p-Fluorophenethylamine → 5-(4-{[2-(4-Fluorophenyl)ethylamino]methyl}phenoxy)pyridine-2-carboxamide

Participants

Reaction Steps

Suspend 5-(4-formylphenoxy)pyridine-2-carboxamide (0.0271 g, 0.112 mmol) in methanol (2.1 mL). Add 4-fluorophenethylamine (0.015 mL, 0.112 mmol) and 3 Å molecular sieves. Stir at room temperature overnight. Add NaBH4 (in small excess) and stir for additional 3 hours. Load the reaction mixture directly onto a 5 g SCX column. Wash the column with methanol and elute with 2.0 M NH3 in methanol. Purify by flash chromatography, eluting with 70% ethyl acetate, 5% (2.0 M NH3 in methanol) and 25% hexanes to give the title compound (0.0370 g, 90.5%): TOF MS ES+ 366.2 (M+H)+, base peak TOF MS ES+ 227.1 (M−NHCH2CH2C6H4F)+, HRMS calcd for C21H21N3O2F 366.1618 (M+H)+, found 366.1621, time 0.42 min; HPLC [YMC-Pack Pro C-18 (150×4.6 mm, S-5 microm), 0.1% TFA/acetonitrile in 0.1% TFA/water at 1.0 mL/min, 5-95% over 19 min], tR=10.2 min, 100% purity.

Provenance & Evidence