1,2-Dimethoxyethane → 4-(1-(6-Fluoro-5-(2-methyl-6-(methylthio)pyrimidin-4-yl)pyridin-3-yl)ethyl)morpholine

Participants

Reaction Conditions

Reaction Steps

To a 20 mL microwave vials was added 4-chloro-2-methyl-6-(methylthio)pyrimidine (0.175 g, 1.002 mmol), 2-fluoro-5-(1-morpholinoethyl)pyridin-3-ylboronic acid (Example 339 Step 3) (0.305 g, 1.202 mmol), trans-dichlorobis(triphenyl-phosphine)palladium (II) (Strem) (0.056 g, 0.080 mmol), sodium carbonate (JT Baker) (0.531 mg, 5.01 mmol), DME (10 mL), and water (2.5 mL). The vial was degassed by bubbling N2 for 5 min then sealed off and microwave heated at 90° C. for 20 min. The reaction mixture was partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc (2×10 mL). The combined organic layers were dried over MgSO4 and concentrated. The crude product was purified by column chromatography (40 g, 10% to 20% acetone in hexanes) to afford the product as white solid (275 mg). MS (ESI pos. ion) m/z: 349.1. 1H NMR (300 MHz, CDCl3) δ ppm 1.43 (d, J=6.72 Hz, 3H) 2.33-2.46 (m, 2H) 2.48-2.58 (m, 2H) 2.61 (s, 3H) 2.74 (s, 3H) 3.52 (q, J=6.58 Hz, 1H) 3.71 (t, J=4.46 Hz, 4H) 7.55 (s, 1H) 8.25 (s, 1H) 8.56 (dd, J=9.43, 2.27 Hz, 1H).

Provenance & Evidence