反应详情

Using the method described in Example 49, 3-cyclohexyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid (Intermediate 33) and 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-ylamine (Intermediate 4) afforded 3-cyclohexyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-propionamide as a white solid as a mixture of diastereomers (2.01 g, 94%); ES+-HRMS m/e calcd for C28H33N5O5F2 [M+H+] 558.2523 found 558.2521. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.80-1.19 (m, 6H) 1.23 (s, 3H) 1.29 (s, 3H) 1.61 (br s, 5H) 1.75-1.91 (m, 1H) 2.06-2.21 (m, 1H) 3.71 (dd, J=8.5, 5.8 Hz, 1H) 3.90-4.21 (m, 3H) 4.33 (quin, J=5.8 Hz, 1H) 5.52 (dd, J=10.9, 3.9 Hz, 1H) 6.02 (d, J=2.7 Hz, 1H) 6.36 (d, J=2.1 Hz, 1H) 7.28-7.54 (m, 3H) 7.57 (d, J=2.1 Hz, 1H) 8.27 (d, J=2.7 Hz, 1H) 10.83 (s, 1H).