Cesium carbonate → [2-(2,6-Dichloro-4-methoxyphenyl)thiazolo[5,4-c]pyridin-4-yl]-(6-methylpyrimidin-4-yl)-amine

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-chloro-2-(2,6-dichloro-4-methoxyphenyl)thiazolo[5,4-c]pyridine (0.113 g, 0.328 mmol), 6-methylpyrimidin-4-ylamine (0.031 g, 0.328 mmol), XantPhos (0.019 g, 0.033 mmol), Pd2(dba)3 (0.015 g, 0.0164 mmol) and Cs2CO3 (0.213 g, 0.655 mmol) in dioxane (3 mL) was degassed with a stream of argon and the reaction mixture was heated at 85° C. for 18 hours. After cooling to room temperature and standing at room temperature for 56 hours, additional XantPhos (0.019 g) and Pd2(dba)3 (0.015 g) were added. The resultant mixture was then degassed with a stream of argon and heated at 110° C. for 1 hour using microwave irradiation. Additional XantPhos (0.010 g), Pd2(dba)3 (0.008 g) and 6-methylpyrimidin-4-ylamine (0.006 g) were added and the resulting suspension was then degassed with a stream of argon and heated at 110° C. for 1 hour using microwave irradiation. The crude reaction mixture was filtered through Celite® and the filtrate was concentrated under reduced pressure. The resultant residue was purified by column chromatography on silica gel eluting with 0-2% MeOH in DCM followed by reverse phase HPLC (Phenomenex Gemini 5 μm C18 on a 30 minute gradient 10-80%, 0.1% HCO2H in CH3CN/H2O) to afford the title compound as an off-white solid (36 mg, 26% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.91 (s, 1H), 8.54 (d, J=5.6 Hz, 1H), 7.98 (d, J=5.6 Hz, 1H), 7.73 (s, 1H), 7.36 (s, 2H), 3.92 (s, 3H), 2.49 (s, 3H). LCMS (Method D): RT=3.65 min, m/z: 418 [M+H+].

Provenance & Evidence