Pyridine → (+/-)-6-{4-[4-(3-Cyclopentylpropyl)-5-oxo-4,5-dihydrotetrazol-1-yl]phenylsulfamoyl}chroman-2-carboxylic acid amide

Participants

Reaction Conditions

Reaction Steps

Pyridine (650 mL, 8.03 mmol) followed by a solution of 1-(4-aminophenyl)4-(3-cyclopentylpropyl)-5-tetrazolone (2.1 g, 7.32 mmol; prepared as described in WO 97/16189) in tetrahydrofuran (50 mL) were added to a cooled (0° C.) solution of the compound from Example 22 (2.02 g, 7.33 mmol) in tetrahydrofuran (50 mL). The mixture was heated to 50° C. overnight. Pyridine (650 mL) was added and the mixture re-heated to 50° C. After 72 hours the mixture was partitioned between ethyl acetate and water. The organic layer was washed with 5% aqueous hydrochloric acid (2×), saturated aqueous sodium bicarbonate, and saturated aqueous sodium chloride, dried (MgSO4), and concentrated to a solid (3.7 g). The crude was recrystallized from ethyl acetate (260 mL). The recrystallization mixture was cooled to 0° C. before filtering to give colorless crystals (2.14 g). A second crop afforded 1.09 g. The combined yield was 3.22 g (83%). Mp 202-205° C.; 1H NMR (DMSO-d6, 300 MHz) δ 10.43 (s, 1H), 7.69 (d, J=8.8 Hz, 2H), 7.53 (m, 3H), 7.37 (br s, 1H), 7.26 (d, J=8.8 Hz, 2H), 6.95 (d, J=8.5 Hz, 1H), 4.57 (dd, J=8.5 Hz, 3.3 Hz, 1H), 3.92 (t, J=7.0 Hz, 2H), 2.71 (m, 2H), 2.13 (m, 1H), 1.89 (m, 1H), 1.72 (m, 5H), 1.49 (m, 4H), 1.30 (m, 2H), 1.03 (m, 2H); MS (FAB) m/z 527 (MH+).

Provenance & Evidence