Reacción #537049

Ecuación de reacción

O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate

N-(2-aminopyridin-4-yl)-2,6-dichlorobenzamide

5-bromothiophene-2-carboxylic acid

diisopropylethylamine

→

desired product

Rendimiento 30.0%

2-Bromo-N-(4-(2,6-dichlorobenzamido)pyridin-2-yl)thiazole-5-carboxamide

Rendimiento 30.0%

Disolventes

N,N-dimethylformamide

Condiciones de reacción

Tratamiento posterior

1. 1
   ConcentraciónThe mixture was then concentrated under reduced pressure
2. 2
   Otrothe residue was partitioned between EtOAc (30 mL) and 1 N NaOH (20 mL)
3. 3
   ExtracciónThe aqueous layer was extracted with EtOAc (2×30 mL)
4. 4
   SecadoThe combined organic extracts were dried over Na2SO4
5. 5
   Concentraciónconcentrated under reduced pressure
6. 6
   OtroThe redidue was purified by silica gel column chromatography (0-40% EtOAc/hexane)

Procedimiento

To a solution of N-(2-aminopyridin-4-yl)-2,6-dichlorobenzamide (282 mg, 1.00 mmol), 5-bromothiophene-2-carboxylic acid (624 mg, 3.0 mmol) in N,N-dimethylformamide (5 mL) was added diisopropylethylamine (700 μL, 4.00 mmol), followed by O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (1.14 g, 3.0 mmol). The mixture was heated at 60° C. for 24 hours. The mixture was then concentrated under reduced pressure and the residue was partitioned between EtOAc (30 mL) and 1 N NaOH (20 mL). The aqueous layer was extracted with EtOAc (2×30 mL). The combined organic extracts were dried over Na2SO4, and concentrated under reduced pressure. The redidue was purified by silica gel column chromatography (0-40% EtOAc/hexane) to afford the desired product as an-off-white solid (141 mg, 30% yield). 1H NMR (400 MHz, DMSO) δ 11.24 (s, 1H), 8.65 (s, 1H), 8.44 (d, J=1.6 Hz, 1H), 8.33 (d, J=5.7 Hz, 1H), 7.66-7.47 (m, 5H). LCMS (ESI) m/z: 472.7 [M+H+].

Fuente