反应详情

A solution of the product from Example 104A (0.065 g, 0.119 mmoles), glycine methyl ester hydrochloride (0.0300 g, 0.24 mmoles), and diisopropylethylamine (0.042 mL, 0.24 mmoles) in DMF (0.3 mL) was treated with EDAC (0.032 g, 0.167 mmoles) and HOBT (0.0225 g, 0.167 mmoles). The resulting mixture was shaken for 12 h. The crude products were diluted with diethyl ether, extracted with sat. NH4Cl, extracted with H2O (2×), rinsed with brine, dried (Na2SO4), and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel. The product was dissolved in EtOH (0.5 mL) and THF (0.5 mL) and treated with 2N NaOH (1.0 mL) for 4 h. The resulting mixture was poured into 3N HCl and extracted with ethyl acetate (2×). The combined organics were rinsed with brine, dried (Na2SO4), and concentrated under reduced pressure. Purification by preparative HPLC (CH3CN:0.1% trifluoroacetic acid in H2O) on a YMC ODS Guardpak column yielded the title compound (0.0625 g, 87%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ8.97 (s, 1 H), 8.18 (t, 1 H), 7.23 (m, 9 H), 7.00 (m, 3 H), 6.86 (m, 4 H), 4.05 (s, 2 H), 4.01 (s, 2 H), 3.73 (d, 2 H), 2.91 (s, 3 H), 2.79 (t, 2 H), 2.40 (m, 3 H), 2.39 (s, 3 H); MS (APCI) m/z 602 (M+H+).

1. extractionextracted with sat. NH4Cl
2. extractionextracted with H2O (2×)
3. washrinsed with brine
4. dry with materialdried (Na2SO4)
5. concentrationconcentrated under reduced pressure
6. customThe residue was purified by flash chromatography on silica gel
7. dissolutionThe product was dissolved in EtOH (0.5 mL)
8. additionTHF (0.5 mL) and treated with 2N NaOH (1.0 mL) for 4 h
9. additionThe resulting mixture was poured into 3N HCl
10. extractionextracted with ethyl acetate (2×)
11. washThe combined organics were rinsed with brine
12. dry with materialdried (Na2SO4)
13. concentrationconcentrated under reduced pressure
14. customPurification by preparative HPLC (CH3CN:0.1% trifluoroacetic acid in H2O) on a YMC ODS Guardpak column