METHOD OF PRODUCING NITROGEN-CONTAINING HETEROCYCLIC COMPOUND AND INTERMEDIATE COMPOUND THEREOF Russian patent published in 2020 - IPC C07D239/48 

FIELD: chemistry.

SUBSTANCE: invention relates to improved versions of a method of producing intermediate compounds of formula [5] using a novel compound [1] and to an improved method of producing a compound of formula [13]. Compound of formula [13] exhibits high FLT3 inhibitory activity and can be used as an active ingredient of pharmaceutical products in treating leukaemia. Method of producing a compound of formula [5] , where R¹ is C_1-6 alkyl group which can be substituted, includes a step for reacting a compound of formula [1] or a salt thereof

with a compound of formula [2] or salt thereof, where R¹ has the definition given above, and X¹ is a chlorine atom, R² and R³ are a hydrogen atom or an amino protecting group, or R² and R³ together represent a phthaloyl group which can be substituted, or with hexamethylenetetramine, thereby obtaining a compound, formula [3] or its salt

, where R⁴ is , is a group represented by general formula [4], * denotes a binding position, R¹, R² and R³ have the definition given above or a hexamethylenetetraminium group; and then, if necessary, subjected to obtained compound or its salt of reaction of deprotection or hydrolysis reaction. Either method of producing a compound of general formula [5] includes (1) a step for reacting a compound of formula [6] or a salt thereof

,

where R¹ has the definition given above, X² and X³ is a leaving group, with 4-aminobenzonitrile or a salt thereof in the presence of hydrochloric acid, as a result of which a hydrochloride of a compound of general formula [7] and (2) is obtained, a step for reacting a compound of general formula [7] with a compound of formula [8], where X¹ is a chlorine atom, to obtain a compound of formula [1] or a salt thereof, (3) a step for reacting a compound of formula [1] with a compound of general formula [2] to obtain a compound of formula [3], or a salt thereof, followed by optionally, by deprotection or hydrolysis. Method of producing compound includes steps of producing compound [5], which is reacted with a compound of formula [9] or salt thereof

,

where R⁵ is an amino-protecting group, and X⁴ is a hydroxyl group or a leaving group, to obtain a compound of formula [10] or a salt thereof, (3) a step for deprotection of compound [10] to obtain a compound of formula [11], which then reacts with a compound of formula [12] or salt thereof

,

where R¹ has the definition given above, and R⁵ has the definition given above. Compound of the formula [14] corresponds to the general structural formula [1] wherein X¹ is chloro or [3], wherein R⁴ represents a group [4^a].

EFFECT: method simplifies the process by avoiding purification steps for removing triphenylphosphine oxide and increasing stability of the starting compounds.

10 cl, 11 ex