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

Participants

Reaction Conditions

Reaction Steps

To a 20 mL microwave reaction tube was added 2-fluoro-5-(2-methoxyethoxy)pyridin-3-ylboronic acid (1.06 g, 4.95 mmol), 4-chloro-6-methyl-1,3,5-triazin-2-amine (Example 9, 0.508 g, 3.51 mmol), Am-Phos (Aldrich, 0.125 g, 0.176 mmol) and potassium acetate (Aldrich, 1.04 g, 10.6 mmol) in EtOH (10 mL) and water (1 mL). The mixture was degassed by bubbling argon through for 5 min. The tube was heated in a microwave reactor (Biotage) at 100° C. for 20 min. The reaction mixture was partitioned between water (50 mL) and EtOAc (50 mL). The aqueous phase was extracted with EtOAc (2×50 mL) and 10% IPA in CHCl3 (3×50 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo. The residue was treated with DCM and the resulting solid was collected to afford 4-(2-fluoro-5-(2-methoxyethoxy)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (0.234 g) as an off-white solid. The filtrate was concentrated and purified by silica gel column chromatography (100 g, eluent: iPrOH in CHCl3 0% to 12.5%) to afford additional material (0.399 g) as a pale yellow solid. Total yield was 0.632 g, 64%. 1H NMR (400 MHz, CDCl3) δ ppm 8.14 (dd, J=7.63, 3.13 Hz, 1H) 8.01 (dd, J=2.93, 1.76 Hz, 1H) 5.56 (br. s., 2H) 4.19-4.27 (m, 2H) 3.75-3.81 (m, 2H) 3.46 (s, 3H) 2.53 (s, 3H).

Provenance & Evidence