Reacción #2292777

Ecuación de reacción

NaHCO3

potassium 2-methylpropan-2-olate

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

tert-butyl 1,4-diazepane-1-carboxylate

→

title compound

Rendimiento 34.0%

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

Rendimiento 34.0%

Disolventes

dioxane

EtOAc

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroAfter evacuating the flask
2. 2
   Otroflushing it with nitrogen
3. 3
   TemperaturaAfter cooling
4. 4
   SecadoThe combined organic layers were dried over MgSO4
5. 5
   Filtraciónfiltered
6. 6
   Concentraciónconcentrated in vacuo
7. 7
   OtroThe crude product was purified by preparative HPLC (acid mode, 25-50% ACN/water gradient)
8. 8
   Concentraciónconcentrated in vacuo
9. 9
   Otroto remove ACN
10. 10
    Extracciónextracted with EtOAc
11. 11
    Secadodried over MgSO4
12. 12
    Filtraciónfiltered
13. 13
    Concentraciónconcentrated in vacuo

Procedimiento

To a 50 mL pear flask were added (S)-1-(6-bromo-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine (153 mg, 0.602 mmol) and tert-butyl 1,4-diazepane-1-carboxylate (241 mg, 1.20 mmol). After evacuating the flask and flushing it with nitrogen, the flask was charged with dioxane (1.6 mL) and potassium 2-methylpropan-2-olate (1.0 M in THF) (1.32 mL, 1.32 mmol). The mixture was then heated to 90° C. for 1 hour. After cooling, the mixture was worked up with saturated NaHCO3 and EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified by preparative HPLC (acid mode, 25-50% ACN/water gradient). The product-containing fractions were combined, neutralized with saturated NaHCO3, concentrated in vacuo to remove ACN, and then extracted with EtOAc. The organic layers were combined, dried over MgSO4, filtered, and concentrated in vacuo to give the title compound (76 mg, 34%). ESI-MS m/z [M+H]+ calc'd for C20H31N5O2, 374. found 374.

Fuente