N-(3-AMINO-QUINOXALIN-2-YL)-SULFONAMIDE DERIVATIVES AND THEIR USE AS PHOSPHATIDYLINOSITOL 3-KINASE INHIBITORS

摘要

Disclosed herein is a process for preparing N-(3-amino-quinoxalin-2-yl)-sulfonamide derivatives of formula I, wherein the substituents are as defined within the specification, comprising: Reacting an intermediate of formula 5 with an intermediate of formula NHRaRb or HO-C1-C6-alkylenene-NHRaRb to yield a compound of formula I(c) or I(d); or Reacting an intermediate of formula 8, with an intermediate of formula 9(1), 9(b), 9(c), 9(d), 9(e), 9(f) or 9(g);wherein: 9(a) is HOC(O)-C1-C6-alkylene-N(R7a)(R7b), wherein Ra is R7a or a N-protecting group that is Boc or Fmoc; 9(b) is HOC(O)R9a; 9(c) is HOC(O)NR11aR11b; 9(d) is HOC(O)OR13a; 9(e) is HOCCO)-C1-C6-alkylene-N(R18b)C(O)R18a; 9(f) is HOC(O)-C1-C6-alkylene-C(O)R20a; 9(g) is LG-S(O)2R-C1-C6-alkylene-N(R21b)Ra, wherein Ra is R21a or a N-protecting group that is Boc or Fmoc; to yield a compound of formula I(e);or Reacting an intermediate of formula 11 with an intermediate selected from NHR8R8a, NH(R10)-C1-C6-alkylene-N(R10a)R10b, a cyclic amine, NH(R14)N(R14a)(R14b), NHR16-C1-C6-alkylene-C(O)OR16a, and NH(R19)-C1-C6-alkylene-C(O)R19a, to yield a Compound of Formula I; or Reacting an intermediate of formula 12 with an intermediate of formula NH(R7b)R7a to yield a Compound of Formula I(f); or reacting an intermediate of formula 13, with an intermediate of formula (a) to yield a compound formula I(h); and optionally further resolving individual isomers. Also disclosed are intermediates useful in the process disclosed above, namely: N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide; and 3-amino-N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide.