反应详情

To a magnetically stirred solution of 6 mgs of 1-methyl-4-(2-carboxyethyl)-7-(5-amino-1-pentynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione trifluroacetate (0.017 mmol) in 1.0 mL 10% potassium bicarbonate was added 31.0 mgs of formamidine sulfonic acid (0.25 mmol). After 30 minutes, the reaction mixture was quenched with 0.5 mL acetic acid and concentrated in vacuo. The resulting residue was diluted with 2 mL water and purified by high pressure liquid chromatography, using a 1/2" C-18 reverse-phase column, eluting with a solvent gradient of 10:90 methanol(0.1% trifluroacetic acid)/water (0.1% trifluroacetic acid), time 0 to 10 min, to 50:50 methanol(0.1% trifluroacetic acid)/water (0.1% trifluroacetic acid), time 10 min to 40 min, flow=10 ml/min (Rt =36.8 min, un detection 254 nm) to yield 4.5 mgs (67%) 1-methyl-4-(2-carboxyethyl)-7-(5-guanidino- 1-pentynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione trifluroacetate. HRMS (FAB) molecular ion m/z=386.1823 (cald. C19H24N5O4, 386.1829). 1H NMR (D2O) 7.60 (1H, d, 4JHH, Ar-H o-CON), 7.51 (1H, dd, 4JHH =2 Hz, 3JHH =8 Hz, Ar-H p-CON), 7.20 (1H, d, 3JHH =8 Hz, Ar-H m-CON), 4.05 (1H, d, 2JHH =14 Hz, NCHHCO), 3.92 (1H, m, NCHHCH2), 3.72 (1H, d, 2JHH =14 Hz, NCHHCO), 3.40 (1H, m, NCHHCH2), 3.23-3.15 (5H, NCH3, H2NC(=NH2)NHCH2), 2.58 (2H, m, CH2CO2), 2.38 (2H, t, 3JHH =7 Hz, C∫CCH2), 1.76 (2H, p, 3JHH =7 Hz, CH2CH2CH2).

1. customthe reaction mixture was quenched with 0.5 mL acetic acid
2. concentrationconcentrated in vacuo
3. additionThe resulting residue was diluted with 2 mL water
4. custompurified by high pressure liquid chromatography
5. washeluting with a solvent gradient of 10:90 methanol(0.1% trifluroacetic acid)/water (0.1% trifluroacetic acid), time 0 to 10 min, to 50:50 methanol(0.1% trifluroacetic acid)/water (0.1% trifluroacetic acid), time 10 min to 40 min, flow=10 ml/min (Rt =36.8 min, un detection 254 nm)