反应详情

A mixture of 2-(2-(2-(2-chloro-5-methylpyrimidin-4-yl)ethyl)phenyl)propanamide A49 (0.250 g, 0.823 mmol), 1-methyl-1H-pyrazol-4-amine (0.096 g, 0.99 mmol), and p-toluenesulfonic acid monohydrate (0.016 g, 0.082 mmol) in 1,4-dioxane (5 mL) was irradiated in the microwave at 120° C. for 3 hours. The volatiles were removed in vacuo and the residue was adsorbed onto silica and purified by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 50-100% EtOAc in petroleum benzine 40-60° C., then 0-10% MeOH in EtOAc). The fractions containing suspected product were combined and the solvent removed in vacuo to give a green solid. The solid was adsorbed onto silica and purified by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-10% MeOH in CHCl3) to give the title compound 51 as a white solid (0.178 g, 59%); 1H NMR (400 MHz, d6-DMSO) δ ppm 9.16 (s, 1H), 8.11 (s, 1H), 7.85 (s, 1H), 7.46 (s, 1H), 7.41-7.35 (m, 1H), 7.24 (s, 1H), 7.20-7.10 (m, 3H), 6.87 (s, 1H), 3.86 (q, J=7.1, 7.0, 7.0 Hz, 1H), 3.78 (s, 3H), 3.23-3.11 (m, 1H), 3.08-2.97 (m, 1H), 2.96-2.78 (m, 2H), 2.05 (s, 3H), 1.33 (d, J=6.9 Hz, 3H). LCMS-D: rt 2.99 min; m/z 365 [M+H]+.

1. customwas irradiated in the microwave at 120° C. for 3 hours
2. customThe volatiles were removed in vacuo
3. custompurified by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 50-100% EtOAc in petroleum benzine 40-60° C.
4. additionThe fractions containing suspected product
5. customthe solvent removed in vacuo
6. customto give a green solid
7. custompurified by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-10% MeOH in CHCl3)