Réaction #67134

Équation de réaction

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

Rendement 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

Rendement 73.9%

Solvants

tetrahydrofuran

Conditions de réaction

Traitement

1. 1
   AutreThe solvent was removed in vacuo
2. 2
   Autrethe residue partitioned between dichloromethane (15 ml) and saturated sodium bicarbonate solution (15 ml)
3. 3
   AutreThe layers were separated (hydrophobic frit)
4. 4
   Lavagethe aqueous washed with further dichloromethane (5 ml)
5. 5
   Concentrationthe combined organics concentrated in vacuo
6. 6
   Autreto give a yellow solid
7. 7
   AutreThis was purified by column chromatography, loading in dichloromethane onto a silica cartridge 50 g
8. 8
   Autreover 40 mins
9. 9
   Autreevaporated in vacuo

Mode opératoire

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).

Source