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0 °C

A mixture of 2,6-dibromopyridine (16.92 g, 71.4 mmol) and 2-amino-3-cyanopyridine (5.0 g, 42.0 mmol) in THF (150 ml) was cooled to below −30° C. before n-butyl lithium (33.6 ml, 84 mmol, 2.5 M in hexanes) was added dropwise while maintaining temperature below −30° C. On complete addition, the reaction mixture was stirred at 0° C. on an ice bath for 1.5 hours. The reaction was then quenched by the addition of 2 M HCl (until pH=˜1) while keeping the temperature below 15° C., and stirred at below 15° C. for 15 mins. Additional 2M HCl (50 ml) was added and the mixture extracted with EtOAc (2×150 ml), the acidic aqueous was cooled on an ice bath before being basified by addition of 2M NaOH, causing precipitation of a brown solid. Resulting suspension was left to stand overnight, then solid product collected by filtration, washed with water and dried by suction, then under high vacuum to leave crude title compound as a brown solid (6.52 g, 56%). 1H NMR (DMSO-d6) 6.65 (1H, dd), 7.79 (2H, s), 7.93-7.83 (4H, m), 7.99 (1H, t), 8.28 (1H, dd). ES+ 280.80.

1. additionwas added dropwise
2. temperaturewhile maintaining temperature below −30° C
3. additionOn complete addition
4. customThe reaction was then quenched by the addition of 2 M HCl (until pH=˜1)
5. customthe temperature below 15° C.
6. stirringstirred at below 15° C. for 15 mins
7. additionAdditional 2M HCl (50 ml) was added
8. extractionthe mixture extracted with EtOAc (2×150 ml)
9. temperaturethe acidic aqueous was cooled on an ice bath
10. additionbefore being basified by addition of 2M NaOH
11. customprecipitation of a brown solid
12. customResulting suspension
13. waitwas left
14. waitto stand overnight
15. filtrationsolid product collected by filtration
16. washwashed with water
17. customdried by suction