Phosphoramidic acid, ion(2-) → (2S)-benzyl 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 100 mg (0.339 mmol) in 5 mL of THF, was added tert-BuMgCl 0.68 mL (0.68 mmol), followed by (2S)-benzyl 2-(chloro(naphthalen-1-yloxy)phosphorylamino)propanoate 273 mg (0.68 mmol), in 5 mL of THF. After work up and silica gel column chromatography, 131 mg of (2S)-benzyl 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 58% yield, as an off-white solid. MS (ES+) m/e: 663.23 (MH+, 100%); Accurate mass: C32H36N6O8P calculated: 663.2332. found 663.2341.

Provenance & Evidence