Diisopropylethylamine → 2-(6-Fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-2-cyano-2-methyl-ethyl)-amide

(R)-3-Amino-2-methyl-propionitrile trifluoroacetate (crude from Step 3) was dissolved in acetonitrile (2.8 ml) to which was then added 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (80 mg, 0.18 mmol), O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (70 mg, 0.22 mmol) and N,N-diisopropylethylamine (0.11 ml, 0.63 mmol). The reaction was stirred at room temperature for 18 h. Additional O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (50 mg, 0.16 mmol) and N,N-diisopropylethylamine (0.11 ml, 0.63 mmol) were added and stirring was continued for 24 h. Water and ethyl acetate were added. The layers were separated and the aqueous layer was extracted twice with ethyl acetate. The combined organic layers were washed with sodium chloride solution and dried over sodium sulfate. After evaporation, the residue was purified by silica gel chromatography (methanol/dichloromethane) to afford 33 mg (36%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-2-cyano-2-methyl-ethyl)-amide. (M+Na)+=530.

1. stirringstirring
2. waitwas continued for 24 h
3. customThe layers were separated
4. extractionthe aqueous layer was extracted twice with ethyl acetate
5. washThe combined organic layers were washed with sodium chloride solution
6. dry with materialdried over sodium sulfate
7. customAfter evaporation
8. customthe residue was purified by silica gel chromatography (methanol/dichloromethane)

ORDレコード

ord-526a2114f66847ee97e953a6145bde36

出典データセット

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08658646B2