Cesium carbonate → 3-(3-(2,4-Difluoro-5-(3-phenylureido)phenyl)-1-ethyl-2-oxo-1,2-dihydro-1,6-naphthyridin-7-yl)-1,1-dimethylurea

Participants

Reaction Conditions

Reaction Steps

A mixture of 1-(5-(7-chloro-1-ethyl-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2,4-difluorophenyl)-3-phenylurea (211 mg, 0.464 mmol), Cs2CO3 (453 mg, 1.392 mmol), N,N-dimethylurea (204 mg, 2.319 mmol) and Xantphos (81 mg, 0.139 mmol) in dioxane (5 mL) was sparged with Ar, treated with Pd2(dba)3 (64 mg, 0.070 mmol) and heated at 100° C. for 4 h. The mixture was cooled to RT, treated with EtOAc, DMF and 50% satd. NaHCO3 and the solids removed via filtration through diatomaceous earth. The layers of the filtrate were separated, the organic layer washed with 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, the aqueous residue treated with satd. NaHCO3 and stirred. The resulting solid was collected via filtration and dried to afford 3-(3-(2,4-difluoro-5-(3-phenylureido)phenyl)-1-ethyl-2-oxo-1,2-dihydro-1,6-naphthyridin-7-yl)-1,1-dimethylurea (47 mg, 33% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.21 (s, 1H), 9.03 (s, 1H), 8.66 (s, 1H), 8.57 (s, 1H), 8.17 (dd, J=9.1, 7.8 Hz, 1H), 8.01 (d, J=2.1 Hz, 2H), 7.45-7.38 (m, 3H), 7.26 (t, J=7.8 Hz, 2H), 6.96 (t, J=7.4 Hz, 1H), 4.18 (q, J=7.3 Hz, 2H), 2.97 (s, 6H), 1.24 (t, J=7.1 Hz, 3H); MS (ESI) m/z: 507.2 [M+H]+.

Provenance & Evidence