Trimethylacetamide → HCID 90410317, compound

Participants

Reaction Steps

To a stirring suspension of trimethylacetamide (0.115 g, 1.141 mmol) in 1,2-dichloroethane (5 mL) at RT was added oxalyl chloride (0.100 mL, 1.141 mmol). The mixture was stirred 1 h at RT and then at 90° C. for 1 h. The mixture was cooled to RT and added slowly to a stirring solution of N-(4-((6-aminopyridin-3-yl)oxy)pyridin-2-yl)-4-benzylpiperazine-1-carboxamide (0.355 g, 0.878 mmol) in CH2Cl2 (15 mL). Solids precipitated and the suspension was stirred overnight at RT. DIEA (0.6 mL) was added and the resulting solution stirred 45 min. It was washed with H2O (2×), brine (1×), dried (MgSO4), and evaporated. The crude product was purified by silica gel chromatography (0-6% MeOH/CH2Cl2) and then re-purified by silica gel chromatography (0-10% MeOH/EtOAc) to afford 4-benzyl-N-(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)piperazine-1-carboxamide (0.151 g, 32%) as an off-white brittle foam. 1H NMR (400 MHz, DMSO-d6): δ 11.22 (s, 1H), 10.44 (s, 1H), 9.24 (s, 1H), 8.23 (d, J=2.9 Hz, 1H), 8.11 (d, J=5.7 Hz, 1H), 8.08 (d, J=9.1 Hz, 1H), 7.71 (dd, J=9.0, 2.9 Hz, 1H), 7.36 (d, J=2.4 Hz, 1H), 7.28-7.26 (m, 5H), 6.61 (dd, J=5.7, 2.4 Hz, 1H), 3.46 (s, 2H), 3.40 (m, 4H), 2.31 (t, J=4.7 Hz, 4H), 1.21 (s, 9H); MS (ESI) m/z: 532.3 (M+H+).

Provenance & Evidence