On November 15, 2007, Dorsey, Bruce D.; Milkiewicz, Karen L.; Pippin, Douglas A.; Theroff, Jay P.; Underiner, Theodore L.; Weinberg, Linda; Zificsak, Craig A. published a patent.Formula: C8H9BrN2O2 The title of the patent was Preparation of pyridopyrazine derivatives as ALK and c-Met inhibitors. And the patent contained the following:
Title compounds I [ A = N or CH; X = -L2G1L3G2L4R7 or R8, wherein G1 and G2 independently = bond, (un)substituted (hetero)aryl or heterocycloalkyl; R7 = (un)substituted alkyl, alkenyl, alkynyl, (hetero)aryl or (hetero)cycloalkyl; R8 = H, halo, CN or CO2H; L1-4 independently = bond, alkyl-C(O)-alkyl, alkyl-C(O)O-alkyl, alkyl-O-alkyl, alkyl, alkenyl, alkynyl, etc.; R1 = (un)substituted (hetero)cycloalkyl or (hetero)aryl; R2 and R3 independently = H, OH or alkyl; R2 and R3 together may form a carbonyl group; R4, R5 and R6 independently = H or alkyl; R4 and R5 together may form a carbonyl group, or one of R4 and R5 forms a double bond with R6], and their pharmaceutically acceptable salts, are prepared and disclosed as Anaplastic Lymphoma Kinase (ALK) and c-Met inhibitors. Thus, e.g., II was prepared by acylation of 7-iodo-1,2,3,4-tetrahydropyrido[2,3-b]pyrazine (preparation given) with benzoyl chloride followed by Suzuki coupling reaction with (4-ethoxycarbonylphenyl)boronic acid to generate intermediate 4-(1-benzyl-1,2,3,4-tetrahydropyrido[2,3-b]pyrazin-7-yl)benzoic acid Et ester followed by hydrolysis and amidation with (S)-(+)-1-[(2-pyrrolidinyl)methyl]pyrrolidine to provide II as trifluoroacetate salt. All exemplar compounds were tested for their ability to inhibit the kinase activity for ALK and c-Met. For instance, II exhibited IC50 values ranging from 0.1 to 1 μM for ALK and c-Met kinase inhibition, resp. As inhibitors of ALK and/or c-Met, I may be used to treat ALK- or c-Met-mediated disorders or conditions. The experimental process involved the reaction of 3-((6-Bromopyridin-2-yl)amino)propanoic acid(cas: 68638-67-5).Formula: C8H9BrN2O2
The Article related to pyridopyrazine preparation anaplastic lymphoma kinase alk cmet inhibitor, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazines and Quinoxalines (Including Piperazines) and other aspects.Formula: C8H9BrN2O2