Reacción #1462533

Ecuación de reacción

1-[2-oxo-2-(2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)ethyl]-5-phenyl-1H-1,5-benzodiazepine-2,4(3H,5H)-dione

tert-butyl 3-(bromomethyl)-1H-indazole-1-carboxylate

→

tert-butyl 3-({2,4-dioxo-1-[2-oxo-2-(2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)ethyl]-5-phenyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-3-yl}methyl)-1H-indazole-1-carboxylate

Disolventes

DMF

toluene

DMF

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGThe resulting solution was stirred 2 h at RT
2. 2
   Otroquenched with 5 mL of H2O
3. 3
   workup.ADDITIONThe reaction mixture was then poured into 50 mL of EtOAc
4. 4
   Extracciónextracted with H2O (2×50 mL)
5. 5
   OtroThe organic layer was separated
6. 6
   Secadodried (MgSO4)
7. 7
   Otrothe solvents removed in vacuo
8. 8
   OtroThe resultant material was purified by silica gel flash column chromatography

Procedimiento

To a stirring solution of 1-[2-oxo-2-(2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)ethyl]-5-phenyl-1H-1,5-benzodiazepine-2,4(3H,5H)-dione (1.0 g, 2.28 mM) in 15 mL DMF at 0° C. was added 1.1 equiv. of 0.5 M solution of KN(TMS)2 in toluene. The resulting solution was stirred 10–30 min, then a solution of tert-butyl 3-(bromomethyl)-1H-indazole-1-carboxylate (0.78 g, 2.5 mM) in 3 mL DMF was added. The resulting solution was stirred 2 h at RT and then quenched with 5 mL of H2O. The reaction mixture was then poured into 50 mL of EtOAc and extracted with H2O (2×50 mL). The organic layer was separated, dried (MgSO4), and the solvents removed in vacuo. The resultant material was purified by silica gel flash column chromatography using hexanes/EtOAc 1/1 providing 1.4 g of white solid.

Fuente