US 2021/0276958 A1 · METHOD FOR PRODUCING SUBSTITUTED N-ARYL PYRAZOLES

Abstract

The present invention relates to a process for preparing compounds of the formula (I) starting from compounds of the formula (II) in which R1, R2 and R3 have the abovementioned meaning and where R1 and R3 are not simultaneously hydrogen in any compound. The invention further provides the compounds of the formulae (IVa), (IVb), (V) and (VI) in which R1, R2, R3, R5, M and n have the abovementioned meaning.

Claims22

Dependent claims

A process for preparing a compound of formula (I)
wherein
R1 is hydrogen, cyano, halogen, C1-C4-alkyl optionally substituted by halogen or CN, or C1-C4-alkoxy optionally substituted by halogen,
R2 is trifluoromethylsulfonyl, trifluoromethylsulfinyl, trifluoromethylsulfanyl, halogen, C1-C4-alkyl optionally substituted by halogen, or C1-C4-alkoxy optionally substituted by halogen, and
R3 is hydrogen, cyano, halogen, C1-C4-alkyl optionally substituted by halogen or CN, or C1-C4-alkoxy optionally substituted by halogen,
where R1 and R3 are not simultaneously hydrogen in any compound,
starting from a compound of formula (II) wherein R1, R2 and R3 are as defined for formula (I) and wherein R1 and R3 are not simultaneously hydrogen in any compound,
comprising the following steps (1) to (3)
(1) diazotization with of the compound of formula (II) with a compound of formula RNO2 or M(NO2)n, wherein R is (C1-C6)-alkyl, n is one or two and M is ammonium, an alkali metal (with n=1) or an alkaline earth metal (with n=2), and at least one acid selected from mineral acids, sulfonic acids or carboxylic acids, wherein the carboxylic acids have a pKa of ≤2,
(2) reduction with ascorbic acid;
and
(3) cyclization with a 1,1,3,3-tetra(C1-C4)alkoxypropane in a polar solvent in the presence of at least one acid selected from mineral acids, sulfonic acids or carboxylic acids, where the carboxylic acids have a pKa ≤2.

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18:

The process according to claim 17, wherein the conversion of a compound of the formula (II) over steps (1), (2) and (3), and optionally (2-b), into a compound of the formula (I) meets at least one of the following conditions:
i) there is no isolation of the diazonium salt (III) from the reaction mixture of step (1);
ii) there is no purification of the diazonium salt (III) from the reaction mixture of step (1);
iii) there is no isolation of compounds of the formula (IVa), (IVb), (VI) or of any compounds of the formula (VIII) formed from the reaction mixture of step (2) or (2-b);
iv) there is no purification of compounds of the formula (IVa), (IVb), (VI) or of any compounds of the formula (VIII) formed from the reaction mixture of step (2) or (2-b);
v) all steps (1), (2) and (3) and optionally (2-b) take place in the same reaction vessel;
vi) from the solvent of step (1) only a small proportion of the solvent is removed prior to the start of step (2) or prior to the start of step (2-b) or (3), preferably less than 50% by volume (percent by volume based on the volume of solvent used), preferably less than 30% by volume, more preferably less than 10% by volume, even more preferably at most 5% by volume of the solvent (e.g. by evaporation, for example at a reaction temperature of about 40° C., or active removal, e.g. by distillation and/or reduced pressure based on 1013 hPa), preferably no solvent is actively removed by the solvent exchange between step (1) and step (2), between step (2), any step (2-b), and (3) and, if present, between step (2) and (2-b) (e.g. by distillation and/or reduced pressure based on 1013 hPa);
vii) there is only a small exchange, preferably no exchange, of solvent between step (1) and (2) and between step (2) and (3) and, if present, between step (2) and (2-b) and between step (2-b) and (3), particularly preferably at most 50% by volume, preferably at most 40% by volume, more preferably at most 30% by volume, even more preferably at most 20% by volume, of the solvent used in step 1 is replaced by a new solvent (the new solvent can be the same solvent or another solvent).

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Facts

Application

17/058,035Filed 20 May 2019

Priority

EP 18174045.724 May 2018

Published

9 Sep 2021

Term ends

Not estimatedThe source records don’t support an estimate.

