Trifluoroacetic acid → HCID 86694189, compound

Participants

Reaction Steps

A mixture of tert-butyl 3-(2-methoxy-3H-imidazo[4,5-b]pyridin-3-yl)azetidine-1-carboxylate (intermediate 55, 450 mg, 1.479 mmol), trifluoroacetic acid (3.29 mL, 44.4 mmol) and dichloromethane (3 mL) was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure and dried under high vacuum. The crude 3-(azetidin-3-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one (250 mg, 0.598 mmol), 1H-benzimidazole-2-carboxylic acid (97 mg, 0.598 mmol), HBTU (227 mg, 0.598 mmol), triethylamine (0.416 mL, 2.99 mmol) and dry dimethylformamide (2 mL) were added to a 50 mL round bottom flask. The reaction mixture was stirred at room temperature for 12 hours. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic extract was washed with saturated ammonium chloride and dried over magnesium sulfate before concentrating in vacuo to give the crude material as a tan solid. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (12 g, hexane to ethyl acetate gradient) to provide 3-(1-(1H-benzo[d]imidazole-2-carbonyl)azetidin-3-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one (16 mg, 0.048 mmol, 8.01% yield) as off-white solid. M+1=335.1 1H NMR (400 MHz, DMSO-d6) δ ppm 4.42 (t, J=9.29 Hz, 1 H) 4.66 (dd, J=10.27, 6.16 Hz, 1 H) 4.97-5.03 (m, 1 H) 5.21-5.36 (m, 2 H) 6.92 (dd, J=7.82, 5.28 Hz, 1 H) 7.12-7.18 (m, 1 H) 7.18-7.25 (m, 2 H) 7.44 (d, J=7.82 Hz, 1 H) 7.62 (d, J=8.22 Hz, 1 H) 7.84 (dd, J=5.28, 1.37 Hz, 1 H) 11.13 (br. s., 1 H) 13.16 (br. s., 1 H)

Provenance & Evidence