1,4-anhydro-2-O-(2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-5,8-dichloro-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-deoxy-L-threo-pentitol → 1,4-anhydro-3-deoxy-2-O-{5,8-dichloro-2-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl}-L-threo-pentitol

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Reaction Steps

A solution of 1,4-anhydro-2-O-(2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-5,8-dichloro-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-deoxy-L-threo-pentitol (296o, 36 mg, 0.065 mmol) in trifluoroacetic acid (2 mL) was stirred at room temperature for three hours. The volatiles were removed under vacuum, and the residue partitioned between ethyl acetate (20 mL) and saturated aqueous sodium bicarbonate (20 mL). The aqueous layer was back-extracted with ethyl acetate (2×20 mL). The combined organic extracts were dried over sodium sulfate, concentrated, and purified by silica gel chromatography (eluting with a gradient of 0-10% methanol in ethyl acetate) to yield 1,4-anhydro-3-deoxy-2-O-{5,8-dichloro-2-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl}-L-threo-pentitol (Example 296, 12 mg, 40% yield), as a solid, after lyophilization. 1H NMR (400 MHz, methanol-d4) δ 7.14 (s, 1H), 6.00 (s, 1H), 4.93-5.02 (m, 1H), 4.64 (s, 2H), 3.95-4.06 (m, 2H), 3.85 (dd, J=10.39, 4.28 Hz, 1H), 3.56-3.64 (m, 1H), 3.49-3.55 (m, 1H), 3.38 (t, J=6.17 Hz, 2H), 2.80 (t, J=6.24 Hz, 2H), 2.36 (ddd, J=14.09, 7.79, 6.60 Hz, 1H), 2.18 (s, 3H), 2.14 (s, 3H), 1.84 (dd, J=13.94, 5.50 Hz, 1H).

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