2-(Oxan-4-yl)ethan-1-amine → 5-(4-{[2-(Tetrahydropyran-4-yl)ethylamino]methyl}phenoxy)thiophene-2-carboxamide

Participants

Reaction Steps

Place 5-(4-formylphenoxy)thiophene-2-carboxamide (Example 10, Part C) (0.235 g, 0.948 mmol), 2-(tetrahydropyran-4-yl)ethylamine (0.122 g, 0.996 mmol) and 3 Å molecular sieves in a vial. Add methanol (4.7 mL), cap and stir overnight. Add NaBH4 (0.0359 g, 0.948 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 5% to 30% (2.0 M NH3 in methanol) in ethyl acetate over 45 minutes to give the title compound: TOF MS ES+ 361.2 (M+H)+, HRMS calcd for C19H25N2O3S 361.1586 (M+H)+, found 361.1604, time 0.36 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=9.4 min, 100% purity.

Provenance & Evidence