반응 #333252

반응 방정식

diisopropylethylamine

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

HOBt

isopropylamine

HOBt

isopropylamine

→

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

수율 37.5%

용매

DMF

EDC

EDC

반응 조건

후처리

1. 1
   workup.STIRRINGThe reaction mixture was stirred at room temperature overnight
2. 2
   workup.STIRRINGThe reaction was stirred for 1 h
3. 3
   기타then quenched with water
4. 4
   추출extracted with EtOAc (2×)
5. 5
   세척The combined organic layers were washed with 10% citric acid
6. 6
   건조then dried over MgSO4
7. 7
   농축concentrated
8. 8
   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 (75 mg, 0.16 mmol), HOBt (63 mg, 0.38 mmol) and EDC (72 mg, 0.38 mmol) in DMF was added isopropylamine (84 ul, 0.98 mmol). The reaction mixture was stirred at room temperature for 1.5 h then additional HOBt, EDC, and isopropylamine were added. The reaction mixture was stirred at room temperature overnight then diisopropylethylamine (170 ul, 0.98 mmol) was added. The reaction was stirred for 1 h 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 30 mg (37%) of 2-(4,6-difluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide as a white solid.

출처