On August 26, 2021, Dai, Guangxiu; Xiao, Kun published a patent.Synthetic Route of 87486-34-8 The title of the patent was Preparation of heteroaryl heterocyclic compounds as BTK inhibitors for the treatment of cancer, inflammatory and autoimmune diseases. And the patent contained the following:
The invention is related to the preparation of compounds I [X1, X2 = independently CH, N; or X1 = N, X2 is CR14; R14 = C1-6 alkyl; X3, X4 = independently C or N; Y1, Y2 = independently CR10, N; R10 = H, D, halo, CN, etc.; R1, R2 = independently , H, D, halo, C1-6 alkyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, phenyl; or R1CCR2 form a ring selected from cyclohexane, (un)substituted cyclopentane, benzene, pyridine, etc.; R3 = H, D, halo, C1-6 haloalkyl; R4 = H, CHO, CONH2, halo, CN, 3-hydroxyoxetan-3-yl, etc.; Cy = II, III; R11 = H, C1-6 alkyl, C3-6 cycloalkyl, wherein the C1-6 alkyl is optionally substituted with one or more deuterium or halo; U, V, W = independently N, CR12; R12 = H, D, halo; R5 = H, (un)substituted alkoxycarbonyl, Ph, Ph, 5-6 membered monocyclic heteroaryl, 8-10 membered bicyclic heteroaryl, etc.; with provisos], their pharmaceutically acceptable salts, solvates, racemic mixtures, enantiomers, a diastereomers and tautomers, to a method of in vivo or in vitro inhibiting the activity of BTK their use for the treatment of related diseases, especially cancer, inflammatory and autoimmune diseases and pharmaceutical compositions containing them. Thus, IV was prepared by Pd-coupling of 5-bromo-3-[[5-[ethyl(2-methoxyethyl)amino]pyridin-2-yl]amino]-1-methylpyridin-2(1H)-one (preparation given) with [3-(2-acetoxyethyl)-2-(7,7-dimethyl-1-oxo-1,6,7,8-tetrahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2-yl)pyridin-4-yl]boronic acid (preparation given) and basic hydrolysis of the resulting acetate. V (characterization data given) inhibited BTK in a biochem. assay (IC50 = 0.008μM) and in Ramos cells (IC50 = 0.004μM). V showed better pharmacokinetic parameters than that of the reference GDC-0853, displayed a dose-dependent antitumor activity in the TMD8 s.c. xenograft model, and complete tumor regression would be achievable by continuous daily dosing of compound V at 30 mg/kg. The therapeutic effect of V on a rat arthritis model induced by type II collagen was studied (data given). The experimental process involved the reaction of 3,5-Dibromo-1-methylpyrazin-2(1H)-one(cas: 87486-34-8).Synthetic Route of 87486-34-8
The Article related to heteroaryl heterocycle preparation btk inhibitor antitumor inflammation autoimmune disease, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazines and Quinoxalines (Including Piperazines) and other aspects.Synthetic Route of 87486-34-8