Cesium carbonate → 2-(1-((5-(2-ethyl-1H-benzo[d]imidazol-1-yl)-7-morpholinothiazolo[5,4-d]pyrimidin-2-yl)methyl)piperidin-4-yl)propan-2-ol

Participants

Reaction Steps

A mixture 2-[1-(5-chloro-7-morpholin-4-ylthiazolo[5,4-d]pyrimidin-2-ylmethyl)piperidin-4-yl]propan-2-ol (100 mg, 0.24 mmol), 2-ethyl-1H-benzoimidazole (42 mg, 0.29 mmol), copper(I) thiophene-2-carboxylate (9 mg, 0.048 mmol) and cesium carbonate (119 mg, 0.36 mmol) in NMP (0.5 mL) was stirred at 110° C. for 18 hours. The reaction mixture was diluted with MeOH and loaded onto an Isolute® SCX-2 cartridge (5 g). The cartridge was washed with MeOH and the desired product was eluted with 2M NH3 in MeOH. The solvents were removed and the residue was subjected to flash chromatography (Si—PCC, 0-20% MeOH in EtOAc) 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 332 as a beige solid (45 mg, 36%). LCMS (Method G): RT 7.37 min; [M+H]+ 522. 1H NMR (400 MHz, CHCl3-d): δ 8.03-7.98 (m, 1 H); 7.77-7.73 (m, 1 H); 7.32-7.24 (m, 2 H); 4.41 (m, 4H); 3.90-3.85 (m, 6 H); 3.35 (q, J=7.5 Hz, 2 H); 3.11 (m, 2 H); 2.33-2.12 (m, 2 H); 1.79 (m, 2 H); 1.57 (m, 2 H); 1.44 (t, J=7.5 Hz, 3 H); 1.34 (m, 1 H); 1.22 (s, 6 H)

Provenance & Evidence