反应详情

A solution of 2-(2-(2-(2,5-dichloropyrimidin-4-yl)ethyl)phenyl)propanamide A30 (50 mg, 0.15 mmol), 4-amino-1-methylpyrazole (15 mg, 0.015 mmol) and p-toluenesulfonic acid (3.0 mg, 0.015 mmol) in 1,4-dioxane (2 mL) was heated at 80° C. under microwave irradiation for 3 hours, then at 120° C. for 3 hours and finally at 140° C. for 2 hours. The mixture was partitioned between water and EtOAc, the layers were separated and the aqueous phase was extracted with EtOAc (3 times). The combined organic extracts were washed with brine, dried (Na2SO4) and the solvent evaporated in vacuo to give the crude product. Purification by silica gel column chromatography (Combiflash Rf, 0-10% MeOH in DCM) gave the title compound 36 as a pale solid (0.020 g, 34%). 1H NMR (300 MHz, CDCl3) δ 1.57 (d, J=7.26 Hz, 3H), 3.04-3.15 (m, 4H), 3.91 (s, 3H), 4.00 (q, J=6.97 Hz, 1H), 5.59 (brs, 2H), 7.19-7.31 (m, 3H), 7.34 (brs, 1H), 7.38-7.41 (m, 1H), 7.49 (s, 1H), 7.71 (s, 1H), 8.25 (s, 1H). LCMS-B: rt 6.09 min; m/z 385 [M+H]+.

1. waitfinally at 140° C. for 2 hours
2. customThe mixture was partitioned between water and EtOAc
3. customthe layers were separated
4. extractionthe aqueous phase was extracted with EtOAc (3 times)
5. washThe combined organic extracts were washed with brine
6. dry with materialdried (Na2SO4)
7. customthe solvent evaporated in vacuo
8. customto give the crude product
9. customPurification by silica gel column chromatography (Combiflash Rf, 0-10% MeOH in DCM)