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Reagents and conditions: (a) POCl3, 80 °C, 1 h, 70%; (b) NaOtBu, MeOH or morpholine, n-BuOH, 80 °C, 12 h, 60–100%; (c) HCCR1, CuI, Pd(PPh3)2Cl2, TEA, THF, 50 °C, 12 h, 19–61%; (d) KOH, MeOH, rt, 30 min, 94%; (e) 4, hydroxylamine-O-sulfonic acid, KOH, NaHCO3, H2O, DCM, 70 °C → rt, 12 h, 40–84%; (f) NH2R3, n-BuOH, 150 °C, 2 h, 11–90%; (g) NH2R3, Pd(OAc)2, BINAP or xantphos, Cs2CO3, dioxane, 160 °C, 1 h, 6–70%.
