Reacción #2292775

Ecuación de reacción

NaHCO3

tert-butyl piperazine-1-carboxylate

(S)-1-(6-bromo-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine

potassium 2-methylpropan-2-olate

→

title compound

Rendimiento 40.0%

tert-Butyl (S)-4-(5-(1-aminoethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)piperazine-1-carboxylate

Rendimiento 40.0%

Disolventes

1,4-dioxane

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaAfter cooling for 10 minutes
2. 2
   Extracciónextracted with EtOAc (3×)
3. 3
   SecadoThe combined organic layers were dried over MgSO4
4. 4
   Filtraciónfiltered
5. 5
   Concentraciónconcentrated in vacuo
6. 6
   Otroto give crude product, which
7. 7
   Otrowas purified by preparative HPLC (acid mode, 25-65% ACN/water gradient)
8. 8
   Concentraciónconcentrated in vacuo
9. 9
   Otropartitioned between saturated NaHCO3 and EtOAc
10. 10
    SecadoThe combined organic layers were dried over MgSO4
11. 11
    Filtraciónfiltered
12. 12
    Concentraciónconcentrated

Procedimiento

To a 50 mL pear flask were added tert-butyl piperazine-1-carboxylate (2.44 g, 12.7 mmol) and (S)-1-(6-bromo-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine (1.54 g, 6.06 mmol) in 1,4-dioxane (15 mL). To this solution was added potassium 2-methylpropan-2-olate (1 M in THF) (13.3 mL, 13.3 mmol), and the resulting mixture was heated to 90° C. for 45 minutes. After cooling for 10 minutes, the red mixture was poured into saturated NaHCO3 (300 mL) and then extracted with EtOAc (3×). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo to give crude product, which was purified by preparative HPLC (acid mode, 25-65% ACN/water gradient). The product-containing fractions were combined, concentrated in vacuo, and then partitioned between saturated NaHCO3 and EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated to give the title compound (872 mg, 40.0%). ESI-MS m/z [M+H]+ calc'd for C19H29N5O2, 360. found 360.

Fuente