Reagents
and conditions: [i]
LiOH, THF/H2O, RT, 16 h; [ii] pyrrolidine, HATU, DMF, RT,
16 h, 36% over two steps; [iii] formic acid, CHCl3, 2 h,
reflux, 95%; [iv] amine, HATU, Et3N, DMF, RT, 16 h, 20–67%;
[v] R3NH2, R5CHO, methylisocyanide,
MeOH, RT, 16 h, 9–64%; [vi] formic acid, CHCl3,
2 h, reflux, 88%; [vii] 2-((2-(difluoromethoxy)benzyl)amino)-N-methylacetamide, HATU, Et3N, DMF, RT,
16 h, 77%; [viii] LiOH, THF/H2O, 40 °C, 16 h, 98%;
[ix] R1R2NH, HATU, Et3N, DMF, RT,
16 h, 18–80%.