反应详情

温度

23 °C

General Procedure for mixed anhydride coupling—Isobutyl chloroformate (32 ml, 0.24 mmol) was added dropwise to a −20-30+ C. solution of 4-t-butoxycarbonyl aminobutyric acid (19) (50.1 mg, 0.247 mmol), 4-methyimorpholine (124 ml, 1.23 mmol), and THF (2 mL). After 20 min at −20-30° C., 6-Amino-3-(4-pyridyl)-2-(4-fluorophenyl)-7-aza-indole (17) (75 mg, 0.24 mmol) and THF (3 mL) was added in one portion. The reaction was allowed to warm to 23° C. After 16 h at 23° C., the reaction was poured into saturated bicarbonate (80 mL), extracted with ethyl acetate (2×100 mL), washed with brine (1×100 mL), and dried (Na2SO4). After concentration in vacuo, the residue was purified by application to two preparative chromatography plates (silica gel 2 mm thickness, 100% ethyl acetate) to afford 6-(4′-t-butoxycarbonylamino-1′-oxo-butylamino)-3-(4-pyridyl)-2-(4-fluorophenyl)-7-aza-indole (20) as a solid: Mass Spectrum (CI) 489 (MH+). Ethyl chloroformate can be used in place of isobutyl chloroformate in this process.

1. additionwas added dropwise to a −20-30+ C
2. waitAfter 16 h at 23° C.
3. extractionextracted with ethyl acetate (2×100 mL)
4. washwashed with brine (1×100 mL)
5. dry with materialdried (Na2SO4)
6. concentrationAfter concentration in vacuo
7. customthe residue was purified by application to two preparative chromatography plates (silica gel 2 mm thickness, 100% ethyl acetate)