反应详情

Place 5-(4-formyl-2-methylphenoxy)pyrazine-2-carboxamide (Example 404, Part D) (0.200 g, 0.777 mmol), 2-(tetrahydropyran-4-yl)ethylamine (0.100 g, 0.777 mmol) and 3 Å molecular sieves in a vial. Add methanol (3.8 mL) cap and stir overnight. Add NaBH4 (in excess over two portions) and stir until the gasses stop evolving. Load the reaction mixture directly onto a 5 g ISCO® pre-load column. Dry the pre-loaded column in a vacuum oven at room temperature. Purify by eluting through a 10 g ISCO® column with (2.0 M NH3 in methanol), ethyl acetate and hexanes. After concentrating, take the product up in CH2Cl2 (25 mL) and wash with 1.0 N NaOH solution (2× 10 mL). Dry the organic layer over Na2SO4, filter and concentrate to give the title compound (0.121 g, 42.0%): MS ES+ 371.1 (M+H)+, base peak 242.0 (M-C7H14NO)+; 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/in, 5-95% over 19 min], tR=7.9 min, 100% purity.

1. customDry the pre-loaded column in a vacuum oven at room temperature
2. customPurify
3. washby eluting through a 10 g ISCO® column with (2.0 M NH3 in methanol), ethyl acetate and hexanes
4. concentrationAfter concentrating
5. washwash with 1.0 N NaOH solution (2× 10 mL)
6. dry with materialDry the organic layer over Na2SO4
7. filtrationfilter
8. concentrationconcentrate