反应详情

A mixture of 4-(2-ethoxy-6-iodo-1H-1,3-benzodiazol-1-yl)pyrimidin-2-amine (150 mg, 0.394 mmol) and 7-ethynyl-5H,6H-cyclopenta[b]pyridin-7-ol (118 mg, 0.59 mmol) was dissolved in piperidine (1 mL). The solution was de-gassed with nitrogen for 2 mins. Tetrakis(triphenylphosphine)palladium(0) (36 mg, 0.031 mmol) and copper(I) iodide (6 mg, 0.031 mmol) were added and the resultant solution heated to 30° C. for 2 hr. The mixture was concentrated in vacuo, DCM (10 mL) added and re-concentrated in vacuo (twice). The residue was purified by column chromatography (Biotage, 0-10% MeOH gradient in DCM), followed by reverse phase preparative HPLC purification to give the title compound; 1H NMR (500 MHz, DMSO) delta 1.44 (3H, t, J=7.1 Hz), 2.36-2.42 (1H, m), 2.52-2.62 (1H, m), 2.83-2.95 (1H, m), 2.94-3.08 (1H, m), 4.63 (2H, q, J=7.0 Hz), 6.96 (1H, d, J=5.5 Hz), 7.08 (2H, s), 7.19-7.32 (2H, m), 7.44 (1H, d, J=8.2 Hz), 7.72 (1H, d, J=7.6 Hz), 8.13 (1H, s), 8.38 (1H, d, J=5.5 Hz), 8.44 (1H, d, J=4.8 Hz), 8.51 (1H, s); LC-MS: m/z=+413.05 (M+H)+.

1. customThe solution was de-gassed with nitrogen for 2 mins
2. concentrationThe mixture was concentrated in vacuo, DCM (10 mL)
3. additionadded
4. concentrationre-concentrated in vacuo (twice)
5. customThe residue was purified by column chromatography (Biotage, 0-10% MeOH gradient in DCM)
6. customfollowed by reverse phase preparative HPLC purification