4-Chloro-6-methyl-1,3,5-triazin-2-amine → 4-(2-Fluoro-5-(1-morpholinoethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine

Participants

Reaction Conditions

Reaction Steps

To a 20 mL microwave vial was added 4-chloro-6-methyl-1,3,5-triazin-2-amine (0.300 g, 2.075 mmol), 2-fluoro-5-(1-morpholinoethyl)pyridin-3-ylboronic acid (0.580 g, 2.283 mmol), Amphos (Aldrich) (0.073 g, 0.104 mmol), potassium acetate (Aldrich) (0.611 g, 6.23 mmol), EtOH (9 mL), and water (0.9 mL). The resulting mixture was degassed by bubbling N2 for 5 min then sealed off and microwave heated at 100° C. for 20 min. The reaction mixture was partitioned between 25% IPA in CHCl3 (1% NH4OH) (30 mL) and water (50 mL). The aqueous layer was extracted with more 25% IPA in CHCl3 (2×10 mL). The combined organic layers were dried over MgSO4 and concentrated. The crude product was purified by column chromatography (40 g, 3% MeOH in DCM) to afford the desired product as a white solid (200 mg). MS (ESI pos. ion) m/z: 319.1. 1H NMR (300 MHz, CDCl3) δ ppm 1.42 (d, J=6.58 Hz, 3H) 2.32-2.47 (m, 2H) 2.49-2.63 (m, 5H) 3.50 (q, J=6.33 Hz, 1H) 3.71 (t, J=4.38 Hz, 4H) 5.49 (br. s., 2H) 8.29 (s, 1H) 8.46 (dd, J=9.13, 2.27 Hz, 1H).

Provenance & Evidence