Cesium carbonate → N-(2-(2-Chloro-6-fluorophenyl)thiazolo[5,4-c]pyridin-4-yl)cyclopropanecarboxamide

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Reaction Steps

A mixture of 4-chloro-2-(2-chloro-6-fluoro-phenyl)-thiazolo[5,4-c]pyridine (0.050 g, 0.17 mmol), cyclopropanecarboxamide (0.016 g, 0.18 mmol), Pd2(dba)3 (0.008 g, 0.009 mmol), XantPhos (0.010 g, 0.017 mmol) and cesium carbonate (0.139 g, 0.43 mmol) in dioxane (1.7 mL) was degassed with nitrogen then subjected to microwave irradiation at 170° C. for 60 minutes. Further cyclopropanecarboxamide (0.006 g, 0.08 mmol), Pd2(dba)3 (0.010 g, 0.010 mmol) and XantPhos (0.012 g, 0.021 mmol) were added. The mixture was degassed with nitrogen then subjected to microwave irradiation at 200° C. for 90 minutes. Water and DCM were added and the resulting mixture was filtered through Celite®. The layers of the filtrate were separated via a phase separator and the organic phase concentrated under reduced pressure. The residue was loaded onto an Isolute® SCX-2 cartridge that was washed with MeOH and the product eluted with 2M ammonia in MeOH. The relevant fractions were combined, concentrated under reduced pressure and the resultant residue was purified by silica gel flash chromatography (0-30% EtOAc in DCM) to give the desired compound as an off-white solid (0.018 g, 30% yield). 1H NMR (300 MHz, DMSO-d6): δ 11.40 (s, 1H), 8.45 (d, J=5.6 Hz, 1H), 7.92 (d, J=5.6 Hz, 1H), 7.69 (dd, J=8.3, 6.1 Hz, 1H), 7.59-7.58 (m, 1H), 7.52-7.49 (m, 1H), 2.13-2.03 (s, 1H), 0.91-0.90 (m, 4H). LCMS (Method D): RT=3.36 min, m/z: 348 [M+H+].

Provenance & Evidence