5-Bromo-2-methylimidazo[1,2-a]pyridine → 2-Methyl-2-(4-((2-(2-methylimidazo[1,2-a]pyridin-5-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)propanamide

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-[4-(4-morpholin-4-yl-2-(tributylstannanyl)thieno[3,2-d]pyrimidin-6-yl methyl)piperazin-1-yl]isobutyramide (150 mg, 0.21 mmol), 5-bromo-2-methyl-imidazo[1,2-a]pyridine (55 mg, 0.26 mmol), Pd(PPh3)4 (24 mg, 0.02 mmol) and copper(I) thiophene-2-carboxylate (8 mg, 0.04 mmol) in dioxane (2 mL) was purged with argon gas then heated at 150° C., for 20 min, in a microwave reactor. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was washed with MeOH then the desired product eluted with 2 M NH3 in MeOH. The resulting residue was purified by flash chromatography (Si—PPC, MeOH:DCM, gradient 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 693 as a white solid (55 mg, 47%). LCMS (Method E): RT 4.99 min; [M+H]+ 535. 1H NMR (400 MHz, CHCl3-d): δ 8.98 (s, 1 H); 7.92-7.89 (m, 1 H); 7.68 (d, J=8.8 Hz, 1 H); 7.39 (s, 1 H); 7.27-7.23 (m, 1 H); 7.09 (d, J=5.3 Hz, 1 H); 5.22 (d, J=5.3 Hz, 1 H); 4.09-4.04 (m, 4 H); 3.94-3.87 (m, 4 H); 3.87 (s, 2 H); 2.62 (m, 8 H); 2.54 (s, 3 H); 1.29-1.23 (m, 6 H)

Provenance & Evidence