METHOD OF IBRUTINIB PRODUCING Russian patent published in 2020 - IPC C07D487/04 

FIELD: chemistry.

SUBSTANCE: invention relates to improved versions of a method of producing Ibrutinib using novel intermediate compounds. Ibrutinib is an inhibitor of Bruton’s tyrosine kinase and is used for treating lymphoma and chronic lymphocytic leukemia. Method according to the present invention involves step 1 involving reacting a compound of formula 1 with a compound of formula 2 in the presence of a base to form a compound of formula 3

and step 2: subsequent reaction of the compound of formula 3 with a compound of formula 4 in the presence of a base and a catalyst to obtain Ibrutinib

wherein X₁ is independently selected from a group consisting of Cl, Br and I, preferably Cl and Br; X₂ is independently selected from a group consisting of Cl and Br; R' is selected from group consisting of and X₃ is independently selected from a group consisting of Cl, Br and I, preferably Cl and Br. Embodiment of the method of producing Ibrutinib involves carrying out step 1 by reacting a compound of formula 1 with a compound of formula 4 in the presence of a base and a catalyst to obtain a compound of formula 8

and step 2: reacting a compound of formula 8 with a compound of formula 2-1 in the presence of a base to obtain ibrutinib

in the method using readily available starting compounds.

EFFECT: method does not require the use of chromatographic purification, which leads to its simplification and cheapening; and products are obtained with high output of up to 90 % and high chemical purity of up to 98_5 %.

19 cl, 17 ex