Process for the manufacture of pyrazoles or pyrimidones

A process for manufacture of a fluorinated or non-fluorinated 5-membered heterocyclic compound containing two nitrogen atoms in the ring system of the said compound;

• wherein the compound is a fluorinated or non-fluorinated pyrazole compound of formula (1)
• wherein
• R1 represents alkyl, haloalkyl, perfluoralkyl;
• R2 represents CO2-alkyl, CO2-haloalkyl, CO2H;
• R3 represents H, halogen, alkyl, haloalkyl, hydroxyl (—OH), wherein the hydroxyl (—OH) is subject to keto-enol tautomerism and the hydroxyl
• (—OH) together with the carbon atom to which it is bound and with the adjacent carbon atom constitute an enol-form (C═CH—OH) which equilibrates with the keto-form (CH—C═O) or partially or completely converts to the enol-form (C═CH—OH) to the keto-form (CH—C═O);
• R4 represents H, alkyl;
• and wherein in each of R1 to R3, independently the term “alkyl” denotes C1-C4-alkyl residue, and independently the term “halo” represents a halogen atom selected from the group consisting of F and Cl;
• wherein the process is comprising the steps of:
• (a) providing an amine compound of formula (I), R4-NH—X, and/or a monohydrate thereof, wherein
• R4 denotes H or a branched or non-branched C1-C4 alkyl group, and
• X denotes a NH2 group,
• (b) providing a carbonyl group containing three ring-carbon-atom precursor compound for the fluorinated or non-fluorinated pyrazole compound of formula (1),
• (c) feeding the amine compound of (a) and the precursor compound of (b), separately or as a mixture, into at least one continuous flow reactor with upper lateral dimensions of about ≤5 mm, and therein
• (d) reacting the said amine compound of (a) with the said precursor compound of (b), under cyclisation to obtain a reaction mixture comprising the fluorinated or non-fluorinated pyrazole compound of formula (1), and
• (e) withdrawing the reaction mixture obtained in (d) from the said continuous flow reactor to yield the fluorinated or non-fluorinated pyrazole compound of formula (1), and
• (f) purifying and/or isolating the fluorinated or non-fluorinated pyrazole compound of formula (1) obtained in (e) to yield a purified and/or isolated fluorinated or non-fluorinated pyrazole compound of formula (1).