Classification5 codes

C07D 231/12
Having two or three double bonds between ring members or between ring members and non-ring members: with only hydrogen atoms, hydrocarbon or…
C07C 243/28
With acylating carboxyl groups bound to hydrogen atoms or to acyclic carbon atoms: to hydrogen atoms or to carbon atoms of a saturated carbon skeleton
C07D 307/20
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,…:…
C07D
Heterocyclic compounds

Abstract

Claims22

Dependent claims

A process for preparing a compound of formula (I)
wherein
R1 is hydrogen, cyano, halogen, C1-C4-alkyl optionally substituted by halogen or CN, or C1-C4-alkoxy optionally substituted by halogen,
R2 is trifluoromethylsulfonyl, trifluoromethylsulfinyl, trifluoromethylsulfanyl, halogen, C1-C4-alkyl optionally substituted by halogen, or C1-C4-alkoxy optionally substituted by halogen, and
R3 is hydrogen, cyano, halogen, C1-C4-alkyl optionally substituted by halogen or CN, or C1-C4-alkoxy optionally substituted by halogen,
where R1 and R3 are not simultaneously hydrogen in any compound,
starting from a compound of formula (II) wherein R1, R2 and R3 are as defined for formula (I) and wherein R1 and R3 are not simultaneously hydrogen in any compound,
comprising the following steps (1) to (3)
(1) diazotization with of the compound of formula (II) with a compound of formula RNO2 or M(NO2)n, wherein R is (C1-C6)-alkyl, n is one or two and M is ammonium, an alkali metal (with n=1) or an alkaline earth metal (with n=2), and at least one acid selected from mineral acids, sulfonic acids or carboxylic acids, wherein the carboxylic acids have a pKa of ≤2,
(2) reduction with ascorbic acid;
and
(3) cyclization with a 1,1,3,3-tetra(C1-C4)alkoxypropane in a polar solvent in the presence of at least one acid selected from mineral acids, sulfonic acids or carboxylic acids, where the carboxylic acids have a pKa ≤2.

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18:

The process according to claim 17, wherein the conversion of a compound of the formula (II) over steps (1), (2) and (3), and optionally (2-b), into a compound of the formula (I) meets at least one of the following conditions:
i) there is no isolation of the diazonium salt (III) from the reaction mixture of step (1);
ii) there is no purification of the diazonium salt (III) from the reaction mixture of step (1);
iii) there is no isolation of compounds of the formula (IVa), (IVb), (VI) or of any compounds of the formula (VIII) formed from the reaction mixture of step (2) or (2-b);
iv) there is no purification of compounds of the formula (IVa), (IVb), (VI) or of any compounds of the formula (VIII) formed from the reaction mixture of step (2) or (2-b);
v) all steps (1), (2) and (3) and optionally (2-b) take place in the same reaction vessel;
vi) from the solvent of step (1) only a small proportion of the solvent is removed prior to the start of step (2) or prior to the start of step (2-b) or (3), preferably less than 50% by volume (percent by volume based on the volume of solvent used), preferably less than 30% by volume, more preferably less than 10% by volume, even more preferably at most 5% by volume of the solvent (e.g. by evaporation, for example at a reaction temperature of about 40° C., or active removal, e.g. by distillation and/or reduced pressure based on 1013 hPa), preferably no solvent is actively removed by the solvent exchange between step (1) and step (2), between step (2), any step (2-b), and (3) and, if present, between step (2) and (2-b) (e.g. by distillation and/or reduced pressure based on 1013 hPa);
vii) there is only a small exchange, preferably no exchange, of solvent between step (1) and (2) and between step (2) and (3) and, if present, between step (2) and (2-b) and between step (2-b) and (3), particularly preferably at most 50% by volume, preferably at most 40% by volume, more preferably at most 30% by volume, even more preferably at most 20% by volume, of the solvent used in step 1 is replaced by a new solvent (the new solvent can be the same solvent or another solvent).

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Method for producing substituted n-aryl pyrazoles

Life of this patent

Abstract

Claims22

Method for producing substituted n-aryl pyrazoles

Life of this patent

Abstract

Claims22