4-Methylmorpholine → (2S,3S,4S,5R,6R)-benzyl 6-((4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(1,1-dioxidothiomorpholino)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-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)benzoyl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate

Participants

Reaction Steps

A mixture of (2S,3S,4S,5R)-benzyl 3,4,5,6-tetrahydroxytetrahydro-2H-pyran-2-carboxylate (61.7 mg, 0.217 mmol), 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(1,1-dioxidothiomorpholino)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-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 (100 mg, 0.145 mmol), HATU (88 mg, 0.232 mmol) and N-methylmorpholine (0.048 mL, 0.434 mmol) in dioxane (3 mL) was stirred overnight at room temperature. The reaction mixture was filtered, the clear solution was purified by prep HPLC with acetonitrile/water/ammonium acetate to provide the desired product as white solid (20 mg, 14%). LCMS: m/e 957.7 (M+H)+, 2.36 min (method 6). 1H NMR (500 MHz, Acetic) δ 8.05 (d, J=8.2 Hz, 2H), 7.58-7.14 (m, 7H), 5.95 (d, J=7.6 Hz, 1H), 5.38 (d, J=4.6 Hz, 1H), 5.26 (s, 2H), 4.84 (s, 1H), 4.74 (s, 1H), 4.30 (d, J=9.5 Hz, 1H), 4.05-3.78 (m, 3H), 3.46 (d, J=11.9 Hz, 1H), 3.38-3.22 (m, 6H), 3.20-3.11 (m, 3H), 3.07 (br. s., 2H), 2.95 (dt, J=10.8, 5.5 Hz, 1H), 2.42-1.01 (m, 22H), 1.77 (s, 3H), 1.30 (s, 3H), 1.15 (s, 3H), 1.12 (s, 3H), 1.03 (s, 3H), 1.00 (s, 3H).

Provenance & Evidence