Cesium carbonate → 1-(4-(6-((9-Cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-pyridinyl)-1-piperazinyl)-2-methyl-2-propanol

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To tris(dibenzylideneacetone)dipalladium (0) (0.0190 g, 0.0207 mmol), Xantphos (0.0240 g, 0.0415 mmol), cesium carbonate (0.126 g, 0.387 mmol), 1-(4-(6-chloropyridin-3-yl)piperazin-1-yl)-2-methylpropan-2-ol (251) (0.0746 g, 0.276 mmol), and compound 245 (0.0750 g, 0.276 mmol) was added degassed dioxane (1.1 mL). The reaction was stirred at 105° C. overnight. After 16 h, the reaction was cooled to room temperature and partitioned between dichloromethane (30 mL) and water. The aqueous was brought to pH 12 w/5 N NaOH and extracted further with dichloromethane (15 mL) and 10% methanol in dichloromethane (10 mL). The combined organics were dried with sodium sulfate and concentrated in vacuo. Silica gel chromatography (1% to 5% 2M methanolic NH3 in DCM) afforded compound 250 (0.135 g, 96.8% yield). 1H NMR (500 MHz, DMSO-d6) δ 1.13 (s, 6 H) 1.67-1.81 (m, 2 H) 1.96-2.06 (m, 2 H) 2.07-2.16 (m, 2 H) 2.27 (s, 2 H) 2.33 (d, J=8.56 Hz, 2 H) 2.65-2.74 (m, 4 H) 3.10-3.17 (m, 4 H) 4.14 (s, 1 H) 5.46 (quin, J=9.05 Hz, 1 H) 7.47 (dd, J=9.17, 2.81 Hz, 0 H) 7.97-8.07 (m, 3 H) 8.12 (d, J=9.05 Hz, 0 H) 9.33 (s, 1 H) 9.90 (s, 1 H) ppm.

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