Pentylamine → 5-(2-Fluoro-4-pentylaminomethylphenoxy)pyridine-2-carboxamide

Participants

Reaction Steps

Place 5-(2-fluoro-4-formylphenoxy)pyridine-2-carboxamide (Example 403, Part B) (0.040 g, 0.154 mmol) amylamine (0.0139 g, 0.154 mmol) and 3 Å molecular sieves in a vial. Add methanol (1.5 mL), cap and stir overnight. Add NaBH4 (in excess over two portions) and stir until the gasses stop evolving. Load directly onto a 5 g SCX column. Wash with methanol (10 mL), then elute with 2.0 M NH3 in methanol. Purify by loading the product onto a 5 g loading cartridge and eluting through a 10 g ISCO® column with 50% ethyl acetate, 5% (2.0 M NH3 in methanol) and 45% hexanes to give the title compound (0.0387 g, 76.0%: TOF MS ES+ 332.2 (M+H)+, HRMS calcd for C18H23N3O2F 332.1774 (M+H)+, found 332.1765, time 0.39 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, 20-99% over 23 min], tR=6.9 min, 100% purity.

Provenance & Evidence