Cesium carbonate → Methyl 1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-3-carboxylate

Participants

Reaction Steps

To a solution of (5-chloro-thiazolo[5,4-d]pyrimidin-7-yl)-(3,4-dimethoxy-phenyl)-amine (80 mg, 0.25 mmol) in 10 mL of dioxane, methyl piperidine-3-carboxylate (107 mg, 0.75 mmol), Cs2CO3 (163 mg, 0.50 mmol), X-Phos (47.6 mg, 0.1 mmol) were added. After degassed three times under nitrogen, Pd2(dba)3 (28 mg, 0.05 mmol) was added. The resulting mixture was degassed one more time, and stirred at reflux overnight. The excess of dioxane was removed under reduced pressure and the residue was purified by silica gel chromatography (200-300 mesh, petroleum ether:ethyl acetate=1:1) to give methyl 1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-3-carboxylate (60 mg, 56%) as an oil, which was solidified after standing overnight. 1H NMR (300 MHz, CDCl3): δ 8.41 (s, 1H), 7.77 (s, 1H), 7.64 (s, 1H), 7.08 (d, 1H, J=9.0 Hz), 6.88 (d, 1H, J=8.7 Hz), 4.92-4.87 (m, 1H), 4.68-4.64 (m, 1H), 3.93 (s, 3H), 3.91 (s, 3H), 3.71 (s, 3H), 3.30-3.22 (m, 1H), 3.10-3.09 (m, 1H), 2.60-2.59 (m, 1H), 2.11-2.06 (m, 1H), 1.85-1.60 (m, 3H). LC-MS: 430.1 [M+H]+, 452.1 [M+Na]+, tR=1.63 min.

Provenance & Evidence