Water → 2-Bromo-6-(bromomethyl)pyridine

Participants

Reaction Steps

A mixture of 2-bromo-6-methylpyridine (5.7 ml), NBS (8.9 g) and benzoyl peroxide (50 mg) in CCl4 (50 ml) were heated to reflux for 16 h. The reaction was filtered and the solution obtained was used without further purification in the next step. 1H NMR (400 MHz, CDCl3) δ 7.56 (1H, t, J=7.8 Hz), 7.45–7.40 (1H, m), 7.28 (1H, d, J=8.2 Hz), 4.50 (2H, s). b) (6-Bromopyridin-2-ylmethyl)dimethylamine 2-Bromo-6-bromomethyl-pyridine and NHMe2 (10 ml of 2M solution in THF) were reacted at RT for 16 h. The reaction mixture was poured into H2O, extracted into CH2Cl2 and the concentrated residue purified by column chromatography on silica, eluting with 1% MeOH/CH2Cl2 to give the title compound (440 mg). 1H NMR (400 MHz, CDCl3) δ 7.53 (1H, t, J=7.6 Hz), 7.40 (1H, d, J=7.5 Hz), 7.36 (1H, d, J=7.8 Hz), 3.57 (2H, s), 2.29 (6H, s). c) Dimethyl-{6-[3-(5-methyl-3-phenyl-isoxazol-4-yl)-5H-[1,2,4]triazolo[3,4-α]isoindol-8-yl]pyridin-2-ylmethyl}amine Prepared in a similar manner to Example 26 using (6-bromopyridin-2-ylmethyl)-dimethylamine to give the title compound (40 mg, 39%). 1H NMR (360 MHz, CDCl3) δ 8.63 (1H, d, J=1.1 Hz), 8.13 (1H, dd, J=8.1, 1.5 Hz), 7.78 (1H, t, J=7.7 Hz), 7.67 (1H, d, J=7.7 Hz), 7.56–7.54 (2H, m), 7.47–7.34 (5H, m), 4.06 (2H, s), 3.70 (2H, s), 2.73 (3H, s), 2.37 (6H, s), m/z (ES+) 449 (M+H)+.

Provenance & Evidence