Réaction #67133

Équation de réaction

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

Rendement 44.3%

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

Rendement 44.3%

Solvants

tetrahydrofuran

Conditions de réaction

Traitement

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

Mode opératoire

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).

Source