反应详情

温度

120 °C

To a stirred solution of 3-(3,5-dibromo-2-oxo-2H-pyrazin-1-yl)-4-methyl-benzoic acid methyl ester (Example 1b, 0.4 g) in tetrahydrofuran (3 mL) within a microwave vial was added N,N-diisopropylethylamine (200 μL) and α,α-dimethyl-2-(phenylmethoxy)-benzenemethanamine (360 mg). The reaction was heated in a microwave for 100 minutes at 120° C. The reaction mixture was cooled to room temperature and cyclopropylamine (0.5 mL) was added. A solution of cyclopentylmagnesium bromide (2M in diethyl ether, 3 mL) was added dropwise. The reaction mixture was stirred for 30 minutes. Ethanol (2 mL) and sat. aqueous NH4Cl were added and the mixture extracted with ethyl acetate. The pooled organic were washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. The residue was taken up in ethanol (3 mL) and ammonium formate (0.3 g) and 10% palladium on carbon (40 mg) were added. The reaction mixture was heated within a microwave for 30 minutes at 100° C. and then 90 minutes at 60° C. before being cooled to room temperature, then filtered and washed with ethanol. The filtrate was concentrated in vacuo. The residue was purified (SiO2 chromatography eluting with iso-hexane:ethyl acetate) to afford the subtitle compound as a solid (330 mg).

1. temperatureThe reaction mixture was cooled to room temperature
2. extractionthe mixture extracted with ethyl acetate
3. washThe pooled organic were washed with brine
4. dry with materialdried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. additionammonium formate (0.3 g) and 10% palladium on carbon (40 mg) were added
8. temperatureThe reaction mixture was heated within a microwave for 30 minutes at 100° C.
9. temperature90 minutes at 60° C. before being cooled to room temperature
10. filtrationfiltered
11. washwashed with ethanol
12. concentrationThe filtrate was concentrated in vacuo
13. customThe residue was purified
14. wash(SiO2 chromatography eluting with iso-hexane:ethyl acetate)