Pivalic acid → (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

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence