WO2022259210A1 - Nouveau procédé de préparation de 1-méthyl-3-(trifluorométhyl)-1h-pyrazol-5-ol - Google Patents

Nouveau procédé de préparation de 1-méthyl-3-(trifluorométhyl)-1h-pyrazol-5-ol Download PDF

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Publication number
WO2022259210A1
WO2022259210A1 PCT/IB2022/055396 IB2022055396W WO2022259210A1 WO 2022259210 A1 WO2022259210 A1 WO 2022259210A1 IB 2022055396 W IB2022055396 W IB 2022055396W WO 2022259210 A1 WO2022259210 A1 WO 2022259210A1
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WO
WIPO (PCT)
Prior art keywords
methyl
formula
methyl hydrazine
pyrazol
trifluoromethyl
Prior art date
Application number
PCT/IB2022/055396
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English (en)
Inventor
Javed Iqbal
Aman IQBAL
Prasad Narasimhulu CHANDALA
Patrick Perlmutter
Original Assignee
Incor Renovis Pharma Private Limited
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Filing date
Publication date
Application filed by Incor Renovis Pharma Private Limited filed Critical Incor Renovis Pharma Private Limited
Publication of WO2022259210A1 publication Critical patent/WO2022259210A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D231/18—One oxygen or sulfur atom
    • C07D231/20—One oxygen atom attached in position 3 or 5

