Water → N-[(Z)-1-azabicyclo[3.2.2]nonan-4-ylideneamino]-6-bromo-N-methylpyridin-2-amine

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Reaction Steps

A solution of 2-bromo-6-(1-methylhydrazinyl)pyridine (4.50 g, 22.2 mmol), 1-azabicyclo[3.2.2]nonan-4-one (3.00 g, 22.2 mmol) and p-toluenesulphonic acid (844 mg, 4.40 mmol) in toluene (140 mL) was heated under reflux, with water removal (azeotrope), for 4 h. The mixture was concentrated and made basic using saturated aqueous NaHCO3. The aqueous layer was extracted with methylene chloride (3×). The combined organic extracts were dried over Na2SO4, filtered and concentrated to dryness. The residue was purified by flash column chromatography (silica gel, 0%-100% solvent mixture B in methylene chloride; solvent mixture B=80:18:2 methylene chloride/methanol/concentrated ammonium hydroxide) to give the title compound (2.60 g, 36%) as a yellow oil: 1H NMR (500 MHz, CDCl3) δ 7.29 (t, J=8.0 Hz, 1H), 6.83 (d, J=7.0 Hz, 1H), 6.55 (d, J=8.5 Hz, 0.7H), 6.41 (d, J=8.5 Hz, 0.3 H), 3.20 (s, 3H), 3.17-2.94 (m, 7H), 2.80 (t, J=7.0 Hz, 0.6H), 2.73 (t, J=7.0 Hz, 1.4H), 1.89-1.85 (m, 3H), 1.74-1.60 (m, 1H).

Provenance & Evidence