반응 #333258

반응 방정식

2-(4,6-difluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

HOBt

EDC

isopropylamine

N,N-diisopropylethylamine

DMF

→

2-(6-fluoro-1-oxetan-3-yl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide

수율 78.0%

반응 조건

후처리

1. 1
   기타then quenched with water
2. 2
   추출extracted with EtOAc (2×)
3. 3
   세척The combined organic layers were washed with 10% citric acid
4. 4
   건조then dried over MgSO4
5. 5
   농축concentrated
6. 6
   기타The residue was chromatographed over silica gel with 20% to 100% EtOAc/heptane

실험 절차

To a solution of 2-(4,6-difluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (115 mg, 0.23 mmol), HOBt (92 mg, 0.55 mmol) and EDC (105 mg, 0.55 mmol) in DMF (3 ml) was added isopropylamine (41 ul, 0.48 mmol) and N,N-diisopropylethylamine (0.17 ml, 0.95 mmol). The reaction mixture was stirred at room temperature overnight then quenched with water and extracted with EtOAc (2×). The combined organic layers were washed with 10% citric acid, sat NaHCO3, sat LiCl, and brine then dried over MgSO4 and concentrated. The residue was chromatographed over silica gel with 20% to 100% EtOAc/heptane to afford 98 mg (78%) of 2-(6-fluoro-1-oxetan-3-yl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide as a white solid.

출처