反应详情

温度

90 °C

(4-{[(3,5-Dimethyl-pyridin-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-3-hydroxymethyl-benzylamino)-acetic acid methyl ester (0.140 g, 0.29 mmol) was dissolved in a mixture of EtOH (3 mL) and 3M NaOH (7 mL). The colorless mixture was stirred at 90° C. for 16 hours to give an orange/brown solution. 3M HCl was added until pH 2 followed by the addition of 3M NaOH until the pH 9 and a white precipitate formed. The white solid was removed via suction filtration and the filtrate was extracted with 95:5 (CHCl3/MeOH) (9×30 mL) and the combined organic extracts were dried (Na2SO4), filtered and concentrated under reduced pressure. Purification by column chromatography on silica gel (MeCN:MeOH:NH4OH, 6:3:1, v/v/v) afforded (4-{[(3,5-dimethyl-pyridin-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-3-hydroxymethyl-benzylamino)-acetic acid (0.106 g, 78%) as a pale yellow solid. 1H NMR (CD3OD) δ 1.58 (m, 1H), 2.05 (m, 2H), 2.17 (s+m, 4H), 2.27 (s, 3H), 2.65 (m, 1H), 2.83 (m, 1H), 3.43 (s, 2H), 3.74 (m, 4H), 4.16-4.22 (m, 4H), 4.39 (d, 1H, J=11.1 Hz), 7.11 (m, 1H), 7.25-7.42 (m, 5H), 8.10 (s, 1H), 8.28 (s, 1H). 13C NMR (CD3OD) δ 18.2, 18.9, 22.4, 23.2, 30.5, 52.0, 55.0, 55.1, 59.8, 63.2, 123.4, 130.5, 131.1, 133.1, 133.6, 133.8, 134.7, 135.8, 136.9, 138.7, 140.1, 141.3, 143.7, 146.9, 147.8, 154.5, 158.0, 171.5. HPLC: 97%. ES-MS m/z 475 [M+H]+. Anal. Calcd. for C28H34N4O31.3 H2O: C, 67.53; H, 7.41; N, 11.25. Found: C, 67.65; H, 7.36; N, 11.09.

1. customto give an orange/brown solution
2. customa white precipitate formed
3. customThe white solid was removed via suction filtration
4. extractionthe filtrate was extracted with 95:5 (CHCl3/MeOH) (9×30 mL)
5. dry with materialthe combined organic extracts were dried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customPurification by column chromatography on silica gel (MeCN:MeOH:NH4OH, 6:3:1, v/v/v)