反应详情

Place 5-(4-formyl-2-methoxyphenoxy)pyrazine-2-carboxamide (Example 719, Part A) (0.700 g, 2.56 mmol), isoamylamine (0.234 g, 2.69 mmol) and 3 {acute over (Å)} molecular sieves in a vial. Add methanol (12.8 mL), cap and stir overnight. Add NaBH4 (0.0969 g, 2.56 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 20% (2.0 M NH3 in methanol) in ethyl acetate over 45 minutes. Concentrate the fraction containing the product, and dissolve it in EtOAc (100 mL). Wash the organic solution with 1.0 N NaOH (2×25 mL), dry it over Na2SO4, filter and concentrate to give the title compound (0.484 g, 54.9%): TOF MS ES+ 345.2 (M+H)+, HRMS calcd for C18H25N4O3 345.1927 (M+H)+, found 345.1938, time 0.38 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=10.1 min, 95.4% purity.

1. customDry the column in a vacuum oven at room temperature
2. customPurify
3. washby eluting through a 40 g ISCO® column with 5% to 20% (2.0 M NH3 in methanol) in ethyl acetate over 45 minutes
4. concentrationConcentrate the fraction
5. additioncontaining the product
6. dissolutiondissolve it in EtOAc (100 mL)
7. washWash the organic solution with 1.0 N NaOH (2×25 mL)
8. dry with materialdry it over Na2SO4
9. filtrationfilter
10. concentrationconcentrate