Reacción #67133

Ecuación de reacción

6-Bromo-1-[(4-methylphenyl)sulfonyl]-1H-indazole-4-carboxylic acid

thionyl chloride

2-[(2R,6S)-2,6-dimethyl-4-morpholinyl]acetohydrazide

DIPEA

→

title compound

Rendimiento 44.3%

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

Rendimiento 44.3%

Disolventes

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe thionyl chloride was removed in vacuo and excess aziotroped with dry diethyl ether
2. 2
   Otroto give a yellow solid
3. 3
   TemperaturaThe reaction mixture was heated to 60° C. for 20 mins
4. 4
   OtroThe solvent was removed in vacuo
5. 5
   Otrothe residue partitioned between dichloromethane (50 ml) and water (50 ml)
6. 6
   OtroThe layers were separated
7. 7
   Concentraciónthe organic concentrated in vacuo
8. 8
   Otroto give a yellow foam
9. 9
   OtroThis was purified by column chromatography, loading in dichloromethane onto a silica cartridge (50 g)
10. 10
    Lavadoeluting with 0-100% ethyl acetate-cyclohexane over 30 mins
11. 11
    Otroevaporated in vacuo

Procedimiento

6-Bromo-1-[(4-methylphenyl)sulfonyl]-1H-indazole-4-carboxylic acid (1.5 g, 3.80 mmol) was suspended in thionyl chloride (8.31 ml, 114 mmol) and heated to 100° C. for 30 mins. The thionyl chloride was removed in vacuo and excess aziotroped with dry diethyl ether to give a yellow solid. This was dissolved in dry tetrahydrofuran (40 ml) and 2-[(2R,6S)-2,6-dimethyl-4-morpholinyl]acetohydrazide (1.066 g, 5.69 mmol) and DIPEA (2.65 ml, 15.18 mmol) added. The reaction mixture was heated to 60° C. for 20 mins. The solvent was removed in vacuo and the residue partitioned between dichloromethane (50 ml) and water (50 ml). The layers were separated and the organic concentrated in vacuo to give a yellow foam. This was purified by column chromatography, loading in dichloromethane onto a silica cartridge (50 g), eluting with 0-100% ethyl acetate-cyclohexane over 30 mins. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a yellow solid (950 mg).

Fuente