反应详情

(S)-Pyrrolidine-2-carboxylic acid (3-trifluoromethoxy-phenyl)-amide TFA salt (59.3 mg, 0.153 mmol, prepared as described in Sheme D5 steps A and B), (1-carbamoyl-1H-indol-3-yl)-acetic acid (40 mg, 0.183 mmol, prepared as described in Scheme A8) and HBTU (86.9 mg, 0.229 mmol) were dissolved in CH2Cl2 (4 mL) under nitrogen, DIPEA (52.3 μl, 0.306 mmol) was added and the reaction mixture was stirred at RT for 5 h. After completion of the reaction aqueous 1N HCl and EtOAc were added, the layers were separated and the aqueous one back-extracted twice with EtOAc. The combined organic extracts were washed with an aqueous saturated solution of NaHCO3, dried over Na2SO4, filtered and concentrated. The crude residue was purified by preparative HPLC (Waters SunFire C18-ODB, 5 μm, 19×50 mm, 20% CH3CN/H2O 2.5 min, 20-100% CH3CN/H2O in 10 min, CH3CN/H2O containing 0.1% HCOOH flow: 20 mL/min) to give after extraction of the pure fractions the desired compound. MS (LC/MS): 475 [M+H]+, 497 [M+Na]+; tR (HPLC conditions a) 3.47 min. DMF can also be used instead of Dichloromethane.

1. customthe layers were separated
2. extractionthe aqueous one back-extracted twice with EtOAc
3. washThe combined organic extracts were washed with an aqueous saturated solution of NaHCO3
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. customThe crude residue was purified by preparative HPLC (Waters SunFire C18-ODB, 5 μm, 19×50 mm, 20% CH3CN/H2O 2.5 min, 20-100% CH3CN/H2O in 10 min, CH3CN/H2O containing 0.1% HCOOH flow: 20 mL/min)
8. customto give
9. extractionafter extraction of the pure fractions the desired compound
10. custom3.47 min