|
With N-ethyl-N,N-diisopropylamine; HATU; In dichloromethane; at 20℃; |
Example 28 Synthesis of Compound 28 (S)-9-fluorenylmethyl 10-(2,2-diphenylethyl)-2,2-dimethyl-18-phenyl-4,9,13,16-tetraoxo-3,17-dioxa-5,10,15-triazaoctadecan-8-ylcarbamate To 2,2-diphenylethylamine (0.95 g, 7.4 mmol) in DCM (10 mL) was added the alpha,beta-unsaturated ketone 27 (5.7 mmol) in DCM (75 mL). After stirring at room temperature for 15 mins, Fmoc-L-2,4-diaminobutyric acid(Boc)-OH (2.4 g, 8.55 mmol) and DIC (0.87 mL, 5.6 mmol) were added. The reaction was stirred at room temperature overnight. The DCM was removed by rotary evaporation and the residue was subjected to column chromatography on silica gel using petroleum ether:EtOAc (1:1 to 0:1) to give 28 (1.5 g, 31percent) Alternatively, to 2,2-diphenylethylamine (0.97 g, 7.4 mmol) in DCM (20 mL) was added the alpha,beta-unsaturated ketone 27 (5.95 mmol) in DCM (40mL). After stirring at room temperature for 15 mins, Fmoc-L-2,4-diaminobutyric acid(Boc)-OH (2.4 g, 8.55 mmol), DIPEA (2.5 mL) and HATU (2.3 g, 6.0 mmol) were added. The reaction was stirred at room temperature overnight. The DCM was removed by rotary evaporation and the residue was taken up in EtOAc (100 mL). The organic layer was washed with saturated sodium bicarbonate solution (2*100 mL), saturated ammonium chloride solution (2*100 mL) and brine (2*100 mL). The organic phase was dried and the solvent removed under reduced pressure. The residue was subjected to column chromatography on silica gel using petroleum ether:EtOAc (3:1 to 1:1 to 0:1) to give 28 (0.86 g, 17percent). |
|
With diisopropyl-carbodiimide; In dichloromethane; at 20℃; |
Example 28 Synthesis of Compound 28 (S)-9-fluorenylmethyl 10-(2,2-diphenylethyl)-2,2-dimethyl-18-phenyl-4,9,13,16-tetraoxo-3,17-dioxa-5,10,15-triazaoctadecan-8-ylcarbamate To 2,2-diphenylethylamine (0.95 g, 7.4 mmol) in DCM (10 mL) was added the alpha,beta-unsaturated ketone 27 (5.7 mmol) in DCM (75 mL). After stirring at room temperature for 15 mins, Fmoc-L-2,4-diaminobutyric acid(Boc)-OH (2.4 g, 8.55 mmol) and DIC (0.87 mL, 5.6 mmol) were added. The reaction was stirred at room temperature overnight. The DCM was removed by rotary evaporation and the residue was subjected to column chromatography on silica gel using petroleum ether:EtOAc (1:1 to 0:1) to give 28 (1.5 g, 31percent) |