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-(2-methylbut-3-yn-2-yl)piperidine (10.2 mg, 0.0676 mmol) using the procedure described for Example 6, Step B. The crude was purified by preparative TLC (1 mm thickness, Rf=0.34) eluting with 10% MeOH/DCM. A second purification by preparative TLC was conducted (0.5 mm thickness, Rf=0.49), eluting with 15% MeOH in EtOAc, in order to obtain product of adequate purity. The product was obtained as a beige powder (8 mg, 38%). HPLC: 98% purity (254 nm); LCMS (APCI−): 100% purity, 220 nm, m/z 613 (M−1) detected; 1H NMR (400 MHz, CDCl3) δ 10.04 (s, 1H), 8.48 (d, J=6 Hz, 1H), 8.15 (s, 1H), 7.74 (m, 1H), 7.55 (s, 1H), 7.45 (m, 2H), 7.24 (m, 2H), 7.07 (t, J=9 Hz, 2H), 6.50 (d, J=6 Hz, 1H), 2.66 (br s, 4H), 1.81 (m, 2H), 1.64 (m, 6H), 1.51 (m, 8H).

1. customThe crude was purified by preparative TLC (1 mm thickness, Rf=0.34)
2. washeluting with 10% MeOH/DCM
3. customA second purification by preparative TLC
4. washeluting with 15% MeOH in EtOAc, in order
5. customto obtain product of adequate purity