Water → 7-Chloro-5-methyl-2-phenyl-1H-pyrrolo[3,2-b]pyridine

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Reaction Conditions

Reaction Steps

3-Amino-4-chloro-6-methyl-2-(2-phenyl ethynyl)pyridine (1.24 g, 5.1 mmol) was dissolved in anhydrous DMF (90 mL), CuI (150 mg, 0.8 mmol) was added and the mixture was heated at 110° C. for 18 h. The cooled mixture was poured into H2O (125 mL) and extracted with EtOAc (2×100 mL). The combined extracts were washed with H2O and brine, dried over MgSO4 and filtered through a plug of silica using CHCl3. The crude product was triturated with 20:1 hexanes:EtOAc, filtered, and dried under high vacuum to afford 600 mg (48%) of 7-chloro-5-methyl-2-phenyl pyrrolo-[3,2-b]pyridine. 1H NMR (DMSO-d6; 500 MHz): δ 2.40 (s, 3), 7.05 (s, 1), 7.16 (s,1), 7.38 (t, 1, J=5.2), 7.49 (m, 2), 8.02 (d, 2, J=7.2). MS m/z: 243 (M+H). This intermediate chloride (273 mg, 1.1 mmol) was taken up in 4:1 o-xylene/piperidine (10 mL) and heated to 140° C. in a Teflon-capped pressure tube for 7 d. The mixture was cooled to room temperature, diluted with H2O (125 mL) and extracted with EtOAc (2×100 mL). The combined organic layers were washed with H2O and brine, dried over MgSO4 filtered, and concentrated in vacuo. Chromatography on silica gel eluting with 10:1 CHCl3:MeOH afforded 244 mg (75%, 36% overall) of the title compound as a pale yellow solid. The product's 1H-NMR was identical to that obtained using Method A.

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