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-1-(prop-1-en-2-yl)-3a-(2-(pyridazin-3-ylamino)ethylamino)-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-(methylsulfonyl)pyridine (0.024 g, 0.100 mmol) was used in place of 3-chloropyridazine. Purification of the crude Step 2 mixture by reverse phase preparative HPLC using Prep HPLC Method 10 gave the title compound as an off-white solid (10.6 mg, 11.9% yield over 2 steps) bis TFA salt. LCMS: m/e 728.5 (M+H)+, 2.22 min (method 11). 1H NMR (500 MHz, 1:1 mixture of CDCl3 and MeOD, MeOD lock) δ ppm 8.61 (d, J=1.8 Hz, 1H), 7.95-7.87 (m, 3H), 7.19 (d, J=8.2 Hz, 2H), 6.80 (d, J=8.9 Hz, 1H), 5.29 (d, J=4.6 Hz, 1H), 4.90 (s, 1H), 4.82 (br. s., 1H), 3.96-3.85 (m, 1H), 3.85-3.71 (m, 1H), 3.42 (br. s., 1H), 3.37 (s, 3H), 3.27-3.18 (m, 1H), 3.10 (s, 3H), 2.70 (br. s., 1H), 2.14 (dd, J=17.2, 6.3 Hz, 1H), 2.10-1.95 (m, 5H), 1.91-1.77 (m, 3H), 1.74 (s, 3H), 1.71 (d, J=17.4 Hz, 2H), 1.65-1.47 (m, 6H), 1.47-1.34 (m, 3H), 1.34-1.11 (m, 6H), 1.06 (s, 3H), 1.00 (s, 3H), 0.94 (s, 6H), 0.93 (s, 3H).

1. customThe title compound was prepared
2. customPurification of the crude Step 2 mixture by reverse phase preparative HPLC