Reacción #2292784

Ecuación de reacción

NaHCO3

(S)-tert-butyl 2-methylpiperazine-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 38.5%

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

Rendimiento 38.5%

Disolventes

1,4-dioxane

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaAfter cooling for 10 minutes
2. 2
   Extracciónextracted with EtOAc (3×)
3. 3
   Secadodried 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, 25-50% 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 250 mL round-bottom flask were added (S)-tert-butyl 2-methylpiperazine-1-carboxylate (3.94 g, 19.7 mmol) and (S)-1-(6-bromo-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine (2.5 g, 9.8 mmol) in 1,4-dioxane (23 mL). To the resulting solution was added potassium 2-methylpropan-2-olate (1 M in THF, 21 mL, 21 mmol), and the mixture was heated to 90° C. for 1 hour. After cooling for 10 minutes, the red mixture was poured into 300 mL of saturated NaHCO3 and then extracted with EtOAc (3×). The organic layers were combined, dried over MgSO4, filtered, and concentrated in vacuo to give crude product, which was purified by preparative HPLC (acid mode, 25-50% ACN/water gradient). The product-containing fractions were combined, concentrated in vacuo, and partitioned between saturated NaHCO3 and EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated to give the title compound (1.41 g, 38.4%). ESI-MS m/z [M+H]+ calc'd for C20H31N5O2, 374. found 374.

Fuente