3-Isopropoxypropylamine → 5-{2-Fluoro-4-[(3-isopropoxypropylamino)methyl]phenoxy}pyrazine-2-carboxamide

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Reaction Steps

Place 5-(2-fluoro-4-formylphenoxy)pyrazine-2-carboxamide (Example 737, Part E) (0.400 g, 1.53 mmol), 3-isopropoxypropylamine (0.197 g, 1.68 mmol) and 3 Å molecular sieves in a vial. Add methanol (7.7 mL), cap and stir overnight. Add NaBH4 (0.058 g, 1.53 mmol) 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 30% (2.0 M NH3 in methanol) in 80% (ethyl acetate in hexanes). Concentrate the fractions containing the product. Take the solid tip in dichloromethane (100 mL) and wash with 1.0 N NaOH (2× 25 mL) to give the title compound (0.395 g, 71%): TOF MS ES+ 363.2 (M+H)+, HRMS calcd for C18H24N4O3F 363.1832 (M+H)+, found 363.1821, time 0.57 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 min, 20-95% over 18], tR=9.8 ml, 100% purity.

Provenance & Evidence