5-Bromoimidazo(1,2-a)pyridine → 4-(5-(Imidazo[1,2-a]pyridin-5-yl)-2-((3-morpholinoazetidin-1-yl)methyl)thiazolo[5,4-d]pyrimidin-7-yl)morpholine

Participants

Reaction Steps

A mixture of 7-morpholin-4-yl-2-(3-morpholin-4-ylazetidin-1-ylmethyl)-5-(tributylstannanyl)thiazolo[5,4-d]pyrimidine (0.25 g, 0.37 mmol), 5-bromoimidazo[1,2-a]pyridine (0.082 g, 0.41 mmol), copper(I) 2-thiophene carboxylate (0.015 g, 0.075 mmol) and Pd(PPh3)4 (0.044 g, 0.037 mmol) in dioxane (3 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 residue was purified by flash chromatography (Si—PPC, MEOH:DCM, 0:100 to 10:90) 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 700 as a yellow solid (0.101 g, 55%). LCMS (Method E): RT=3.98 min, [M+H]+ 493.15. 1H NMR (CDCl3, 400 MHz) δ 9.16 (s, 1 H); 7.98 (dd, J=7.2, 1.2 Hz, 1 H); 7.81 (d, J=8.9 Hz, 1 H); 7.76 (d, J=1.2 Hz, 1 H); 7.33 (dd, J=8.9, 7.2 Hz, 1 H); 4.47-4.32 (m, 4 H); 4.04 (s, 2 H); 3.89 (t, J=4.6 Hz, 4 H); 3.74 (t, J=4.6 Hz, 4 H); 3.69 (t, J=6.4 Hz, 2 H); 3.23-3.15 (m, 2 H); 3.14 (t, J=6.4 Hz, 1 H); 2.40-2.36 (m, 4 H)

Provenance & Evidence