反应详情

温度

120 °C

A glass microwave reaction vessel was charged with 5-(1-((R)-4-(tert-butoxycarbonyl)-2-methylpiperazin-1-yl)ethyl)-2-fluoropyridin-3-ylboronic acid (1.4 g, 3.81 mmol),4-chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (1.467 g, 3.81 mmol),1,4-dioxane (10 mL, 3.81 mmol), potassium acetate (1.122 g, 11.44 mmol), water (1 mL, 3.81 mmol), and amphos (0.270 g, 0.381 mmol). The reaction mixture was stirred and heated in a microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 120° C. for 20 min (watts, Powermax feature, ramp time min). LC/MS showed desired product, starting triazine and debornated product. The reaction mixture was diluted with water (20 mL) and DCM (25 mL) and the aqueous layer was extracted with DCM (3×50 mL) dried over sodium sulfate, filtered and concentrated in vacuum. The crude product was adsorbed onto a plug of silica gel and chromatographed through a silica gel column (40 g), eluting with a gradient of 0% to 50% EtOAc in hexane, to provide (3R)-tert-butyl 4-(1-(5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-fluoropyridin-3-yl)ethyl)-3-methylpiperazine-1-carboxylate (1.26 g, 1.876 mmol, 49.2% yield).

1. customA glass microwave reaction vessel