Definitions

  • the present invention relates to a method for preparation of a pyrazole compound, particularly, a compound having formula used as an intermediate in the manufacturing of pharmaceutical and agricultural chemicals, such as pyroxasulfone.
  • Pyrazole compound having formula I, (I), commonly known as 1-Methyl-3-(Trifluoromethyl)-1 H- Pyrazol-5-ol is a useful research chemical and key intermediate for important building blocks in pharmaceuticals and agrochemicals.
  • Prior art document CN Pat. No. 101824000 teaches a method for synthesis of 1-methyl-3-trifluoromethyl pyrazol by reacting trifluoroacetyl vinyl alkyl ether with methyl hydrazine.
  • Another prior art document WO2017084995 teaches synthesis of 1-Methyl-3-(Trifluoromethyl)-1 H-pyrazol-5-ol from ethyl 4,4,4- trifluoroacetoacetate and methyl hydrazine.
  • Still another prior art document WO201 8154097 teaches a method for synthesis of 1 -methyl-3- (trifluoromethyl)-1 H-pyrazol-5-ol by reacting ethyl 4,4,4-trifluoroacetoacetate with methyl hydrazine in the presence of 1-methyl-3-(trifluoromethyl)-1 H- pyrazol-5-ol.
  • methyl hydrazine is one of the key raw materials in the synthesis of 1-Methyl-3-(Trifluoromethyl)-1 H-Pyrazol-5-ol.
  • Methyl hydrazine is a volatile liquid and a potent carcinogen.
  • the chemical has a high acute oral, dermal and inhalation toxicity. Some studies have also reported evidence of DNA damage and reproductive or developmental toxicity from the chemical. Further, handling of methyl hydrazine requires adherence to stringent health and safety legislation and control measures to minimize risk. Owning to the health and safety risks and stringent handling guidelines, methyl hydrazine is costly and has limited accessibility.
  • the present invention aims to overcome the drawbacks of the prior art by a novel method for synthesis of 1-Methyl-3-(Trifluoromethyl)-1 H-Pyrazol-5-ol which alleviates the human health and environmental impacts of the previously known methods.
  • an object of the present invention is to provide a novel process for the preparation of 1-Methyl-3-(Trifluoromethyl)-1H-Pyrazol-5-ol which eliminates the use of methyl hydrazine as a key raw material.
  • Another object of the present invention is to provide a single-step process for the preparation of 1-Methyl-3-(Trifluoromethyl)-1 H-Pyrazol-5-ol which is simple, safe, economical and environmental-friendly.
  • a process for preparation of a pyrazole compound having formula (I) comprising the steps of: condensing a compound having formula (II) (II) with a methyl hydrazine salt in an acidic medium, where R is selected from C 1 -5 alkyl, aryl and C 3-7 cycloalkyl.
  • the pyrazole compound of formula (I) is 1-Methyl-3- (Trifluoromethyl)-1 H-Pyrazol-5-ol.
  • the compound of formula (II) is preferably alkyl 4,4,4-trifluoroacetoacetate, and more preferably, ethyl 4,4,4- trifluoroacetoacetate.
  • the methyl hydrazine salt is selected from methyl hydrazine hydrochloride, methyl hydrazine sulfate, methyl hydrazine oxalate, and the like.
  • the acidic medium consists of an acid in a solvent.
  • the acid is selected from hydrochloric acid, sulfuric acid, trifluoroacetic acid, acetic acid, and the like.
  • the solvent is selected from water, ethanol, methanol, diethyl ether, and the like.
  • the process is carried out at a reaction temperature between 25 to 100 °C.
  • the reaction is carried out in the presence of a buffering agent selected from sodium acetate, potassium acetate, and the like.
  • the present invention relates to a process for synthesis of a pyrazole compound having formula (I), (I).
  • the process includes condensing a compound having formula (II), (II), with a methyl hydrazine salt in an acidic medium.
  • R is selected from C 1 -5 alkyl, aryl and C 3-7 cycloalkyl.
  • alkyl refers to a straight or branched chain aliphatic hydrocarbon chain, having from 1 to 5 carbon atoms. Examples of alkyl include, but are not limited to methyl, ethyl, n-propyl, isopropyl, n-butyl, n-pentyl, t-butyl, and the like.
  • cycloalkyl refers to cyclic alkyl groups constituting of 3 to 7 carbon atoms having a single cyclic ring or multiple condensed rings, such cycloalkyl groups include, by way of example, single ring structures, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and the like, or multiple ring structures.
  • aryl refers to a mono- or poly- carbocyclic aromatic group, for example phenyl or naphthyl ring and the like.
  • the pyrazole compound of formula (I) is preferably 1-Methyl-3- (Trifluoromethyl)-1 H-Pyrazol-5-ol.
  • the compound having formula (II) is an alkyl 4,4,4-trifluoroacetoacetate, preferably, ethyl 4,4,4-trifluoroacetoacetate.
  • the methyl hydrazine salt is selected from methyl hydrazine hydrochloride, methyl hydrazine sulfate, methyl hydrazine oxalate, and the like. Hydrazine salts are neutralized compounds having better stability as compared to methyl hydrazine. The salts of methyl hydrazine are more economical, safer in terms of oral, dermal and inhalation toxicity, and easy-to-access in terms of handling, storage and availability.
  • the ratio of the alkyl 4,4,4-trifluoroacetoacetate and methyl hydrazine salt is in the range of 1 :1 to 1 :1.5, preferably 1 :1.
  • the reaction is carried out at a temperature between 25 to 100 °C in an acidic medium.
  • the acidic medium consists of an acid in a solvent.
  • the acid is selected from hydrochloric acid, sulfuric acid, trifluoroacetic acid, acetic acid, and the like.
  • the solvent is selected from water, ethanol, methanol, diethyl ether, and the like.
  • the ratio of the acid and the solvent is in the range of 0 : 3 to 1 : 1 , preferably 0 : 3.
  • a buffering agent may be selectively added to the alkyl 4,4,4- trifluoroacetoacetate to adjust its pH in the range of 2.5 to 8. Alternatively, the reaction may be carried out without any buffering agent.
  • the buffering agent is selected from sodium acetate, potassium acetate, and the like.
  • the buffering agent is added to the alkyl 4,4,4-trifluoroacetoacetate, and then the alkyl 4,4,4- trifluoroacetoacetate is reacted with the methyl hydrazine salt to obtain 1- Methyl-3-(Trifluoromethyl)-1 H-Pyrazol-5-ol.
  • the ratio of the alkyl 4,4,4- trifluoroacetoacetate and the buffering agent is in the range of 1 : 1 to 1 : 3, preferably 1 : 2.
  • the compound of Formula I is obtained by condensation of ethyl 4,4,4-trifluoroacetoacetate with methyl hydrazine sulfate in aqueous sulfuric acid at reaction temperature between 25 to 100 °C.
  • the reaction scheme is illustrated here below in
  • the compound of Formula I is obtained by condensation of ethyl 4,4,4-trifluoroacetoacetate with methyl hydrazine hydrochloride in aqueous acetic acid in the presence of sodium acetate.
  • the compound of Formula I is obtained by condensation of ethyl 4,4,4-trifluoroacetoacetate with methyl hydrazine oxalate in a medium of ethanol and trifluoroacetic acid in the presence of potassium acetate.
  • the compound of Formula I is obtained by condensation of ethyl 4,4,4-trifluoroacetoacetate with methyl hydrazine sulfate in a medium of methanol and hydrochloric acid.
  • Example 1 Preparation of 1-Methyl-3-(Trifluoromethyl)-1 H-Pyrazol-5-ol Ethyl-4, 4, 4-trifloroacetoacetate (1 g, 5.4 mmol) was treated with methylhydrazine sulfate (0.782 g, 5.4 mmol) in acetic acid (2.5 ml) and water (3 ml) at 85°C for 24 h. Reaction mixture was extracted with ethyl acetate (2 x 20 ml). Combined organic layers were washed with water (20 ml) and brine solution (20 ml) successively. Volatiles were evaporated to obtain residue that was washed with hexane (10 ml) to obtain 1-Methyl-3-(Trifluoromethyl)-1 H- Pyrazol-5-ol as white solid (340 mg).
  • Embodiment of the present invention is applicable over a wide number of uses and other embodiments may be developed beyond the embodiment discussed heretofore. Only the most preferred embodiments and their uses have been described herein for purpose of example, illustrating the advantages over the prior art obtained through the present invention; the invention is not limited to these specific embodiments or their specified uses. Thus, the forms of the invention described herein are to be taken as illustrative only and other embodiments may be selected without departing from the scope of the present invention. It should also be understood that additional changes and modifications, within the scope of the invention, will be apparent to one skilled in the art and that various modifications to the composition described herein may fall within the scope of the invention.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

