Scheme 3. Synthesis of compounds 22, 23, 26, 29–36. (a) (i) DIPEA, butan-1-ol (ii) TFA, DCM (iii) TBTU, DIPEA, DCM; (b) hydrazine hydrate, butan-1-ol, 14–43% (over steps a and b); (c) ammonium hydroxide, ethanol (EtOH), 83%; (d) DIPEA, butan-1-ol; (e) (i) methylhydrazine, DIPEA, butan-1-ol (for 24), 18% (over 2 steps) (ii) hydroxylamine. Hydrogen chloride (HCl), DIPEA, butan-1-ol (for 25), 10% (over 2 steps); (f) (i) (2-methoxyphenyl)boronic acid, potassium phosphate (K3PO4), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(ii), MeCN (ii) Boc2O, sodium hydride (NaH), THF, 92%; (g) DIPEA, N-methyl-2-pyrrolidone (NMP), 17%.
