.2008.04.010 *

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