反应详情

Place 5-(4-formyl-2-methoxyphenoxy)pyrazine-2-carboxamide (Example 719, Part A) (0.700 g, 2.56 mmol), 4,4-dimethylpentylamine (0.310 g, 2.69 mmol) and 3 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, then add EtOAc (100 mL). Wash the organic solution with 1.0 N NaOH (2×25 mL), dry it over Na2SO4, filter and concentrate. Dissolve the product in ether:dichloromethane (5:1) (25 mL), add hexanes (20 mL), and then concentrate to about a quarter of the volume. Filter the precipitate to give the title compound (0.356 g, 37.3%): TOF MS ES+ 373.2 (M+H)+, HRMS calcd for C20H29N4O3 373.2240 (M+H)+, found 373.2245, time 0.39 man; 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 min, 10-20% over 5 min, 20-95% over 18], tR=12.0 min, 98.7% 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. washWash the organic solution with 1.0 N NaOH (2×25 mL)
7. dry with materialdry it over Na2SO4
8. filtrationfilter
9. concentrationconcentrate
10. dissolutionDissolve the product in ether:dichloromethane (5:1) (25 mL)
11. additionadd hexanes (20 mL)
12. concentrationconcentrate to about a quarter of the volume
13. filtrationFilter the precipitate