Water → 4-(2-fluoro-5-(1-morpholinoethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

Participants

Reaction Conditions

Reaction Steps

A glass microwave reaction vessel was charged with 4-chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.433 g, 1.126 mmol), 2-fluoro-5-(1-morpholinoethyl)pyridin-3-ylboronic acid (0.260 g, 1.023 mmol), potassium acetate (0.308 g, 3.14 mmol), Am-Phos (0.051 g, 0.082 mmol), dioxane (3 mL) and water (0.5 mL, 27.8 mmol). The reaction mixture was stirred and heated in a CEM Explorer Microwave Unit for 10 min at 120° C., while 100 Watts of energy was supplied via Powermax® (simultaneous heating while cooling technology). The reaction mixture was diluted with sat. sodium bicarbonate (10 mL) and extracted with chloroform (3×10 mL). The organic extracts were combined and dried over sodium sulfate. The solution was filtered and concentrated in vacuo to give the crude material as a yellow oil. The crude product was adsorbed onto a plug of silica gel and chromatographed through a silica gel column (40 gram), eluting with 50% ethyl acetate/hexanes to give 4-(2-fluoro-5-(1-morpholinoethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.300 g, 0.537 mmol, 52.5% yield) as a light-yellow oil. 1H NMR (400 MHz, d6-DMSO) δ 8.46 (d, J=9.59 Hz, 1H) 8.31 (d, J=1.57 Hz, 1H) 7.25 (d, J=7.63 Hz, 4H) 6.90 (dd, J=10.27, 8.71 Hz, 4H) 4.77 (d, J=13.30 Hz, 3H) 3.66-3.79 (m, 6H) 3.47-3.61 (m, 5H) 3.36 (s, 4H) 3.18 (d, J=5.09 Hz, 1H) 2.49-2.53 (m, 3H) 2.40 (s, 2H) 2.14-2.34 (m, 2H). m/z (ESI, +ve ion) 559.2 (M+H)+.

Provenance & Evidence