Reaction Steps
To a stirred solution of (1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-9-acetoxy-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysene-3a-carboxylic acid (0.336 g, 0.674 mmol) (Prepared as described in J. Med. Chem. 2009. 52, 3248-3258) in DCM (1 ml) Oxolyl chloride (0.58 ml, 6.746 mmol) in DCM (3.15 ml) was added at 0° C. and stirred at room temperature for about 3 hours and completion of the reaction monitored by TLC then the solvent was evaporated under nitrogen atmosphere and dissolved in DCM (4 ml), which was added to the above stirred solution of ((1S,3R)-3-amino-2,2-dimethylcyclobutyl)(pyrrolidin-1-yl)methanone (step 2, 0.264 g, 1.349 mmol) at 0° C. and allowed to stir at room temperature for about 16 hours. After completion of the reaction (monitored by TLC), the reaction mixture was diluted with DCM and washed with aqueous 1N HCl, then washed with water and brine, and dried over Na2SO4, the solvent was evaporated and purified by silica gel column (100-200 mesh, elution 15% EtOAc in hexane) to afford the title compound as an off white solid. Wt: 0.350 g: Yield: 76.7%; 1H NMR (300 MHz, CDCl3): δ 6.28 (d, 1H), 4.72 (s, 1H), 4.58 (s, 1H), 4.51-4.06 (m, 2H), 3.56-3.27 (m, 8H), 3.18-3.08 (m, 1H), 2.91-2.74 (m, 2H), 2.60-2.46 (m, 2H), 2.37-2.20 (m, 3H), 2.08 (s, 3H), 1.99-1.11 (m, 26H), 1.00-0.75 (s, 18H); Mass: [M+Na]+ 699 (100%); IR (KBr, cm−1): 3268, 3077, 2955, 2873, 1734, 1716, 1618, 1549, 1455, 1452, 1371, 1344, 1242, 1180, 1150, 1033, 980, 869; M.R: 94.9° C.-101.2° C.
