Reacción #70526

Ecuación de reacción

6-(1H-Indol-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-amine

(3-methyl-1H-pyrazol-1-yl)acetic acid

HATU

DIPEA

HCl

(3-Methyl-1H-pyrazol-1-yl)acetic acid

HATU

DIPEA

→

title compound

Rendimiento 31.0%

N-[6-(1H-Indol-4-yl)-1H-indazol-4-yl]-2-(3-methyl-1H-pyrazol-1-yl)acetamide

Rendimiento 31.0%

Disolventes

DMF

MeOH

DMF

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGthe reaction was stirred for 5 h
2. 2
   workup.STIRRINGafter stirring together for 10 mins
3. 3
   workup.STIRRINGthe reaction was stirred for 2 days under a nitrogen atmosphere at RT
4. 4
   Lavadoeluted with DCM
5. 5
   Otroevaporated in vacuo
6. 6
   workup.STIRRINGstirred for ˜30 mins at RT
7. 7
   OtroThe solvent was evaporated in vacuo
8. 8
   workup.DISSOLUTIONthe residue was dissolved in MeOH
9. 9
   Otro1:1, v/v) and purified by Mass Directed Automated Preparative HPLC
10. 10
    OtroThe solvent was dried under a stream of nitrogen

Procedimiento

(3-Methyl-1H-pyrazol-1-yl)acetic acid (38 mg, 0.27 mmol) (from Art-Chem GmbH), HATU (126 mg, 0.33 mmol) and DIPEA (0.158 ml, 0.91 mmol) were dissolved in DMF (2 ml) and stirred under nitrogen for 30 mins. 6-(1H-Indol-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-amine (100 mg, 0.30 mmol) was added and the reaction was stirred for 5 h. Further (3-methyl-1H-pyrazol-1-yl)acetic acid (38 mg, 0.27 mmol), HATU (126 mg, 0.33 mmol) and DIPEA (0.158 ml, 0.91 mmol) in DMF (1 ml) was added, after stirring together for 10 mins, and the reaction was stirred for 2 days under a nitrogen atmosphere at RT. The reaction was loaded on to a PS-aminopropyl cartridge (10 g) and eluted with DCM. Appropriate fractions were combined and evaporated in vacuo. MeOH (2 ml) and 2 M HCl (aq) (45 μl, 0.09 mmol) were added and stirred for ˜30 mins at RT. The solvent was evaporated in vacuo and the residue was dissolved in MeOH:DMSO (2 ml; 1:1, v/v) and purified by Mass Directed Automated Preparative HPLC using method B. The solvent was dried under a stream of nitrogen to give title compound (31 mg).

Fuente