Pyridine → HCID 86269228, compound

Participants

Reaction Steps

A 0° C. solution of phosgene (15% in toluene, 1.41 mL, 2.003 mmol) in DCM (5 mL) was treated drop-wise with a solution of Example B18 (61 mg, 0.534 mmol) and pyridine (0.2 mL, 2.473 mmol) in DCM (5 mL), warmed to RT, stirred for 2 h, then concentrated to dryness. The residue was dissolved in DCM (5 mL), cooled to 0° C., treated with a solution of 6-methyl-5-((2-(4-(4-methylpiperazin-1-yl)phenyl)pyridin-4-yl)oxy)pyridin-2-amine (0.10 g, 0.266 mmol) and DIEA (0.2 mL, 1.145 mmol) in DCM (5 mL), warmed to RT and stirred overnight. The mixture was treated with 1N NaOH, extracted with EtOAc (3×) and the combined organics were washed with 1N NaOH, then brine, dried over Na2SO4, concentrated to dryness and purified via reverse-phase chromatography (MeCN/H2O with 0.1% TFA). The organics were removed under reduced pressure and the aqueous residue was treated with K2CO3 and extracted with 5:1 DCM/THF (3×). The combined organics were dried over Na2SO4 and concentrated to dryness to afford 3-ethyl-N-(6-methyl-5-((2-(4-(4-methylpiperazin-1-yl)phenyl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide (54 mg, 39%). 1H NMR (400 MHz, DMSO-d6): δ 10.90 (s, 1 H), 8.42 (d, J=5.6 Hz, 1 H), 7.92-7.86 (m, 3 H), 7.62 (d, J=8.9 Hz, 1 H), 7.32 (d, J=2.4 Hz, 1 H), 6.97 (d, J=8.8 Hz, 2 H), 6.63 (dd, J=5.7, 2.3 Hz, 1 H), 3.80 (t, J=8.3 Hz, 2 H), 3.46 (t, J=8.2 Hz, 2 H), 3.26-3.25 (m, 2 H), 3.20 (s, 4 H), 2.43 (s, 4 H), 2.25 (s, 3 H), 2.21 (s, 3 H), 1.09 (t, J=7.2 Hz, 3H); MS (ESI) m/z: 516.3 (M+H+).

Provenance & Evidence