Cesium carbonate → HCID 67387473, compound

Participants

Reaction Conditions

Reaction Steps

A vial was charged with pyridin-3-ylboronic acid (0.027 g, 0.222 mmol), PdCl2(dppf)-CH2Cl2-adduct (8.65 mg, 10.59 μmol), (S)-3-bromo-7-iodo-2′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,3′-[1,4]oxazin]-5′-amine (0.100 g, 0.212 mmol), and potassium carbonate (0.117 g, 0.847 mmol). Dioxane (5 mL) and water (0.5 mL) were added. The vial was flushed with argon, and heated to 100° C. for 1 hour. An additional portion of pyridin-3-ylboronic acid (0.027 g, 0.222 mmol) was added, and the reaction mixture was heated to 100° C. for an additional hour. The reaction mixture was diluted with 2-MeTHF, dried over MgSO4 and concentrated under reduced pressure. The crude residue was used without purification. Step 2: The crude residue from step 1 was dissolved in 2 mL DMF, treated with 3,3-dimethyl-1-butyne (0.130 mL, 1.059 mmol), cesium carbonate (0.345 g, 1.059 mmol), and tBu-XPhos palladacycle (7.27 mg, 10.59 μmol). The reaction mixture was capped under argon, and was heated to 90° C. for 2 hours. The reaction mixture was then diluted with 2-MeTHF and washed with water. The organics were dried over MgSO4 and concentrated. Purification of the crude residue by column chromatography [0-100% (95:5 EtOAc/MeOH)/DCM] gave (S)-3-(3,3-dimethylbut-1-ynyl)-7-(pyridin-3-yl)-2′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,3′-[1,4]oxazin]-5′-amine (0.018 g, 0.042 mmol, 20.02% yield) as a grey solid. [M+H]+=425.0

Provenance & Evidence