Cesium carbonate → 2-(2-methyl-1H-benzo[d]imidazol-1-yl)-4-morpholino-6-((3-morpholinoazetidin-1-yl)methyl)furo[3,2-d]pyrimidine

Participants

Reaction Steps

A mixture of 2-chloro-4-morpholin-4-yl-6-(3-morpholin-4-ylazetidin-1-ylmethyl)furo[3,2-d]pyrimidine (100 mg, 0.25 mmol), 2-methyl-1H-benzoimidazole (38 mg, 0.29 mmol), Pd2dba3 (12 mg, 0.013 mmol), Xphos (13 mg, 0.027 mmol) and cesium carbonate (184 mg, 0.56 mmol) in DMF (2.2 mL) was purged with argon gas then subjected to microwave irradiation at 145° C. for 30 min. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge (10 g), which was washed with MeOH/DCM before the desired product was eluted with 2 M NH3 in MeOH/DCM. The product was collected and concentrated in vacuo. The resultant residue was purified by flash chromatography (Si—PPC, DCM:MeOH 100:0 to 97:3 to 95:5 to 90:10) to afford 242 as a tan solid (37 mg, 30%). LCMS (Method G): RT=4.85 min, M+H+=490. 1H NMR (CDCl3, 400 MHz) δ 7.99 (m, 1H); 7.70 (m, 1 H); 7.26 (m, 2 H); 6.72 (s, 1 H); 4.07 (t, J=4.7 Hz, 4 H); 3.90-3.79 (m, 6H); 3.75 (m, 4 H); 3.64 (m, 2 H); 3.17 (m, 1 H); 3.11 (m, 1 H); 2.89 (s, 3 H) and 2.37 (m, 5 H)

Provenance & Evidence