反应详情

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, 20 mg, 0.0338 mmol) and 1-methyl-4-(2-methylbut-3-yn-2-yl)piperazine (11.2 mg, 0.0676 mmol) using the procedure described for Example 6, Step B. The crude was purified by preparative TLC (1 mm thickness, Rf=0.16) eluting with 10% MeOH/DCM. The compound was re-purified by preparative TLC (0.5 mm thickness, Rf=0.84) eluting with 15% MeOH (containing 7N NH3) in CHCl3, to obtain product of adequate purity. The product was obtained as a beige powder (4 mg, 18%). HPLC: 95% purity (220 nm); LCMS (APCI−): 100% purity, 220 nm, m/z 629 (M−1) detected; 1H NMR (400 MHz, CDCl3) δ 9.95 (s, 1H), 8.49 (d, J=5 Hz, 1H), 8.40 (br s, 1H), 7.73 (m, 1H), 7.54 (s, 1H), 7.44 (m, 2H), 7.21 (m, 2H), 7.06 (t, J=9 Hz, 2H), 6.54 (d, J=5 Hz, 1H), 2.84 (m, 4H), 2.65 (m, 4H), 2.39 (s, 3H), 1.82 (m, 2H), 1.64 (m, 2H), 1.51 (s, 6H).

1. customThe crude was purified by preparative TLC (1 mm thickness, Rf=0.16)
2. washeluting with 10% MeOH/DCM
3. customThe compound was re-purified by preparative TLC (0.5 mm thickness, Rf=0.84)
4. washeluting with 15% MeOH (containing 7N NH3) in CHCl3
5. customto obtain product of adequate purity