Diisopropylamine → 5-[5-(3-{[4-(2-{[Tert-butyl(dimethyl)silyl]oxy}ethoxy)pyrimidin-2-yl]amino}-5-methylphenyl)-1,3-thiazol-2-yl]-2,2-dimethyl-1,3-dioxan-5-ol

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Reaction Conditions

Reaction Steps

To diisopropyl amine (185 μL, 1.29 mmol) in tetrahydrofuran (2.2 mL) at 0° C. was added n-butyllithium (2.2 M in hexanes, 589 μL, 1.29 mmol). The mixture was stirred for 15 minutes, then cooled to −78° C. 4-(2-{[tert-butyl(dimethyl)silyl]oxy}ethoxy)-N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]pyrimidin-2-amine (191 mg, 0.43 mmol), dissolved in tetrahydrofuran (1 mL), was added dropwise over 5 minutes. The mixture was stirred for 30 minutes at −78° C., then 2,2-dimethyl-1,3-dioxan-5-one (57 μL, 0.47 mmol) was added dropwise. The reaction was stirred for 2 h, and then quenched with saturated aqueous ammonium chloride. The mixture was extracted with ethyl acetate (3×), and the combined organic fractions were dried over sodium sulfate, filtered, and concentrated. Purification by column chromatography on silica gel (Biotage 25 G, eluting with 0:100 to 100:0 ethyl acetate:hexanes) gave 5-[5-(3-{[4-(2-{[tert-butyl(dimethyl)silyl]oxy}ethoxy)pyrimidin-2-yl]amino}-5-methylphenyl)-1,3-thiazol-2-yl]-2,2-dimethyl-1,3-dioxan-5-ol (185 mg, 0.32 mmol, 75% yield) as a pale yellow solid. MS ESI: [M+H]+ m/z 573.3.

Provenance & Evidence