L'invention concerne un procédé de préparation de 1-méthyl-3-(trifluorométhyl)-1h-pyrazol-5-ol. Le procédé comprend la condensation d'un composé de formule (II) avec un sel d'hydrazine de méthyle dans un milieu acide. Le composé de formule (II) est un alkyl 4,4,4-trifluoroacétoacétate. Le procédé est simple, sûr, économique et respectueux de l'environnement, et élimine l'utilisation d'hydrazine de méthyle en tant que matière première clé.
PCT/IB2022/055396 2021-06-10 2022-06-10 Nouveau procédé de préparation de 1-méthyl-3-(trifluorométhyl)-1h-pyrazol-5-ol WO2022259210A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN202141025874 2021-06-10
IN202141025874 2021-06-10

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WO2022259210A1 true WO2022259210A1 (fr) 2022-12-15

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017084995A1 (fr) * 2015-11-16 2017-05-26 Lonza Ltd Procédé de préparation de 1-méthyl-3-(trifluorométhyle)-1h-pyrazol-5-ol
CN111187215A (zh) * 2020-01-21 2020-05-22 西北农林科技大学 含氟吡唑酰胺类衍生物、制备方法及其应用

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017084995A1 (fr) * 2015-11-16 2017-05-26 Lonza Ltd Procédé de préparation de 1-méthyl-3-(trifluorométhyle)-1h-pyrazol-5-ol
CN111187215A (zh) * 2020-01-21 2020-05-22 西北农林科技大学 含氟吡唑酰胺类衍生物、制备方法及其应用

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