Triethylamine → 2-benzyl-5-(3-fluoro-4-(2-(3-(4-methylpiperazin-1-yl)prop-1-ynyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)pyrimidin-4(3H)-one

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-benzyl-5-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)pyrimidin-4(3H)-one (8.0 mg, 0.014 mmol), 1-methyl-4-(prop-2-ynyl)piperazine (Example 17, Step A; 5.0 mg, 0.036 mmol), copper(I) iodide (0.1 mg, 0.0007 mmol), and triethylamine (0.020 ml, 0.14 mmol) in THF (0.5 mL) was sparged with N2 for 5 minutes, and then Pd(PPh3)4 (1.0 mg, 0.0007 mmol) was added. The sealed reaction was stirred at 50° C. for 3 hours. The reaction mixture was purified directly by silica gel chromatography, eluting with 10:1 dichloromethane/methanol. The desired product (6.6 mg, 81%) was obtained as a pale yellow solid. 1H NMR (400 MHz, d6-DMSO) δ 8.58 (d, J=5.5 Hz, 1H), 8.29 (s, 1H), 7.93 (dd, J=1.9, 12.5 Hz, 1H), 7.81 (s, 1H), 7.74 (m, 1H), 7.54 (t, J=8.6 Hz, 1H), 7.39-7.32 (m, 4H), 7.29-7.24 (m, 1H), 6.76 (d, J=5.1 Hz, 1H), 3.94 (s, 2H), 3.68 (s, 2H), 2.55-2.46 (m, 8H), 1.23 (s, 3H). LRMS (ESI pos) m/e 566 (M+1).

Provenance & Evidence