5-Bromoimidazo(1,2-a)pyridine → 2-(1-((2-(imidazo[1,2-a]pyridin-5-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)piperidin-4-yl)propan-2-ol

Participants

Reaction Steps

A mixture of 2-[1-(9-methyl-6-morpholin-4-yl-2-(tributylstannanyl)-9H-purin-8-ylmethyl)piperidin-4-yl]propan-2-ol (0.2 g, 0.30 mmol), 5-bromoimidazo[1,2-a]pyridine (0.066 g, 0.33 mmol), copper(I) 2-thiophene carboxylate (0.018 g, 0.09 mmol) and Pd(PPh3)4 (0.052 g, 0.045 mmol) in dioxane (5 mL) was subjected to microwave irradiation at 150° C. for 60 min. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the desired product was eluted using 2 M NH3 in MeOH. The eluent was concentrated in vacuo and the resultant residue was purified by flash chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 94:6) followed by reverse phase HPLC (Phenomenex Gemini 5u C18, 20 mM triethylamine in water on a gradient of acetonitrile 95:5 to 2:98) to give 698 as a yellow powder (0.085 g, 58%). LCMS: RT=4.17 min, [M+H]+ 491.2. 1H NMR (CDCl3, 400 MHz) δ 9.26 (d, J=1.2 Hz, 1 H); 7.96 (dd, J=8.2, 1.2 Hz, 1 H); 7.76-7.73 (m, 2 H); 7.31 (dd, J=8.2, 5.2 Hz, 1 H); 4.38 (t, J=4.6 Hz, 4 H); 3.96 (s, 3 H); 3.89 (t, J=4.6 Hz, 4 H); 3.75 (s, 2 H); 2.96 (d, J=11.0 Hz, 2 H); 2.11 (t, J=11.0 Hz, 2 H); 1.76 (d, J=11.0 Hz, 2 H); 1.44-1.29 (m, 3 H); 1.18 (s, 6 H)

Provenance & Evidence