Process for the preparation of substituted pyridine compounds and intermediates thereof

A continuous or semicontinuous flow process for the preparation of a compound of formula (I) or a salt thereof,

• wherein,
• R1 is selected from the group of halogens and C1-C4 alkoxy;
• R2 is selected from the group consisting of hydrogen, halogen, C1-C4 alkyl, C3-C7 cycloalkyl, C1-C3 haloalkyl, heterocyclyl, O—R′, haloalkyl and O—C(O)R′;
• R3 is selected from the group consisting of hydrogen, halogen C1-C4 alkyl, C3-C7 cycloalkyl, C1-C3 haloalkyl and C1-C4 alkoxy;
• R4 is selected from the group consisting of hydrogen, halogen, C1-C4 alkyl, C3-C7 cycloalkyl, C1-C3 haloalkyl, heterocyclyl, O—R′, haloalkyl, O—C(O)R′ and CHO;
• R′ is selected from the group consisting of C1-C6-alkyl and C1-C3 haloalkyl;
• wherein R3 and R4 can form a 5-6 membered ring system, which is optionally substituted by halogen, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy;
• R3 and R4 groups are optionally substituted with halogen, CN, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy;
• comprising the steps of:
• A. cyclizing a vinylogous nitrile of formula (II) or a salt thereof,
• by reacting with a suitable acid (reagent-1) and optionally in the presence of a solvent;
• according to the reaction scheme-1 as depicted below:
• wherein LG represents OR′ or N(R′)2;
• R′, R1, R2, R3 and R4 are as defined above;
• B. by reacting an α,β-unsaturated nitrile of formula (III) or a salt thereof, with reagent-2 selected from:
• i. with a compound of formula (R5)2NCHO or a salt thereof and co-reagent (C-1)
• or
• ii. with a suitable amine compound of formula NH(R5)2 or a salt thereof, suitable ortho esters compound of formula CR7(OR5)3 or a salt thereof and co-reagent (C-2),
• and optionally in the presence of a suitable solvent, according to the reaction scheme-2 as depicted below:
• wherein, LG, co-reagents, R1, R2, R3, R4, R5, R6 and R7are as defined above.

A continuous or semicontinuous flow process for the preparation of a compound of formula (I) or salt thereof,

• wherein,
• R1 and R2 represents halogen;
• R3 is selected from the group consisting of hydrogen, halogen C1-C4 alkyl, C3-C7 cycloalkyl, C1-C3 haloalkyl and C1-C4 alkoxy;
• R4 is selected from the group consisting of hydrogen, halogen, C1-C4 alkyl, C3-C7 cycloalkyl, C1-C3 haloalkyl, heterocyclyl, O—R′, haloalkyl, O—C(O)R′ and CHO;
• R′ is selected from the group consisting of C1-C6-alkyl and C1-C3 haloalkyl;
• wherein R3 and R4 can form a 5-6 membered ring system, which is optionally substituted by halogen, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy;
• R3 and R4 groups are optionally substituted with halogen, CN, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy:
• comprising the steps of:
• A. cyclizing a vinylogous nitrile of formula (II) or a salt thereof, by reacting with a suitable acid (reagent-1) and optionally in the presence of a solvent, according to the reaction scheme-1 as depicted below:
• wherein LG represents OR′ or N(R′)2;
• R′ represents C1-C6-alkyl;
• R1, R2, R3 and R4 are as defined above;
• B. by reacting an α,β-unsaturated nitrile of formula (III) or a salt thereof,
• i. with a compound of formula (R5)2NCHO or a salt thereof and co-reagent (C-1)
• or
• ii. with a suitable amine compound of formula NH(R5)2 or a salt thereof, suitable ortho esters compound of formula CR7(OR5)3 or a salt thereof and co-reagent (C-2),
• and optionally in the presence of a suitable solvent, according to the reaction scheme-2 as depicted below:
• wherein, LG, co-reagents, R1, R2, R3, R4, R5, R6 and R7are as defined above;
• C. obtaining the α,β-unsaturated nitrile of formula (III) or a salt thereof,
• from a substituted acrylonitrile compounds of formula (III-b) or a salt thereof,
• by halogenation, in the presence of a halogenating reagent and optionally in the presence of a reagent-3 and a suitable solvent, according to the reaction scheme-3a as depicted below:
• wherein R2 is halogen;
• R3 and R4 are as defined above.