1,1'-Carbonyldiimidazole → 1-(7-morpholino-2-((3-morpholinoazetidin-1-yl)methyl)thiazolo[5,4-d]pyrimidin-5-yl)-1H-benzo[d]imidazol-2(3H)-one

Participants

Reaction Conditions

Reaction Steps

A mixture of N-[7-morpholin-4-yl-2-(3-morpholin-4-ylazetidin-1-ylmethyl)thiazolo[5,4-d]pyrimidin-5-yl]benzene-1,2-diamine (75 mg, 0.16 mmol) and 1,1′-carbonyldiimidazole (100 mg, 0.62 mmol) in 1,4-dioxane (1 mL) was heated at 110° C. for 3 h. After cooling to ambient temperature, the mixture was loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was then washed with methanol and the desired product was subsequently eluted using 2 M NH3 in MeOH. The product was collected and concentrated in vacuo. The resultant residue was purified by flash chromatography (Si—PPC, DCM: 2 M NH3 in MeOH 100:0 to 99:1 to 98:2) to afford 183 as a cream solid (45 mg, 57%). LCMS (Method G): RT=6.72 min, M+H+=509. 1H NMR (CDCl3, 400 MHz) δ 8.71 (s, 1 H); 7.77 (m, 1 H); 7.15-7.05 (m, 3 H); 4.42 (m, 4 H); 4.01 (s, 2 H); 3.86 (m, 4 H); 3.71 (m, 6 H); 3.15 (s, 3 H) and 2.36 (m, 4 H)

Provenance & Evidence