Reacción #67134

Ecuación de reacción

triethylammonium hydroxide

6-Bromo-N′-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]acetyl}-1-[(4-methylphenyl)sulfonyl]-1H-indazole-4-carbohydrazide

phosphorus pentoxide

6-bromo-N′-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]acetyl}-1-[(4-methylphenyl)sulfonyl]-1H-indazole-4-carbohydrazide

→

title compound

Rendimiento 73.9%

6-Bromo-4-(5-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3,4-oxadiazol-2-yl)-1-[(4-methylphenyl)sulfonyl]-1H-indazole

Rendimiento 73.9%

Disolventes

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe solvent was removed in vacuo
2. 2
   Otrothe residue partitioned between dichloromethane (15 ml) and saturated sodium bicarbonate solution (15 ml)
3. 3
   OtroThe layers were separated (hydrophobic frit)
4. 4
   Lavadothe aqueous washed with further dichloromethane (5 ml)
5. 5
   Concentraciónthe combined organics concentrated in vacuo
6. 6
   Otroto give a yellow solid
7. 7
   OtroThis was purified by column chromatography, loading in dichloromethane onto a silica cartridge 50 g
8. 8
   Otroover 40 mins
9. 9
   Otroevaporated in vacuo

Procedimiento

6-Bromo-N′-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]acetyl}-1-[(4-methylphenyl)sulfonyl]-1H-indazole-4-carbohydrazide (950 mg, 1.683 mmol) was dried over phosphorus pentoxide in a desicator overnight. 6-bromo-N′-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]acetyl}-1-[(4-methylphenyl)sulfonyl]-1H-indazole-4-carbohydrazide (950 mg, 1.683 mmol) and methoxycarbonylsulfamoyl)triethylammonium hydroxide (602 mg, 2.52 mmol) were suspended in anhydrous tetrahydrofuran (20 ml) and heated to 75° C. for 2 h. The solvent was removed in vacuo and the residue partitioned between dichloromethane (15 ml) and saturated sodium bicarbonate solution (15 ml). The layers were separated (hydrophobic frit), the aqueous washed with further dichloromethane (5 ml) and the combined organics concentrated in vacuo to give a yellow solid. This was purified by column chromatography, loading in dichloromethane onto a silica cartridge 50 g, using a 0-100% ethyl acetate-cyclohexane over 40 mins. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a white solid (680 mg).

Fuente