Cesium carbonate → 3-{3,5-Dichloro-4-[4-(6-methylpyrimidin-4-ylamino)thiazolo[5,4-c]pyridin-2-yl]-phenyl}-azetidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

A mixture of 3-[3,5-dichloro-4-(4-chlorothiazolo[5,4-c]pyridin-2-yl)-phenyl]-azetidine-1-carboxylic acid tert-butyl ester (0.106 g, 0.225 mmol), 6-methylpyrimidin-4-ylamine (0.024 g, 0.248 mmol), XantPhos (0.013 g, 0.023 mmol), Pd2(dba)3 (0.010 g, 0.0113 mmol) and Cs2CO3 (0.147 g, 0.45 mmol) in dioxane (2 mL) was degassed with a stream of argon. The reaction mixture was heated at 85° C. for 18 hours. Additional Pd2(dba)3 (0.005 g), XantPhos (0.007 g) and 6-methylpyrimidin-4-ylamine (0.006 g) were added and the mixture was heated at 85° C. for 18 hours. After cooling to room temperature, 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 0-90% EtOAc in petroleum ether to afford the title compound as a pale yellow glass (64 mg, 52% yield). 1H NMR (400 MHz, CDCl3): δ 8.71 (s, 1H), 8.45 (d, J=5.7 Hz, 1H), 8.15 (s, 1H), 7.76 (d, J=5.6 Hz, 1H), 7.51-7.41 (m, 3H), 4.39 (t, J=8.7 Hz, 2H), 4.02-3.92 (m, 2H), 3.80-3.70 (m, 1H), 2.56 (s, 3H), 1.48 (s, 9H).

Provenance & Evidence