Reaction Steps
To a 0.25 L round bottom flask add [(2R,3R,4S,5R,6R)-3,4,5-triacetoxy-6-[4-methyl-3-[[4-(3-methylsulfonyloxypropoxy)phenyl]methyl]indol-1-yl]tetrahydropyran-2-yl]methyl acetate (7.2 g, crude), 1-[2-(4,9-diazaspiro[5.5]undecan-9-yl)-2-oxo-ethyl]-3-isobutyl-urea (12.28 mmol), acetonitrile (100 mL), and diisopropylethylamine (40.92 mmol). Heat at 80° C. for 16 hours then concentrate under reduced pressure. Add methanol (50 mL) and sodium methoxide (20.46 mmol, 30% solution in MeOH) and stir at room temperature for 1 hour. Quench by adding a small piece of dry ice. Concentrate under reduced pressure. Purify by reverse phase flash chromatography (400 g C18 cartridge) eluting with 5-80% water (0.1% formic acid) in acetonitrile (0.1 % formic acid) in three portions. Concentrate under reduced pressure to yield the title compound as a formic acid salt containing small impurities. Dissolve the salt in 7N ammonia in methanol (20 mL) then concentrate to form the free base. Purify the free base by flash chromatography (330 g silica gel cartridge) eluting with 5% 7N ammonia in methanol/dichloromethane. Concentrate the product fractions under reduced pressure to yield the title compound (1.75 g, 22.81%): MS (m/z): 746.6 (M+H). H1 NMR (400.31 MHz, CD3OD): δ 7.28 (d, J=8.4 Hz, 1H), 7.03 (d, J=8.4 Hz, 2H), 7.02 (s, 1H), 6.97 (t, J=8.8 Hz, 1H), 6.69 (d, J=7.2 Hz, 1H), 5.37 (d, J=9.2 Hz, 1H), 4.15 (s, 2H), 3.95 (t, J=6.0 Hz, 2H), 3.91 (d, J=1.6 Hz, 2H), 3.87-3.80 (m, 2H), 3.65 (dd, J=11.6, 5.6 Hz, 1H), 3.57-3.38 (m, 5H), 3.31 (bm, 2H), 2.90 (d, J=6.8 Hz, 2H), 2.46-2.13 (m, 8H), 1.88 (pentet, J=6.8 Hz, 2H), 1.68 (septet, J=6.8 Hz, 1H), 1.61-1.28 (m, 8H), 0.86 (d, J=6.8, 6H).
