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

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)+.

1. temperaturewere heated
2. temperatureto reflux for 16 h
3. filtrationThe reaction was filtered
4. customthe solution obtained
5. customwas used without further purification in the next step
6. customb) (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
7. extractionextracted into CH2Cl2
8. customthe concentrated residue purified by column chromatography on silica
9. washeluting with 1% MeOH/CH2Cl2

ORD record

ord-29a57da5719d4bf79af57ab1dea80b6e

Source dataset

uspto-grants-2006_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07022724B2