反应详情

温度

25 °C

In an oven-dried 5-mL round bottom flask purged with nitrogen, dissolved the product of Example 108B (70 mg, 0.142 mmol) and (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (26.2 mg, 0.150 mmol) in anhydrous DMSO (1.5 mL), added HATU (58.6 mg, 0.150 mmol) and diisopropylethylamine (0.050 mL, 0.285 mmol), and stirred dark yellow solution at 25° C. for 15 min. Diluted the reaction with MeOH (1.5 mL) and purified by RP-C18 HPLC (Waters Prep LC, 40 mm Module with Nova Pak HR C18 6 μm 40×100 mm Prep Pak cartridge) eluting with a 30 min gradient of 95:5 0.1% TFA in H2O/AcCN to 25:75 0.1% TFA in H2O/AcCN, then 10 min to 100% AcCN at 20 mL/min. Pure fractions were concentrated by rotary evaporation (water bath 35°) to a small volume, partitioned between 20% iPrOH/CHCl3 (50 mL), and sat'd aq NaHCO3 (15 mL), separated layers, dried organic extract over anhydrous MgSO4, filtered, and concentrated by rotary evaporation to afford the title compound as a light yellow solid (48 mg, 52%). 1H NMR showed the material to be ˜3:1 trans:cis mixture; MS (ESI+) m/z 649 (M+H)+, 1297 (2M+H)+.

1. customIn an oven-dried 5-mL round bottom flask purged with nitrogen
2. additionDiluted
3. custompurified by RP-C18 HPLC (Waters Prep LC, 40 mm Module with Nova Pak HR C18 6 μm 40×100 mm Prep Pak cartridge)
4. washeluting with a 30 min gradient of 95:5 0.1% TFA in H2O/AcCN to 25:75 0.1% TFA in H2O/AcCN
5. concentrationPure fractions were concentrated by rotary evaporation (water bath 35°) to a small volume
6. custompartitioned between 20% iPrOH/CHCl3 (50 mL)
7. customseparated layers
8. extractiondried organic extract over anhydrous MgSO4
9. filtrationfiltered
10. concentrationconcentrated by rotary evaporation