HCID 86713636, compound → HCID 71584786, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of Example D2 (0.100 g, 0.448 mmol) and prop-1-en-2-yl (5-(7-amino-1-ethyl-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluoro-4-methylphenyl)carbamate (0.142 g, 0.358 mmol) in dioxane (3 mL) was treated with 1-methylpyrrolidine (3 drops) and heated at 80° C. overnight. The mixture was treated with DMSO (2 drops) and heated at 80° C. for an additional 24 h. The mixture was cooled to RT, concentrated to dryness and purified via reverse-phase chromatography (MeCN/H2O with 0.1% TFA). The organics were removed under reduced pressure, the aqueous residue treated with satd. NaHCO3, extracted with EtOAc (2×) and the combined organics were washed with brine, dried over MgSO4 and concentrated to dryness to afford 1-(5-(7-amino-1-ethyl-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluoro-4-methylphenyl)-3-(4-fluoro-3-((4-methylpiperazin-1-yl)methyl)phenyl)urea (44 mg, 22% yield). 1H NMR (400 MHz, pyridine-d5): δ 9.87 (s, 1H), 8.89 (s, 1H), 8.71 (m, 1H), 8.60 (s, 1H), 7.97 (dd, J=6.5, 2.8 Hz, 1H), 7.79 (dt, J=8.7, 3.6 Hz, 1H), 7.64 (s, 1H), 7.26 (s, 2H), 7.15 (t, J=9.2 Hz, 1H), 7.07 (d, J=12.0 Hz, 1H), 6.56 (s, 1H), 4.17 (q, J=7.1 Hz, 2H), 3.58 (s, 2H), 2.53 (s, 4H), 2.30 (m, 7H), 2.13 (s, 3H), 1.16 (t, J=7.1 Hz, 3H); MS (ESI) m/z: 562.2 [M+H]+.

Provenance & Evidence