反应详情

A mixture of N-[4-chloro-6-(4-fluoro-phenyl)-pyrido[3,2-d]pyrimidin-2-yl]-acetamide (63 mg, 0.2 mmol; the synthesis of which has been disclosed in WO 2006/135993) and iron tris(acetylacetonate) (10 mg, 0.028 mmol) in THF (2 ml) and NMP (1 ml) was added ethylmagnesium bromide (0.6 ml, 0.6 mmol; 1.0 M solution in THF). After stirring at room temperature for 10 minutes, the solution was diluted with THF and quenched by adding a solution of 0.2 N HCl. The mixture was extracted with ethyl acetate, then dried over Na2SO4 and concentrated. The residue was dissolved in methanol (1 ml) and then sodium methoxide (0.2 ml; 0.5 N solution in methanol) was added. The mixture was heated to 120° C. for 10 minutes under microwave irradiation. Solvents were concentrated in vacuo and the residue was purified by HPLC using a C18 column with a gradient of H2O and 0.1% TFA-acetonitrile, to provide the pure title compound as a white solid (1 mg, yield: 2%) which was characterised by its mass spectrum as follows: MS (m/z) 269.0 [M+H]+; HPLC Rt=4.14 minutes (Method A).

1. customthe synthesis of which
2. customquenched
3. additionby adding a solution of 0.2 N HCl
4. extractionThe mixture was extracted with ethyl acetate
5. dry with materialdried over Na2SO4
6. concentrationconcentrated
7. dissolutionThe residue was dissolved in methanol (1 ml)
8. additionsodium methoxide (0.2 ml; 0.5 N solution in methanol) was added
9. temperatureThe mixture was heated to 120° C. for 10 minutes under microwave irradiation
10. concentrationSolvents were concentrated in vacuo
11. customthe residue was purified by HPLC