反应详情

温度

100 °C

To microwave vial were added 6-bromo-N-(4-(1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl)pyridin-2-yl)-4-methylpyridin-2-amine (247 mg, 0.547 mmol), (R)-methyl 5-hydroxy-5-(thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-2-carboxylate (158 mg, 0.547 mmol), butyldi-1-adamantylphosphine (78 mg, 0.219 mmol), CsF (249 mg, 1.64 mmol), pivalic acid (95 μl, 0.821 mmol), and Pd(OAc)2 (24.6 mg, 0.109 mmol). The reaction was vacuum and purged with argon 3 times, then degassed 1,4-Dioxane (2.0 mL) was added and the reaction was heated to 100° C. for 16 h. The reaction was cooled to rt and diluted with EtOAc (20 mL). The reaction was filtered, concentrated and purified by silica gel chromatography using a gradient solvent system of 30-100% EtOAc/Hexanes. The product-containing fractions were collected and concentrated to give (R)-methyl 5-hydroxy-5-(5-(6-((4-(1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl)pyridin-2-yl)amino)-4-methylpyridin-2-yl)thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-2-carboxylate (121 mg, 34%) as a white foam. MS ESI calcd for C36H33N7O4S [M+H]+ 660, found 660.

1. custompurged with argon 3 times
2. additiondegassed 1,4-Dioxane (2.0 mL) was added
3. temperatureThe reaction was cooled to rt
4. additiondiluted with EtOAc (20 mL)
5. filtrationThe reaction was filtered
6. concentrationconcentrated
7. custompurified by silica gel chromatography
8. customThe product-containing fractions were collected
9. concentrationconcentrated