Sodium hydride → 2-bromo-6-(5-methoxy-1-methyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazine

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Reaction Steps

5-Bromo-3-((5-methoxy-1-methyl-1H-indol-3-yl) ethynyl)pyrazin-2-amine (3.25 g, 9.10 mmol) in DMF (35 mL) was treated with NaH (60% dispersion in mineral oil, 0.36 g, 9.1 mmol). After about 5 h at ambient temperature, the mixture was treated with another portion of NaH (60% dispersion in mineral oil, 0.036 g, 0.91 mmol) and stirred for about 16 h. The mixture was concentrated and stirred with water (50 mL) and EtOAc (40 mL). The mixture was filtered and the solids were washed until an insoluble tar remained. The filtrate layers were separated and the organic layer was dried over anhydrous MgSO4, filtered, and concentrated. The material was dissolved in a minimum amount of warm DMF and purified by silica gel chromatography (120 g silica gel column) eluting with 95:5 DCM/MeOH. The product-containing fractions were combined and concentrated to give an oil which was purified by silica gel chromatography (120 g silica column) eluting with EtOAc. The product-containing fractions were combined and concentrated to give an oily residue which was triturated with EtOAc (20 mL) then filtered to give a yellow solid. The material was dried to give 2-bromo-6-(5-methoxy-1-methyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazine (1.48 g, 45%): LC/MS (Table 2, Method a) Rt=2.50 min; MS m/z: 357 (M+H)+.

Provenance & Evidence