3-Bromo-2-fluoro-4-iodopyridine → 5-(3-Bromo-2-fluoropyridin-4-yl)-N4-(cyclopropylmethyl)pyrimidine-2,4-diamine

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Isopropylmagnesium chloride, 2 M solution in THF (0.814 mL, 1.63 mmol) was added dropwise over 15 minutes to a degassed solution of 3-bromo-2-fluoro-4-iodopyridine (0.468 g, 1.55 mmol) in Et2O (0.150 mL) and THF (0.850) cooled at −78° C. The solution was stirred for 0.5 h. Zinc chloride, 1.0 M solution in diethyl ether (0.776 mL, 0.776 mmol) was then added dropwise to the reaction over 10 minutes. The reaction was allowed to reach room temperature. The reaction warmed to room temperature within 15 min. A solution of compound 238 (0.150 g, 0.517 mmol) and tetrakis(triphenylphosphine)palladium (0.0418 g, 0.0362 mmol) in THF (0.50 mL) was added to the reaction. The reaction was equipped with a reflux condenser and stirred in a 60° C. oil bath. After 2 h the reaction was removed from heat and allowed to stand overnight. Saturated NH4Cl (0.5 mL) and 12% 2-propanol in CH2Cl2 (2 mL) were added. The organics were sequestered and the aqueous was extracted with 12% 2-propanol in CH2Cl2 (4×4 mL). The combined organics were washed with brine, dried over MgSO4, and concentrated in vacuo. Silica gel chromatography (elution 3% methanol in DCM with 0.175% NH4OH additive) afforded compound 240 (0.140 g, 80.1% yield). 1H NMR (500 MHz, CDCl3) δ ppm 0.22 (d, J=4.40 Hz, 2 H) 0.46-0.59 (m, 2H) 0.96-1.07 (m, 1H) 3.21-3.36 (m, 2 H) 4.51 (br. s., 1 H) 5.11 (br. s., 2 H) 7.16 (d, J=4.89 Hz, 1H) 7.69 (s, 1 H) 8.22 (d, J=4.89 Hz, 1 H) ppm.

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