Reacción #159178

Ecuación de reacción

DIPEA

2-Methoxycarbonylamino-3-methyl-butyric acid

HATU

2-[5-(5-Bromo-3a,6a-dihydro-thieno[3,2-b]thiophen-2-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HCl

→

title compound

Rendimiento 90.0%

(1-{2-[5-(5-Bromo-3a,6a-dihydro-thieno[3,2-b]thiophen-2-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester

Rendimiento 90.0%

Disolventes

EtOAc

DMF

DCM

Condiciones de reacción

Tratamiento posterior

1. 1
   Concentraciónthe reaction mixture was concentrated
2. 2
   OtroThe solid was dried
3. 3
   OtroThe stirred reaction mixture
4. 4
   workup.WAITAfter 50 min
5. 5
   Temperaturait was warmed to RT
6. 6
   LavadoThe organic phase was washed with saturated aqueous NaHCO3 and brine
7. 7
   Secadobefore being dried over MgSO4
8. 8
   Filtraciónfiltered
9. 9
   Concentraciónconcentrated
10. 10
    OtroThe crude residue was purified by silica column chromatography

Procedimiento

2-[5-(5-Bromo-3a,6a-dihydro-thieno[3,2-b]thiophen-2-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (250 mg, 0.548 mmol) was dissolved in DCM (4 mL) and treated with HCl (4 M in dioxane, 1 mL, 4 mmol). After stirring for 1.5 h, the reaction mixture was concentrated. The solid was dried, then combined with 2-Methoxycarbonylamino-3-methyl-butyric acid (106 mg, 0.603 mmol), HATU (229 mg, 0.603 mmol) and DMF (6 mL). The stirred reaction mixture was cooled to 0° C. and DIPEA (0.48 mL, 2.74 mmol) was added dropwise. After 50 min, it was warmed to RT. 12 min later, the reaction mixture was diluted with EtOAc. The organic phase was washed with saturated aqueous NaHCO3 and brine before being dried over MgSO4, filtered and concentrated. The crude residue was purified by silica column chromatography to afford the title compound (252 mg, 90%).

Fuente