反应详情

(1S,2S,3R,4R)-3-(2,3-Diamino-5-bromo-pyridin-4-ylamino)-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide (40.0 mg, 0.118 mmol), 4-morpholin-4-ylmethyl-benzaldehyde (26.7 mg, 0.130 mmol) and ammonium acetate (59.4 mg, 0.771 mmol) were heated in ethanol (5 mL) at 70° C. for 18 hours. The reaction mixture was concentrated and the product was purified by reverse phase chromatography (Gilson) to afford, following neutralization with saturated sodium bicarbonate solution and filtration, the title compound 35 mg (57%). mp: 217-219° C., 1H NMR (300 MHz, DMSO-d6): 13.27 (s, 1H), 8.10 (d, J=9 Hz, 2H), 8.03 (s, 1H), 7.76 (s, 1H), 7.48 (d, J=8 Hz, 2H), 7.22 (s, 1H), 7.16 (d, J=8 Hz, 1H), 6.41 (br s, 1H), 6.37 (br s, 1H), 5.23 (t, J=8 Hz, 1H), 3.59 (br s, 4H), 3.53 (s, 2H), 2.89 (s, 1H), 2.78 (s, 1H), 2.39 (br s, 4H), 2.25 (d, J=8 Hz, 1H), 1.90 (s, 1 h), 1.39 (d, J=8 Hz, 1H). MS: 523, 525 (M+H), HPLC: 1.82 min (G method).

1. concentrationThe reaction mixture was concentrated
2. customthe product was purified by reverse phase chromatography (Gilson)
3. customto afford
4. filtrationwith saturated sodium bicarbonate solution and filtration
5. custom1.82 min (G method)