3-Methoxypropylamine → 6-chloro-N-(3-methoxypropyl)-3-nitropyridin-2-amine

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Reaction Steps

2,6-Dichloro-3-nitropyridine (3.29 mmol, 0.635 g) was added to an oven dried 50 mL round-bottomed flask equipped for stirring under nitrogen. Dichlormethane (12 mL) and triethylamine (3.62 mmol, 0.504 mL) were added and the resultant solution was cooled to −15° C. with an acetone/ice bath. 3-methoxypropan-1-amine (3.29 mmol, 0.337 mL) was then added drop-wise via syringe and the resultant solution was stirred at −15° C. for 0.5 hr. The acetone/ice bath was removed and the reaction was allowed to warm to room temperature and stir for 0.5 hr. The reaction solution was poured into water and extracted twice with dichloromethane (50 mL). The organic layer was collected and subsequently dried with anhydrous Na2SO4 and filtered. This filtrate was collected, concentrated, and dried in-vacuo affording an orange oil. This material was then purified by chromatography on silica gel (20% ethyl acetate/hexanes) to afford 6-chloro-N-(3-methoxypropyl)-3-nitropyridin-2-amine (33A) as a yellow solid (3.01 mmol, 0.740 g, 92% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.79-1.89 (m, 2H) 3.00 (s, 3H) 3.43 (t, J=6.06 Hz, 2H) 3.53-3.61 (m, 2H) 6.77 (d, J=8.59 Hz, 1H) 8.42 (d, J=8.08 Hz, 1H). ESI-MS: m/z 246.2 (M+H)+.

Provenance & Evidence