Phosphoramidic acid, ion(2-) → (2S)-((S)-1-phenylethyl) 2-((((2S,4R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-4-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(naphthalen-1-yloxy)phosphorylamino)propanoate

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Reaction Steps

Using the general procedure for the synthesis of nucleoside 5′-phosphoramidates (Method A), to a solution of (3R,5S)-2-(2-amino-6-methoxy-9H-purin-9-yl)-5-(hydroxymethyl)-3-methyl-tetrahydrofuran-3-ol 93 mg (0.315 mmol) in 5 mL of THF was added tert-BuMgCl 0.63 mL (0.63 mmol) followed by (2S)-((S)-1-phenylethyl) 2-(chloro(naphthalen-1-yloxy)phosphorylamino)propanoate 282 mg (0.63 mmol) in 5 mL of THF. After work up and silica gel column chromatography, 40 mg of (2S)-((S)-1-phenylethyl) 2-((((2S,4R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-4-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(naphthalen-1-yloxy)phosphorylamino)propanoate was obtained in a 19% yield, as an off-white solid. MS (ES+) m/e: 677.25 (MH+, 100%); Accurate mass: C33H38N6O8P calculated: 677.2489. found 677.2511.

Provenance & Evidence