METHOD OF PRODUCING ATR KINASE INHIBITORS (EMBODIMENTS) Russian patent published in 2020 - IPC C07D487/04 

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing a compound of formula I-1, comprising steps of: a) reacting a compound of formula 6a* with a compound of formula 27 under suitable conditions for formation of an amide bond, where the corresponding amide bond formation conditions involve reacting a compound of formula 6a* with a compound of formula 27 in an aprotic solvent while heating to form a compound of formula 28; b) purifying compound of formula 28 using corresponding chelating agent for palladium selected from propane-1,2-diamine; ethane-1,2-diamine; ethane-1,2-diamine; propane-1,3-diamine; tetramethylethylenediamine; ethylene glycol; 1,3-bis(diphenylphosphanyl)propane; 1,4-bis(diphenylphosphanyl)butane and 1,2-bis(diphenylphosphanyl)ethane / Pr-1,2-diamine; c) reacting a compound of formula 28 under suitable deprotection conditions, where the corresponding deprotection conditions involve reacting a compound of formula 28 with an acid in the presence of a solvent to form a compound of formula 30; d) reacting a compound of formula 30 with a compound of formula 25 under suitable conditions for formation of an amide bond, where corresponding conditions for forming an amide bond include reacting a compound of formula 30 with a compound of formula 25 in the presence of a partner to form an amide bond, an aprotic solvent and a base to form a compound of formula I-1. Invention also relates to a method of producing a compound of formula I-1, comprising the steps of: a) reacting a compound of formula 5a under appropriate halogenation conditions, where the corresponding halogenation conditions involve reacting a compound of formula 5a with a halogenating agent and a base in the presence of a solvent to form a compound of formula 34; b) reacting a compound of formula 34 with a compound of formula 27 under suitable conditions for formation of an amide bond, where the corresponding conditions for forming an amide bond involve reacting a compound of formula 34 with a compound of formula 27 in an aprotic solvent while heating to form a compound of formula 28; c) reacting a compound of formula 28 under suitable deprotection conditions, where the corresponding deprotection conditions involve reacting a compound of formula 28 with an acid in the presence of a solvent to form a compound of formula 30; d) reacting a compound of formula 30 with a compound of formula 25 under suitable conditions for formation of an amide bond, where the corresponding amide bond formation conditions involve reacting a compound of formula 30 with a compound of formula 25 in the presence of a partner to form an amide bond, an aprotic solvent and a base to form a compound of formula I-1.

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EFFECT: novel methods of producing a compound of formula I-1, which can be used in medicine for use as an ATR protein kinase inhibitor.

15 cl, 12 tbl, 33 dwg, 19 ex