Reacción #2292789

Ecuación de reacción

NaHCO3

(R)-tert-butyl 2-methylpiperazine-1-carboxylate

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

K2CO3

Potassium 2-methylpropan-2-olate

→

title compound

Rendimiento 33.0%

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

Rendimiento 33.0%

Disolventes

1,4-dioxane

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaAfter cooling for 10 minutes
2. 2
   ExtracciónThe mixture was extracted 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 (basic mode, 30-55% ACN/water gradient)
8. 8
   Concentraciónconcentrated in vacuo
9. 9
   Otropartitioned between saturated NaHCO3 and EtOAc
10. 10
    SecadoThe organic phase was dried over MgSO4
11. 11
    Filtraciónfiltered
12. 12
    Concentraciónconcentrated

Procedimiento

To a 50 mL pear flask were added (R)-tert-butyl 2-methylpiperazine-1-carboxylate (156 mg, 0.777 mmol) and (S)-1-(6-bromo-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine (94 mg, 0.370 mmol) in 1,4-dioxane (0.92 mL). Potassium 2-methylpropan-2-olate (1 M in THF, 0.81 mL, 0.81 mmol) was added, and the mixture was heated to 90° C. for 45 minutes. After cooling for 10 minutes, the red mixture was poured into saturated NaHCO3 and the pH was adjusted to ˜10 by adding K2CO3. The mixture was 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 (basic mode, 30-55% ACN/water gradient). The product-containing fractions were combined, concentrated in vacuo, and then partitioned between saturated NaHCO3 and EtOAc. The organic phase was dried over MgSO4, filtered, and concentrated to give the title compound as a colorless oil (45 mg, 33%). ESI-MS m/z [M+H]+ calc'd for C20H31N5O2, 374. found 374.

Fuente