Cesium fluoride → 6-(3-Fluoro-2-pyrazinyl)-2-methyl-4-pyrimidinamine

温度

60 °C

A microwave tube was charged with 6-chloro-2-methyl-4-pyrimidinamine (SynChem, Inc., Des Plaines, Ill.) (0.223 g, 1.550 mmol), PdCl2 (10.99 mg, 0.062 mmol), tri-t-butylphosphonium tetrafluoroborate (0.036 g, 0.124 mmol), CuI (0.024 g, 0.124 mmol) and CsF (0.471 g, 3.10 mmol). The tube was sealed and evacuated under vaccuum and back-filled with N2 (g) 5 times. Argon was bubbled through the tube and 2-fluoro-3-(tributylstannyl)pyrazine (F. Toudic et al. Tetrahedron, 2003, 29, 6375-6384; 1.80 g, 4.65 mmol) in DMF (4 mL) was added and Ar (g) was bubbled through the solution for 5 minutes. The mixture was heated to 60° C. and stirred for 18 h. Water and EtOAc was added and the mixture was filtered through Celite® (diatomaceous earth). The layers were separated and the aqueous layer was extracted with EtOAc (2×). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated. The crude material was adsorbed onto a plug of silica gel and purified by chromatography through a silica gel column (40 g), eluting with a gradient of 0% to 3% MeOH in CH2Cl2. The product was further purified by HPLC (10 to 90% CH3CN and H2O with 0.1% NH4OH, flow rate equal to about 45 mL/min) to afford 6-(3-fluoro-2-pyrazinyl)-2-methyl-4-pyrimidinamine (0.077 g, 0.375 mmol, 24.21% yield) as a white solid. m/z (ESI, +ve) 206.1 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 9.54 (d, J=4.50 Hz, 1H); 8.53 (d, J=8.22 Hz, 1H); 7.26 (s, 1H); 5.58 (br. s., 2H); 2.63 (s, 3H).

1. customThe tube was sealed
2. customevacuated under vaccuum
3. additionback-filled with N2 (g) 5 times
4. additionwas added
5. customAr (g) was bubbled through the solution for 5 minutes
6. additionWater and EtOAc was added
7. filtrationthe mixture was filtered through Celite® (diatomaceous earth)
8. customThe layers were separated
9. extractionthe aqueous layer was extracted with EtOAc (2×)
10. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
11. filtrationfiltered
12. concentrationconcentrated
13. custompurified by chromatography through a silica gel column (40 g)
14. washeluting with a gradient of 0% to 3% MeOH in CH2Cl2
15. customThe product was further purified by HPLC (10 to 90% CH3CN and H2O with 0.1% NH4OH, flow rate equal to about 45 mL/min)

ORDレコード

ord-055ad8d5c2d8480199b0abb1841d5a25

出典データセット

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08362241B2