Diisopropylamine → 2-(3-Hydroxyphenyl)-9-(1H-indol-4-YL)-8-oxo-8,9-dihydro-7H-purine-6-carboxamide

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Reaction Steps

Methyl 5-amino-2-chloro-6-(1-(phenylsulfonyl)-1H-indol-4-ylamino)pyrimidine-4-carboxylate. To a solution of methyl-2,4-dichloro-5-nitro-pyrimidine-6-carboxylate (2.0 g, 7.9 mmol) in tetrahydrofuran (20 mL) and diisopropylamine (2.3 mL, 13.05 mmol) was added amine (1.42 g, 5.22 mmol) in TETRAHYDROFURAN (5 mL) at −78° C. After warming to rt, only desired adduct was seen (MS (ESI) m/z 487.9[M+1]+). The reaction was diluted with EtOAc (100 mL) and washed with 5% HCl (aq, 100 mL). The EtOAc layer was separated, dried (Na2SO4), filtered, and concentrated. The crude 6-(1-benzenesulfonyl-1H-indol-4-ylamino)-2-chloro-5-nitro-pyrimidine-4-carboxylic acid methyl ester was subjected to silica gel chromatography (9:1 Hex in EtOAc) to afford 1.32 g (2.71 mmol, 52%) after concentration of the desired fractions. 6-(1-Benzenesulfonyl-1H-indol-4-ylamino)-2-chloro-5-nitro-pyrimidine-4-carboxylic acid methyl ester (1.32 g, 2.71 mmol) was then dissolved in AcOH (15 mL). To this solution was added Fe (s, 1.4 g). The mixture was stirred at 60° C. for 1H, after which LCMS showed the desired reduced product (MS (ESI) m/z 458.1 [M+1]+). The reaction was filtered and then concentrated. The crude residue was subjected to silica gel chromatography (4:1 Hex in EtOAc). Concentration of the desired fractions afforded the title compound (0.85 g, 1.86 mmol, 69%).

Provenance & Evidence