1-Ethyl-4-(prop-2-ynyl)piperazine → N-(4-(2-(3-(4-ethylpiperazin-1-yl)prop-1-ynyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

Participants

Reaction Steps

Prepared from N-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (Example 12, Step A, 50 mg, 0.0845 mmol) and 1-ethyl-4-(prop-2-ynyl)piperazine (Example 18, Step A, 32.2 mg, 0.211 mmol) using the procedure described for Example 6, Step B. The crude was purified by preparative TLC (1 mm thickness, Rf=0.67), eluting with 10% MeOH (containing 7N NH3) in CHCl3. The product was obtained as a waxy solid (5 mg, 10%). HPLC: 100% purity (220 nm); LRMS (APCI−): 100% purity, 220 nm, m/z 614 (M−1) detected; 1H NMR (400 MHz, CDCl3) δ 10.04 (s, 1H), 8.49 (d, J=5 Hz, 1H), 8.31 (br s, 1H), 7.75 (m, 1H), 7.58 (s, 1H), 7.43 (m, 2H), 7.24 (m, 2H), 7.06 (m, 2H), 6.52 (d, J=5 Hz, 1H), 3.64 (m, 2H), 3.61 (s, 2H), 2.4-2.8 (m, 8H), 1.80 (m, 2H), 1.62 (m, 2H), 1.12 (m, 3H).

Provenance & Evidence