Reacción #67162

Ecuación de reacción

sodium hydroxide

9-({5-[6-bromo-1-(phenylsulfonyl)-1H-indazol-4-yl]-1,3,4-oxadiazol-2-yl}methyl)-6-oxa-9-azaspiro[4.5]decane

4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole

potassium phosphate tribasic

→

title compound

Rendimiento 25.8%

9-({5-[6-(1H-Indol-4-yl)-1H-indazol-4-yl]-1,3,4-oxadiazol-2-yl}methyl)-6-oxa-9-azaspiro[4.5]decane

Rendimiento 25.8%

Disolventes

1,4-dioxane

1,4 dioxane

water

Condiciones de reacción

Tratamiento posterior

1. 1
   Lavadowashing with MeOH
2. 2
   OtroThe solvent was removed under a stream of nitrogen
3. 3
   Otrothe residue was partitioned between DCM (10 ml) and water (10 ml)
4. 4
   Otroseparated with a hydrophobic frit
5. 5
   Otrothe solvent again removed under a stream of nitrogen
6. 6
   workup.DISSOLUTIONThe residue was dissolved in DMSO (2 ml)
7. 7
   Otropurified by Mass Directed Automated Preparative HPLC
8. 8
   Otroto give a yellow solid
9. 9
   OtroThe mixture was evaporated to dryness under a stream of nitrogen
10. 10
    OtroThe residue was partitioned between ethyl acetate (5 ml) and saturated ammonium chloride (2 ml)
11. 11
    Otroseparated with a hydrophilic frit
12. 12
    OtroThe solvent was removed under a stream of nitrogen
13. 13
    Secadodried from 1,4-dioxane/water (1:1, 2 ml) overnight

Procedimiento

To a solution of 9-({5-[6-bromo-1-(phenylsulfonyl)-1H-indazol-4-yl]-1,3,4-oxadiazol-2-yl}methyl)-6-oxa-9-azaspiro[4.5]decane (100 mg, 0.179 mmol) in 1,4 dioxane (2.5 ml) and water (0.25 ml) was added 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (56.6 mg, 0.233 mmol, available from Frontier Scientific Europe), 1,1′-bis(diphenylphosphino)ferrocene palladium dichloride (26.2 mg, 0.036 mmol) and potassium phosphate tribasic (114 mg, 0.537 mmol). The mixture was heated under microwave irradiation at 100° C. for 20 mins. The mixture was passed through a 1 g silica SPE cartridge, washing with MeOH. The solvent was removed under a stream of nitrogen and the residue was partitioned between DCM (10 ml) and water (10 ml), separated with a hydrophobic frit and the solvent again removed under a stream of nitrogen. The residue was dissolved in DMSO (2 ml) and purified by Mass Directed Automated Preparative HPLC. The appropriate fractions were blown down under a stream of nitrogen to give a yellow solid. The solid was dissolved in 1,4-dioxane (1 ml) and sodium hydroxide (1 ml, 2.000 mmol) and stirred at room temperature for 3 h. The mixture was evaporated to dryness under a stream of nitrogen. The residue was partitioned between ethyl acetate (5 ml) and saturated ammonium chloride (2 ml) and separated with a hydrophilic frit. The solvent was removed under a stream of nitrogen and the residue was freeze dried from 1,4-dioxane/water (1:1, 2 ml) overnight to give the title compound as a cream solid (21 mg).

Fuente