Nitric Acid → (S)-5-Amino-6-nitro-1,3-dihydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one

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Reaction Steps

To a suspension of (R)-5-amino-1′-{[2-(trimethylsilyl)ethoxy]methyl}-1,3-dihydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (28.7 g, 75.2 mmol, described in Intermediate 3) in CH2Cl2 (100 mL) was added trifluoroacetic anhydride (106 mL, 752 mmol). The mixture was stirred for 10 min, after which time the aniline had been converted to the corresponding trifluoroacetanilide. The resulting mixture was cooled in an ice-salt bath and 15.8 M nitric acid (5.0 mL, 79 mmol) was added dropwise over 15 min, keeping the reaction temperature at 10-12° C. After the addition, the reaction mixture was stirred for 30 min, then H2O (12 mL) was carefully added, followed by trifluoroacetic acid (100 mL) and CH2Cl2 (100 mL). The mixture was allowed to warm to ambient temperature and stirring was continued for 2 h, followed by concentration to dryness in vacuo. The residue was dissolved in MeOH (200 mL) and the solution was adjusted to pH 10 by addition of 10 N NaOH. Ethylene diamine (5 mL, 75 mmol) was added and the mixture was stirred at ambient temperature for 18 h, then diluted with H2O (200 mL). The resulting solid was isolated by filtration, washed with H2O, and dried in vacuo to give the title compound. MS: m/z=297 (M+1).

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