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. Author manuscript; available in PMC: 2023 Nov 24.
Published in final edited form as: J Med Chem. 2022 Nov 11;65(22):15238–15262. doi: 10.1021/acs.jmedchem.2c01170

Scheme 1. Six-Step Synthetic Route for 1H-Imidazo[4,5-c]quinolin-4-amine Derivatives with 2 Position and 4-Arylamino Substitutions (B), Including the Synthesis of a Common Diamino Intermediate 44 (A)a.

Scheme 1.

aReagents and conditions: (i) HNO3, 75 °C, 95%; (ii) PhPOCl2, 135 °C, 87%; (iii) 28% aq. ammonia, CH3CN, 50 °C, 97%; (iv) Fe powder, HCl, CH3CH2OH/H2O, 75 °C, 70%; (v) PPA, 120 °C; (vi) TCFH, NMI, ACN, 60 °C; (vii) NaOH, H2O:MeOH (1:1), 90 °C; (viii) Pd2(dba)3, tBuXPhos, t-BuONa, 1,4-dioxane, 100 °C, 5–51%, (ix) Pd(OAc)2, tBuXPhos, t-BuONa, H2O, 1,4-dioxane, 100 °C, 2–33%; (x) EtOH, microwave, 130 °C, 10–61%; (xi) 18, Et2Zn, CH2I2, 0 °C, 13%; (xii) 18, m-CPBA, CHCl3, 6–12%, 30 and 31 separated chromatographically; (xiii) 18, (CH3)2S·BH3, THF, NaOH, H2O2, 0 °C, 8–12%, 33 and 34 separated chromatographically; (xiv) 33/34, DMP, CHCl3, 23%; (xv) 36, Pd(OAc)2, CH2═CHCOOCH3, Et3N, 140 °C, 18%; (xvi) 35, Pd(Ph3P)2Cl2, 5-Cl-thien-2-yl-acetylene, CuI, Et3N, 80 °C, 10%.