Phosphorus trichloride → HCID 135423329, compound

Participants

Reaction Steps

To a suspension of sodium hydride (97%, 0.030 g, 1.25 mmol) in N,N-dimethylformamide (1.5 mL) was added N-(2-methoxyethyl)-2-oxoindoline-5-carboxamide (0.176 g, 0.75 mmol). The formed mixture was stirred for 5 min at room temperature followed by the addition of 4-[(6-chloro-1-oxidopyridin-3-yl)methyl]morpholine (0.114 g, 0.5 mmol). The resulting reaction mixture was set under an N2 atmosphere and stirred for 1 h at 120° C. and then concentrated in vacuo. The remaining N,N-dimethylformamide was removed by co-evaporation with toluene (1×). The residue was purified on a silica gel column using chloroform/methanol/triethylamine, (90:10:1), as the eluent. The material was dissolved in chloroform (4 mL), and phosphorus trichloride (0.275 g, 2.0 mmol) was added. The reaction mixture was stirred for 1 h at 60° C. and then concentrated in vacuo. The residue was purified on a silica gel column using chloroform/methanol/triethylamine, (90:10:1), as the eluent followed by further purification by washing with diethyl ether (3 mL) to give 0.050 g (24% yield) of the title compound as the base. The base (0.050 g, 0.12 mmol) was dissolved in chloroform/methanol, (1:1), and treated with HCl in diethyl ether (1 M) at 0° C. The resulting yellow crystals were collected by filtration and washed with diethyl ether to obtain 0.029 g (50% yield) of the title compound: 1H NMR (DMSO-d6, 400 MHz) δ 11.48 (br s, 1H), 10.74 (br s, 1H), 8.54 (br s, 1H), 8.27 (s, 1H), 8.11 (d, J=8.0 Hz, 1H), 8.03 (s, 1H), 7.87 (d, J=9.2 Hz, 1H), 7.59 (d, J=8.4 Hz, 1H), 6.98 (d, J=8.4 Hz, 1H), 4.29 (br s, 1H), 4.00 (d, J=11.2 Hz, 2H), 3.87 (d, J=11.2 Hz, 1H), 3.83 (d, J=12.4 Hz, 1H), 3.50 (br s, 4H), 3.38 (d, J=12.4 Hz, 2H), 3.32 (s, 3H), 3.13 (m, 2H); MS (EI) m/z 411 (M++1).

Provenance & Evidence