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)piperidin-4-yl)methanol (12.3 mg, 0.0676 mmol) using the procedure described for Example 6, Step B. The crude was purified by preparative TLC (1 mm thickness, Rf=0.63) eluting with 20% MeOH/DCM. The compound required a second purification by preparative TLC (0.5 mm thickness, Rf=0.11), eluting with 15% MeOH in EtOAc, to obtain product of adequate purity. The product was obtained as a beige powder (5 mg, 23%). HPLC: 99% purity (254 nm); LCMS (APCI−): 100% purity, 220 nm, m/z 643 (M−1) detected; 1H NMR (400 MHz, CDCl3) δ 10.08 (s, 1H), 8.49 (d, J=5 Hz, 1H), 8.23 (s, 1H), 7.78 (m, 1H), 7.56 (s, 1H), 7.45 (m, 2H), 7.27 (m, 2H), 7.07 (t, J=9 Hz, 2H), 6.53 (d, J=5 Hz, 1H), 3.53 (d, J=6 Hz, 2H), 3.22 (br s, 2H), 2.31 (br s, 2H), 1.82 (m, 4H), 1.62 (m, 10H), 1.36 (m, 2H).

1. customThe crude was purified by preparative TLC (1 mm thickness, Rf=0.63)
2. washeluting with 20% MeOH/DCM
3. customa second purification by preparative TLC (0.5 mm thickness, Rf=0.11)
4. washeluting with 15% MeOH in EtOAc
5. customto obtain product of adequate purity