Phosphorus oxychloride → 6-Methylimidazo[1,5-A]pyridine

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Reaction Conditions

Reaction Steps

In a round-bottomed flask, N-(5-methyl-pyridin-2-ylmethyl)-formamide (crude from step 2) was dissolved in toluene (30 ml) and phosphorus oxychloride (1.2 ml, 12.9 mmol) was added. The reaction mixture was stirred at 100° C. in an oil bath overnight then cooled to 0° C. and carefully quenched with ice. Aqueous 25% ammonium hydroxide was added until pH=˜9. The mixture was diluted with water and extracted with dichloromethane (2×). The organic layers were combined, dried over sodium sulfate, filtered and concentrated. The residue was absorbed on silica gel and chromatographed with EtOAc/hexanes (gradient 0-80% EtOAc) to give 386 mg (41%, 3 steps) of 6-methyl-imidazo[1,5-a]pyridine as a light brown solid. 1H NMR (CDCl3, 300 MHz): δ (ppm) 8.09 (s, 1H), 7.74 (s, 1H), 7.32-7.43 (m, 2H), 6.60 (dd, J=9.4, 1.1 Hz, 1H), 2.25 (d, J=1.1 Hz, 3H).

Provenance & Evidence