Sodium borohydride → 5-{4-[(2-Cyclopentylethylamino)methyl]-2-fluorophenoxy}pyridine-2-carboxamide

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Reaction Steps

Place 5-(2-fluoro-4-formylphenoxy)pyridine-2-carboxamide (Example 403, Part B) (0.650 g, 2.50 mmol), 2-cyclopentylethylamine (0.792 g, 2.75 mmol) and 3 Å molecular sieves in a vial. Add methanol (12 mL), cap and stir overnight. Add NaBH4 (slight excess) and stir until the gasses stop evolving. Load the reaction mixture directly onto a 25 g ISCO® pre-load column. Dry the column in a vacuum oven at room temperature. Purify by eluting through a 40 g ISCO® column with 0% to 10% (2.0 M NH, in methanol) in ethyl acetate to give the title compound (0.0850 g, 10%): TOF MS ES+ 358.2 (M+H)+, HRMS calcd for C20H25N3O2F 358.1931 (M+H)+, found 358.1925, time 0.48 min; HPLC [YMC-Pro pack C-18 (150×4.6 mm, S-5 microm), 0.05% TFA/acetonitrile in 0.05% TFA/water at 1.0 mL/min, 10-20% over 5 ml, 20-95% over 18], tR=11.8 min, 94.2% purity.

Provenance & Evidence