Reacción #67157

Ecuación de reacción

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

N-[2-(methyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinyl]methanesulfonamide

potassium phosphate tribasic

sodium hydroxide

→

title compound

Rendimiento 99.6%

N-(2-(Methyloxy)-5-{4-[5-(6-oxa-9-azaspiro[4.5]dec-9-ylmethyl)-1,3,4-oxadiazol-2-yl]-1H-indazol-6-yl}-3-pyridinyl)methanesulfonamide

Rendimiento 99.6%

Disolventes

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 protected compound was dissolved in 1,4-dioxane (1 ml)
7. 7
   OtroThe mixture was evaporated to dryness under a stream of nitrogen
8. 8
   OtroThe residue was partitioned between ethyl acetate (5 ml) and saturated ammonium chloride (2 ml)
9. 9
   Otroseparated with a hydrophilic frit
10. 10
    OtroThe solvent was removed under a stream of nitrogen
11. 11
    workup.DISSOLUTIONthe crude residue was dissolved in DMSO (1 ml)
12. 12
    Otropurified by Mass Directed Automated Preparative HPLC

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 (74 mg, 0.133 mmol) in 1,4 dioxane (2.5 ml) and water (1 ml) was added N-[2-(methyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinyl]methanesulfonamide (47.8 mg, 0.146 mmol), 1,1′-bis(diphenylphosphino)ferrocene palladium dichloride (19.39 mg, 0.027 mmol) and potassium phosphate tribasic (84 mg, 0.398 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 protected compound was dissolved in 1,4-dioxane (1 ml) and sodium hydroxide (1 ml, 2.000 mmol) and stirred at room temperature for 4 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 crude residue was dissolved in DMSO (1 ml) and purified by Mass Directed Automated Preparative HPLC. The appropriate fraction was blown down under a stream of nitrogen to give the title compound as a white solid (71.5 mg).

Fuente