Reacción #67137

Ecuación de reacción

6-Bromo-1-methyl-1H-indazole-4-carboxylic acid

thionyl chloride

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

DIPEA

→

title compound

Rendimiento 60.7%

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

Rendimiento 60.7%

Disolventes

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe thionyl chloride was removed in vacuo
2. 2
   Otroexcess azeotroped with dry diethyl ether
3. 3
   Otroto give a yellow solid
4. 4
   TemperaturaThe reaction mixture was heated to 60° C. for 20 mins
5. 5
   OtroSolvent was removed in vacuo
6. 6
   Otrothe residue partitioned between dichloromethane (15 ml) and water (15 ml)
7. 7
   OtroThe layers were separated
8. 8
   Concentraciónthe organic phase concentrated in vacuo
9. 9
   Otroto give a green solid which
10. 10
    Otrowas purified by column chromatography, loading in dichloromethane
11. 11
    Otropurified on Flashmaster 11 silica (Si) 20 g
12. 12
    Otroover 30 mins
13. 13
    Otroevaporated in vacuo

Procedimiento

6-Bromo-1-methyl-1H-indazole-4-carboxylic acid (480 mg, 1.882 mmol) was suspended in thionyl chloride (4.12 ml, 56.5 mmol) and heated to 100° C. for 30 mins. The thionyl chloride was removed in vacuo and excess azeotroped with dry diethyl ether to give a yellow solid. This was dissolved in dry tetrahydrofuran (THF) (15 ml) and 2-[(2R,6S)-2,6-dimethyl-4-morpholinyl]acetohydrazide (529 mg, 2.82 mmol) and DIPEA (1.315 ml, 7.53 mmol) were added. The reaction mixture was heated to 60° C. for 20 mins. Solvent was removed in vacuo and the residue partitioned between dichloromethane (15 ml) and water (15 ml). The layers were separated and the organic phase concentrated in vacuo to give a green solid which was purified by column chromatography, loading in dichloromethane and purified on Flashmaster 11 silica (Si) 20 g using a 0-100% ethyl acetate-cyclohexane+0-20% MeOH over 30 mins. The appropriate fractions were combined and evaporated in vacuo to afford the title compound as a yellow solid (485 mg). LCMS (Method A) Rt 0.49 min, MH+ 424.

Fuente