反应详情

To a solution of {4-[(1-Benzenesulfonyl-1H-benzoimidazol-2-ylmethyl)-(3-methyl-pyridin-2-ylmethyl)-amino]-butyl}-carbamic acid tert-butyl ester (0.202 g, 0.36 mmol) in CH2Cl2 (3 mL) was added TFA (2 mL) and the resultant solution was stirred at room temperature for 1 hour. The mixture was concentrated and the residue was portioned between CH2Cl2 (10 mL) and saturated Na2CO3 (5 mL). Solid Na2CO3 was added until the aqueous phase was basic (pH˜9) to litmus paper. The phases were separated and the aqueous phase was extracted with CH2Cl2 (3×10 mL). The combined organic extracts were dried (Na2SO4) and concentrated. Purification of the crude material by radial chromatography on silica gel (1 mm plate, 50:1:1 CH2Cl2-MeOH—NH4OH) provided 72 mg (42%) of COMPOUND 144 as a pale yellow oil. 1H NMR (CDCl3) δ 1.25-1.37 (m, 2H), 1.47-1.57 (m, 4H), 2.16 (s, 3H), 2.58 (t, 2H, J=7.2 Hz), 2.78 (t, 2H, J=7.5 Hz), 4.03 (s, 2H), 4.33 (s, 2H), 7.07 (dd, 1H, J=4.8, 7.5 Hz), 7.30-7.44 (m, 5H), 7.55-7.60 (m, 1H), 7.68-7.72 (m, 1H), 7.93-8.03 (m, 3H), 8.35 (d, 1H, J=4.2 Hz); 13C NMR (CDCl3) δ 18.78, 23.49, 31.79, 42.22, 52.27, 53.79, 57.83, 113.92, 120.73. 122.61, 125.01, 125.47, 127.66, 129.70, 133.28, 133.45, 134.77, 138.31, 138.69, 142.14, 146.48, 152.39, 157.18; ES-MS m/z 464 (M+H). Anal. Calcd. For C25H29N5O2S.0.7H2O: C, 63.06; H, 6.43; N, 14.71; S, 6.73. Found: C, 63.10; H, 6.48; N, 14.42; S, 6.52.

1. concentrationThe mixture was concentrated
2. additionSolid Na2CO3 was added until the aqueous phase
3. customThe phases were separated
4. extractionthe aqueous phase was extracted with CH2Cl2 (3×10 mL)
5. dry with materialThe combined organic extracts were dried (Na2SO4)
6. concentrationconcentrated
7. customPurification of the crude material by radial chromatography on silica gel (1 mm plate, 50:1:1 CH2Cl2-MeOH—NH4OH)