반응 #70526

반응 방정식

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

수율 31.0%

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

수율 31.0%

용매

DMF

MeOH

DMF

반응 조건

후처리

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
   세척eluted with DCM
5. 5
   기타evaporated in vacuo
6. 6
   workup.STIRRINGstirred for ˜30 mins at RT
7. 7
   기타The solvent was evaporated in vacuo
8. 8
   workup.DISSOLUTIONthe residue was dissolved in MeOH
9. 9
   기타1:1, v/v) and purified by Mass Directed Automated Preparative HPLC
10. 10
    기타The solvent was dried under a stream of nitrogen

실험 절차

(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).

출처