Hydrochloric Acid → (+/-)-2-Aminomethylchroman-6-sulfonic acid {4-[4-(3-cyclopentylpropyl)-5-oxo-4,5-dihydrotetrazol-1-yl]phenyl}amide

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Reaction Conditions

Reaction Steps

Borane-methyl sulfide complex (2.0 M solution in tetrahydrofuran, 17.1 mL, 34.2 mmol) was added to a cooled (0° C.) solution of the compound from Example 23 (3.0 g, 5.70 mmol) in tetrahydrofuran (75 mL). The mixture was heated to reflux for 90 minutes then cooled to 0° C. Methanol was added until gas evolution ceased, then 6N HCl (15 mL) was added. The mixture was heated to reflux for 60 minutes then cooled to 0° C. The mixture was brought to pH=12 with 10% aqueous sodium hydroxide and extracted with ethyl acetate (2×). the combined organic layers were dried (Na2SO4) and concentrated to a solid. Silica gel chromatography (gradient elution from 50:50 hexane/ethyl acetate to 45:45:10 hexane/ethyl acetate/methanol to 90:10 ethyl acetate/methanol) afforded a colorless solid (2.32 g, 80%). Mp 125-130° C. (dec); 1H NMR (DMSO- d6, 300 MHz) δ 7.64 (d, J=8.8 Hz, 2 H), 7.54 (d, J=2.2 Hz, 1 H), 7.47 (dd, J=8.5 Hz, 2.2 Hz, 1 H), 7.22 (d, J=8.8 Hz, 2 H), 6.84 (d, J=8.8 Hz, 1 H), 5.6 (br s, 3 H), 4.04 (m, 1 H), 3.92 (t, J=7.0 Hz, 2 H), 2.83 (d, J=5.5 Hz, 2 H), 2.76 (m, 2 H), 2.0 (m, 1 H), 1.8-1.4 (m, 10 H), 1.30 (m, 2 H), 1.03 (m, 2 H); MS (FAB) m/z 513 (MH+).

Provenance & Evidence