Cesium carbonate → {3,5-Dichloro-4-[4-(6-methyl-pyrimidin-4-ylamino)-thiazolo[5,4-c]pyridin-2-yl]-phenyl}-methanol

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Reaction Steps

A mixture of [3,5-dichloro-4-(4-chloro-thiazolo[5,4-c]pyridin-2-yl)-phenyl]-methanol (0.063 g, 0.18 mmol), 4-amino-6-methylpyrimidine (0.022 g, 0.20 mmol), Pd2(dba)3 (0.003 g, 3.6 mmol), XantPhos (0.003 g, 5.0 pmol) and cesium carbonate (0.117 g, 0.36 mmol) in dioxane (1.1 mL) was degassed with nitrogen and subjected to microwave irradiation at 150° C. for 30 minutes. Further 4-amino-6-methylpyrimidine (0.011 g, 0.10 mmol), Pd2(dba)3 (0.006 g, 7.2 pmol), and XantPhos (0.006 g, 10.0 pmol) were added and the mixture subjected to further microwave irradiation at 150° C. for 60 minutes. The reaction mixture was diluted with MeOH and passed through a nylon filter. The filtrate was concentrated under reduced pressure then loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M ammonia in MeOH. The eluent was concentrated under reduced pressure and the resultant residue was purified by silica gel flash chromatography eluting with 0-100% EtOAc in DCM to give the desired compound as a yellow solid (0.030 g, 40% yield). 1H NMR (300 MHz, CDCl3): δ 8.68 (s, 1H), 8.42 (br s, 1H), 8.18-8.04 (m, 1H), 7.77 (d, J=5.7 Hz, 1H), 7.50 (s, 2H), 4.72 (s, 2H), 2.55 (s, 3H). LCMS (Method C): RT=2.90 min, m/z: 418 [M+H+].

Provenance & Evidence