反应详情

The title compound was prepared following a similar procedure as described for the synthesis of 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-(2-(6-methylpyridazin-3-ylamino)ethylamino)-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoic acid, except 2-bromo-5-(methylthio)pyridine (0.020 g, 0.100 mmol) was used in place of 3-bromo-6-methylpyridazine. Iterative purification of the crude mixture by reverse phase preparative HPLC first using Prep HPLC Method 9 and then repurification by Prep HPLC Method 10 gave the title compound as a white glassy solid (5.2 mg, 5.9% yield) bis TFA salt. LCMS: m/e 696.5 (M+H)+, 2.34 min (method 11). 1H NMR (500 MHz, 1:1 mixture of CDCl3 and MeOD, MeOD lock) δ ppm 8.03 (d, J=1.8 Hz, 1H), 7.93-7.88 (m, J=8.2 Hz, 2H), 7.61-7.57 (m, 1H), 7.21-7.14 (m, J=8.2 Hz, 2H), 6.71 (d, J=8.9 Hz, 1H), 5.27 (dd, J=6.1, 1.5 Hz, 1H), 4.87 (s, 1H), 4.75 (br. s., 1H), 4.72 (br. s., 1H), 3.80-3.72 (m, 1H), 3.72-3.63 (m, 1H), 3.18-3.09 (m, 1H), 2.72-2.64 (m, 1H), 2.39 (s, 3H), 2.11 (dd, J=17.1, 6.4 Hz, 1H), 2.08-2.01 (m, 1H), 2.00-1.90 (m, 3H), 1.90-1.74 (m, 3H), 1.72 (s, 3H), 1.71-1.66 (m, 2H), 1.65-1.44 (m, 7H), 1.44-1.33 (m, 3H), 1.33-1.12 (m, 7H), 1.04 (s, 3H), 0.97 (s, 3H), 0.91 (br. s., 3H), 0.91 (br. s., 3H), 0.87 (s, 3H).

1. customThe title compound was prepared
2. customIterative purification of the crude mixture by reverse phase preparative HPLC first using Prep HPLC Method 9
3. customrepurification by Prep HPLC Method 10