Reacción #53717

Ecuación de reacción

N-tert-butoxycarbonylindole-2-boronic acid

sodium hydrogencarbonate

tert-butyl 3-iodo-5-(N-tert-butoxycarbonyl-2-trifluoromethoxybenzenesulfonylamino)indazolecarboxylate

→

N-[3-(1H-indol-2-yl)-1H-indazol-5-yl]-2-trifluoromethoxy-benzenesulfonamide

Rendimiento 58.3%

Disolventes

dimethylformamide

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaAfter cooling to a temperature in the region of 20° C.
2. 2
   Filtraciónthe catalyst is filtered through sintered glass with Celite® 535
3. 3
   Concentraciónthe filtrate is concentrated to dryness under reduced pressure in a rotary evaporator
4. 4
   OtroThe reaction crude
5. 5
   Otrois purified by preparative HPLC chromatography
6. 6
   workup.ADDITIONThe fractions containing the expected product
7. 7
   Concentraciónconcentrated
8. 8
   Lavadowashed with 10 ml of a saturated sodium hydrogencarbonate solution
9. 9
   SecadoThe organic phase is dried over magnesium sulfate
10. 10
    Filtraciónfiltered
11. 11
    Concentraciónconcentrated to dryness under reduced pressure

Procedimiento

N-[3-(1H-Indol-2-yl)-1H-indazol-5-yl]-2-trifluoromethoxybenzenesulfonamide can be obtained in the following way: 213.3 mg N-tert-butoxycarbonylindole-2-boronic acid in dimer form and 243 μl of a saturated sodium hydrogencarbonate solution and then 63.4 mg of tetrakis(triphenylphosphine)palladium[0] are added to a solution of 150 mg of tert-butyl 3-iodo-5-(N-tert-butoxycarbonyl-2-trifluoromethoxybenzenesulfonylamino)indazolecarboxylate in 4.5 ml of dimethylformamide. The suspension is heated in the region of 120° C. for 18 hours. After cooling to a temperature in the region of 20° C., the catalyst is filtered through sintered glass with Celite® 535, and the filtrate is concentrated to dryness under reduced pressure in a rotary evaporator. The reaction crude is purified by preparative HPLC chromatography coupled to a mass detector (LC/MS, conditions A). The fractions containing the expected product are pooled and concentrated, and then the base is released from the trifluoroacetate salt by being taken up in 10 ml of dichloromethane and washed with 10 ml of a saturated sodium hydrogencarbonate solution. The organic phase is dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure. 60.5 mg of N-[3-(1H-indol-2-yl)-1H-indazol-5-yl]-2-trifluoromethoxy-benzenesulfonamide are thus obtained in the form of a white solid melting at 172-174° C. (analytical LC/MS analysis: Tr=3.73 minutes; [M+H]+=473.07).

Fuente