反应详情

A solution of 4-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}-3-hydroxybutanoic acid (50.0 mg, 0.11 mmol, prepared in analogy to Example 11-3), sodium borohydride (100.0 g, 2.6 mmol) and iodine (300.0 mg, 1.2 mmol) in tetrahydrofuran (10.0 mL) was stirred at room temperature for 16 hours. The reaction mixture was diluted with water (20 mL) and extracted with ethyl acetate (100 mL). The organic layer was washed with brine (50 mL×2), dried over anhydrous sodium sulfate and then concentrated in vacuo. The residue was purified by preparative HPLC to afford 20.0 mg of the desired product as a light yellow solid (yield was 41.2%). MS obsd. (ESI+) [(M+H)+] 442, 1H NMR (400 MHz, CD3OD) δ ppm 8.04 (d, J=7.58 Hz, 1 H), 7.90 (d, J=7.58 Hz, 1 H), 7.81 (brs, 1 H), 7.75-7.59 (m, 2 H), 7.59-7.41 (m, 2 H), 6.10 (s, 1 H), 5.25 (brs, 2 H), 4.53 (brs, 2 H), 4.12 (brs, 1 H), 3.82 (t, J=5.94 Hz, 2 H), 3.68 (brs, 2 H), 3.55 (dd, J=13.77, 4.17 Hz, 1 H), 3.44 (dd, J=13.64, 7.33 Hz, 1 H), 2.45 (s, 3 H), 1.97-1.73 (m, 2 H).

1. extractionextracted with ethyl acetate (100 mL)
2. washThe organic layer was washed with brine (50 mL×2)
3. dry with materialdried over anhydrous sodium sulfate
4. concentrationconcentrated in vacuo
5. customThe residue was purified by preparative HPLC