Cesium carbonate → 2-(1-((5-(2-methyl-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 5-20 mL microwave vial equipped with a magnetic follower was charged with Pd2(dba)3 (28 mg, 0.03 mmol), Xphos (58 mg, 0.12 mmol), 2-[1-(5-chloro-7-morpholin-4-ylthiazolo[5,4-d]pyrimidin-2-ylmethyl)piperidin-4-yl]propan-2-ol (500 mg, 1.21 mmol), 2-methyl-1H-benzoimidazole (176 mg, 1.33 mmol), cesium carbonate (593 mg, 1.82 mmol) and dioxane (5 mL). The reaction mixture was degassed for 5 min and irradiated at 150° C. for 30 min. The reaction mixture was diluted with MeOH and loaded onto an Isolute® SCX-2 cartridge (25 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, 0-10% (2M NH3 in MeOH) in EtOAc) to give 223 as a red oil (290 mg, 47%). LCMS: (Method G): RT 6.76 min; [M+H]+ 508.4. 1H NMR (400 MHz, CHCl3-d): δ 8.10-8.05 (m, 1 H); 7.73-7.69 (m, 1 H); 7.32-7.26 (m, 2 H); 4.42 (m 4 H); 3.88 (t, J=4.6 Hz, 7 H); 3.11 (d, J=10.7 Hz, 2 H); 2.95 (s, 3 H); 2.31-2.19 (m, 2 H); 1.79 (d, J=12.7 Hz, 2 H); 1.50 (m, 2 H); 1.34 (m, 1 H); 1.22 (s, 6 H)

Provenance & Evidence