Reacción #69782

Ecuación de reacción

2-amino-5-bromo-3-iodopyridine

triethylamine

1,1-dimethyl-2-propyn-1-ol

→

4-(2-amino-5-bromo-pyridin-3-yl)-2-methyl-but-3-yn-2-ol

Rendimiento 82.0%

Disolventes

dichloromethane

dichloromethane

dichloromethane

Condiciones de reacción

Tratamiento posterior

1. 1
   Lavadowashed with water (2×50 mL)
2. 2
   workup.ADDITIONThe organic phase was then treated with 1 M HCl (80 mL)
3. 3
   OtroThe layers were separated
4. 4
   Extracciónthe organic layer was extracted with 1 M HCl (20 mL)
5. 5
   workup.ADDITIONThe combined product containing aqueous layers
6. 6
   Lavadowere washed with dichloromethane (2×10 mL)
7. 7
   workup.ADDITIONThe pH of the aqueous layer was adjusted to pH 7-9 by the drop wise addition of sodium hydroxide solution (28% in water, 18 g)
8. 8
   workup.STIRRINGThe resulting suspension was stirred at 20° C. for 2 hours
9. 9
   Filtraciónthe crystals were then filtered off
10. 10
    Lavadowashed with water (2×20 mL)
11. 11
    OtroThe wet crystals were dried at 50° C./<30mbar

Procedimiento

A suspension of 2-amino-5-bromo-3-iodopyridine (10.0 g, 33.5 mmol), bis-(triphenyl-phosphine)-palladium(II)-dichloride (117 mg, 0.17 mmol), copper(I)iodide (79 mg, 0.41 mmol) and triethylamine (6.1 mL, 43.5 mmol) in dichloromethane (40 mL) was treated at 23 to 30° C. within 1 to 2 hours with a solution of 1,1-dimethyl-2-propyn-1-ol (3.70 g, 44 mmol) in dichloromethane (10 mL) and the resulting mixture was stirred at 25° C. for 3 hours. The mixture was diluted with dichloromethane (20 mL) and washed with water (2×50 mL). The organic phase was then treated with 1 M HCl (80 mL). The layers were separated and the organic layer was extracted with 1 M HCl (20 mL). The combined product containing aqueous layers were washed with dichloromethane (2×10 mL). The pH of the aqueous layer was adjusted to pH 7-9 by the drop wise addition of sodium hydroxide solution (28% in water, 18 g). The resulting suspension was stirred at 20° C. for 2 hours and the crystals were then filtered off and washed with water (2×20 mL). The wet crystals were dried at 50° C./<30mbar affording 6.99 g (82%) of 4-(2-amino-5-bromo-pyridin-3-yl)-2-methyl-but-3-yn-2-ol as a melted mass with a purity of 99.5% (HPLC, area %). 1H NMR (400 MHz, CDCl3): δ ppm 1.63 (s, 6H); 4.0 (br., 3H); 7.59 (d, J=2.4, 1H); 8.03 (d, J=2.4, 1H).

Fuente