Acetic Acid → N-{4-[4-({(2S)-2-Hydroxy-3-[(2-oxo-2,3-dihydro-1H-benzimidazol-4-yl)oxy]propyl}-amino)-1-piperidineyl]phenyl}-5-(2-pyridinyl)-2-thiophenesulfonamide

Participants

Reaction Steps

5-Pyridin-2-yl-thiophene-2-sulfonic acid [4-(4-oxo-piperidine-1-yl)-phenyl]-amide (which was obtained in Example 227) (0.21 g, 0.5 mmol) and (S)-4-[2-hydroxy-3-aminopropoxy]-1,3-dihydro-2H-benzimidazol-2-one (U.S. Pat. No. 5,786,356/1998) (0.11 g, 0.5 mmol) were mixed in dimethylformamide (10 mL) and then treated with sodium triacetoxyborohydride (0.16 g, 0.75 mmol) and acetic acid (0.045 g, 0.75 mmol). After stirring at room temperature under a nitrogen atmosphere for one day the mixture was quenched with 1N NaOH and then poured into a saturated aqueous NaHCO3. The precipitate which formed was collected and purified by preparative thin layer chromatography (16% MeOH/CH2CH2) to give the titled compound as a pale yellowish solid; 1H NMR (300 MHz, DMSO-d6) δ 1.25-1.40 (m, 2H), 1.80-1.90 (m, 2H), 2.50-2.90 (m, 5H), 3.53 (brd, J=9.0 Hz, 2H), 3.85-4.00 (m, 2H), 4.00-4.10 (m, 1H), 4.91 (brs, 1H), 6.56 (d, J=5.7 Hz, 1H), 6.61 (d, J=5.7 Hz, 1H), 6.80-6.90 (m, 3H), 6.96 (d, J=6.6Hz, 2H), 7.36 (dd, J=3.3, 1.2Hz, 1H), 7.41 (d, J=3.0Hz, 1H), 7.75 (d, J=3.0 Hz, 1H), 7.88 (dd, J=6.0, 1.2 Hz, 1H), 7.98 (d, J=6.0 Hz, 1H), 8.54 (d, J=3.3 Hz, 1H), 10.60 (s, 1H), 10.70 (s, 1H); MS (ES) m/z: 621.0 (MH+); HRMS Calcd. for C30H33N6O5S2 (MH+): 621.1954. Found: 621.1952.

Provenance & Evidence