反应详情

To a solution of 3-(morpholin-4-sulfonyl)-2(R)-[2,2,2-trifluoro-1(S)-(4-fluorophenyl)-ethylamino]-propionic acid (0.034 g, 0.082 mmol) and the HCl salt of 1-aminocyclopropane-carbonitrile (OmegaChem, 0.013 g, 0.107 mmol) in DMF (1 mL) at rt was added solid HATU (PacificChem, 0.041 g, 0.107 mmol) in one portion followed by DIPEA (Aldrich, 0.043 mL, 0.246 mmol) to produce a bright yellow, clear solution. After stirring at rt for 1 h, the reaction was diluted in EtOAc and quenched with 10% aqueous NaHCO3. Water was added to dissolve precipitated solids. The aqueous layer was separated and extracted with EtOAc. The combined organics were washed with brine and dried over anhydrous Na2SO4. Following concentration in vacuo, the crude product was purified by column chromatography on SiO2 (2/1 EtOAc/Hex). Following concentration in vacuo, 0.020 g (51%) of N-(1-cyanocyclopropyl)-3-(morpholin-4-sulfonyl)-2(R)-[2,2,2-trifluoro-1(S)-(4-fluorophenyl)ethylamino]propionamide was obtained as a white foamy solid with repeated concentration from CH2Cl2. LC/MS: 501.4 (M+Na)+; 479.3 (M+H)+; 477.2 (M−H)−.

1. customto produce a bright yellow, clear solution
2. customquenched with 10% aqueous NaHCO3
3. additionWater was added
4. dissolutionto dissolve
5. customprecipitated solids
6. customThe aqueous layer was separated
7. extractionextracted with EtOAc
8. washThe combined organics were washed with brine
9. dry with materialdried over anhydrous Na2SO4
10. concentrationconcentration in vacuo
11. customthe crude product was purified by column chromatography on SiO2 (2/1 EtOAc/Hex)
12. concentrationconcentration in vacuo