1-Methylpiperazine → HCID 90403793, compound

Participants

Reaction Steps

A solution of Example A2 (0.15 g, 0.561 mmol) in THF (3 mL) was treated with TEA (0.114 g, 1.122 mmol) and 2-chloroacetyl isocyanate (0.107 g, 0.898 mmol), stirred at RT for 2 h, treated with N-methylpiperazine (0.112 g, 1.122 mmol) and stirred at RT for 4 h. The mixture was diluted with EtOAc, stirred for several minutes, the solids removed via filtration and the filtrate concentrated to dryness and purified via silica gel chromatography (NH4OH/MeOH/DCM). The material was suspended in 2:1 EtOAc/DCM and the solid was removed via filtration and discarded. The filtrate was concentrated to dryness and treated with 3:2 EtOAc/Hex. The mixture was briefly sonicated. The solid was collected via filtration, dissolved in MeCN/H2O, frozen and lyophilized to afford N-((5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)-2-(4-methylpiperazin-1-yl)acetamide (76 mg, 30%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 10.88 (s, 1H), 10.48 (br s, 1H), 8.37 (d, J=5.7 Hz, 1H), 8.27-8.24 (m, 2H), 8.07-8.00 (m, 1H), 7.96 (d, J=0.7 Hz, 1H), 7.74 (dd, J=9.0, 2.9 Hz, 1H), 7.23 (d, J=2.4 Hz, 1H), 6.70 (dd, J=5.7, 2.4 Hz, 1H), 3.84 (s, 3H), 3.22 (s, 2H), 2.51 (m, 4H), 2.35 (m, 4H), 2.15 (s, 3H); MS (ESI) m/z: 451.2 (M+H+).

Provenance & Evidence